INTRODUCTION Chemical Foundations

- understand biological function & chemical structure of

biomolecules; bioenergetics (energy flow in cells)
Biochemistry
Organic Chemistry- carbon-containing compounds
- describe structure, organization, function of living organisms in Functional group- atom groups w/ characteristic physical &
molecular nature; chemical basis of life chemical property
- chemical substances & interactions/reactions in living organisms Biomolecule- polymers from monomers
- how cells manufacture molecules & how chemical reactions - protein & nucleic acid are important in life processes
maintain & support life
- cells &biomolecules rise from H2O, CH4, NH3, N2, H2

Applications in Real World

Diagnose & Monitor Diseases
- transaminase levels
- hemoglobin breakdown product (bilirubin)
- measure isoforms of Lactate dehydrogenase to find myocardial
infarctions’extent
Designer Drugs
- antibiotics, chemotherapy, protein disease
- most diseases have biochemical basis:
Health maintenance (nutrition)- vitamin, minerals, water intake
Protein Structure/Function- normal vs sickle cell hemoglobin
Alkaptunoria, albinism, pentosuria- inborn metabolism errors
Molecular Oncogene mechanisms
Contribution of Cholesterol to Heart Disease (why aspirin lower
body temp)
Industry- synthesis, detoxification
Agriculture- herbicide/pesticide; transgenic crops
Career Opportunities
Agriculture- more drought-/disease-resistant crops
Research Science
Medicine
Patent Law- assess & patent biotech inventions
Forensic Science- fingerprints
Education
Publishing- scientific/medical journals/news media
Food & Cosmetic Industry
Pharmaceuticals- vaccine, drugs
Attributes of Life
Adaptation- physiology/morphology for organism to fit in its habitat
Growth & Repair- add new tissue; replace damaged parts
Metabolism- biological & chemical activities to provide energy
Reproduction- propagation & continuance of species
Complexity & Organization
- elaborate structures needed to do specific function (complexity)
- put structures in order to function efficiently (organization)
Regulation- keep functions under control
Characteristic Size & Shape- unique morphology
Response to Stimuli- respond favorably/unfavorably to environment
Locomotion- move on its initiative
Variation & Change- no 2 organisms are alike; no one remains
Unchanged
 INTRODUCTION TO CELL Peroxisome
- enzyme for hydrogen peroxide metabolism (toxic to cell)
Classification of Living Cells
- oxidation of long chain fatty acids
Prokaryote- Archaea & Eubacteria; unicellular; some in colonies
- catalase converts H2O2 to H2 & O2
- nucleoid region: DNA is single circular strand in discrete mass
- peroxide-producing & peroxide-utilizing enzymes in one
- cytosol has granular appearance due to ribosomes
compartment protect cell from H2O2 toxicity
Eukaryote- unicellular (yeast); multicellular (fungi, plant, animal)
- 1000-10000x larger volume Cystoskeleton
- defined nucleus; extensive membrane system & organelles - cytosol [organelle-free sap; for metabolic pathways (glycolysis,
glycogenesis, glycogenolysis, fatty acid synthesis)]
Eukaryotic Organelles - microtrabecular lattice (microtubule, intermediate, & actin
Plasma Membrane
filaments) connects to all organelles
- outer in contact w/variable external env.; inner w/constant env.
- scaffolding & dynamic structure for cell morphology, motility,
- integrin (outer surface) make adhesive interactions to other cells;
intracellular transport, & division
bidirectional signalling
- protein receptors (intercellular communication)
- Cystoskeletal elements (cell shape & movement)
- semipermeable due to lipid nature
Nucleus
- Nuclear envelope (2 membranes; outer one is continuous w/ER
- Perinuclear space (continuous w/ rER lumen)
- Nuclear Pore (control molecule movement in nuclear matrix &
cytoplasm)
- Nucleolus (RNA processing for ribosome synthesis)
- Nuclear Lamina (meshwork supporting nuclear structure)
- Chromatin (DNA-protein complex)
Endoplasmic Reticulum
- extensive network of interconnecting membranes extending from
nuclear envelope to plasma membrane
- changes size & shape acc to cellular needs
- ER Lumen (synthesize new proteins)
- Rough (protein folding); Smooth (lipid synthesis)
- Cytochrome enzyme (toxic substance removal)
- form peroxisome & lysosome; Ca2+ signaling
Golgi Apparatus
- Cisternae (flattened smooth membrane); lipid movement
- works w/ER where proteins for specific destinations are made
- enzymes (transfer of carbohydrates to proteins to form glycoproteins
- Membrane vesicles (shuttle proteins/hormones in cisternae,
pinched off cisterna & fuse w/another through SNARE proteins)
Mitochondria
- synthesize 90% of required ATP; apoptosis; ROS formation, cell
signaling; has ribosomes
- double membrane (outer is smooth; inner has cisternae/folds)
- matrix (space within inner membrane; mtDNA & enzyme synthesis
for oxidation reactions)
- mitosol (where metabolic reactions for pyruvate oxidation by
glycolysis, fatty acids, AA are located)’
Lysosome
- enclosed sacs w/hydrolase; intralysosomal ph 5
- intracellular digestion (due to lysosomal membrane disruption)
- Phagocytosis (virus); Pinocytosis (fluid); Endocytosis (protein)
- digestive vacuole (secondary lysosome formed by fusion of
material enclosed in vesicle & primary lysosome)
- Autophagy (hydrolysis of cellular components)
- cause cell damage if not physically separated from lipid, protein, nucleic
acid that they’re able to attack
 WATER 2. Interactions w/ Water Influence Biomolecule Structure
- interaction w/biomolecule influence biomolecule & water structure
Biomedical Importance/Clinical Correlation
- predominant chem. Component of living organisms Covalent & Noncovalent Bonds Stabilize Biomolecules
- water balance regulation depends on: - covalent b. is strongest force holding molecules together
Hypothalamic reactions controlling thirst Biomolecules Fold to Position Polar & Charged Groups on their
Antidiuretic hormone (ADH) Surfaces
Retention/excretion of water by kidneys - amphipathic; possess charged groups & hydrophobic regions
Evaporative loss Hydrophobic Interactions
- Nephrogenic diabetes insipidus - nonpolar compounds self-associate in aqueous environment
Inability to concentrate urine/adjust to subtle changes in Electrostatic Interactions
extracellular fluid osmolarity - between oppositely charged groups; salt bridges
Due to unresponsive renal tubular osmoreceptors to ADH
Van der Waals Force
- temporary dipoles from e- rapid movement from neutral atoms
1. An Ideal Biologic Solvent
- can solvate organic/inorganic molecules due to dipolar structure & Multiple Forces Stabilize Biomolecules
form hydrogen bonds - DNA double helix structure
Water Molecules form Dipoles
- irregular, slightly skewed tetrahedron w/oxygen at center
- its strongly electronegative O2 atom attracts electrons away from H2
nuclei
- dipole (molecule w/electrical charge distributed asymmetrical
about its structure)

Water Molecules form Hydrogen Bonds

- H2 bonding influence water’s physical properties & its high viscosity,
surface tension, & boiling point
- enables water to dissolve organic biomolecules containing
functional groups which can participate in H 2 bonding
- O2 atoms of aldehydes, ketones, & amides provide lone pairs of
electrons that can serve as H2 acceptors
3. An Excellent Nucleophile - restricted CO2 exhalation (asthma, obesity, trauma-induced BP)
- product/reactant for metabolic reactions Alkalosis (bl.ph>7.45)- follow vomiting of acidic gastric contents
- metabolic reactions [attack by lone pairs of e- residing on Metabolic Alkalosis – ingesting bases; HCO3- retention
nucleophiles (e- rich molecules) upon electrophiles (e- poor atoms)] Respiratory Alkalosis- hyperventilation; fever
- water’s nucleophilic attack result to hydrolysis; water is produced
when joining monomers Henderson-Hasselbach Equation
- enzymes accelerate hydrolysis: protease (proteinamino acids); - describes behavior of weak acids & bases
nuclease (phosphoester bonds in DNA/RNA)

Buffering
- exhibited in solutions of weak acids/bases & their conjugates
- resist change in pH after addition of strong acid/base
- maximum buffering capacity occurs ±1 pH unit on either side of pKa
- biologic maintenance of constant pH involves buffering by
phosphate, bicarbonate, & proteins
Buffer Solution- weak acid/base + salt of weak acid/base
- resist pH change upon addition of small amounts of acid/base

4. Exhibit Slight & Important Tendency to Dissociate

- dissociate into hydroxide ions & protons
Acidity- proton concentration of aqueous solutions reported
through logarithmic pH scale
Buffer- maintain extracellular fluid pH (7.35-7.45)
- act as acid & base (ionization/proton transfer)
- ion (in 1 instant), part of water molecule (later)
- 1 mol water = 18g; 1 L (1000g) = 55.56 mol
- probability that H+ in pure water will exist as H+ = 1.8 x 10-9
- Kw – ion product for water; at 25oC Kw = 10-14 (mol/L)2

Low pH = high H+ ; High pH = low H+

- acids are proton donors; bases are proton acceptors
- strong acids (HCl, H2SO4) completely dissociate in low pH sol’n
- weak acids (many biochemicals) dissociate partially in acidic sol’n
- strong bases (KOH, NaOH), but not weak bases [Ca(OH) 2],
completely dissociate at high pH

5. Acid-Base Balance Disturbance in Blood

PROTEIN
- verified by measuring arterial blood pH & venous blood CO 2 content
Characteristics
- pathological condition (changes in tissue pH due to blood pH)
- Most abundant in cell next to water (15% of cell mass)
Abnormal Medical Conditions in Blood pH: human cell (9,000) & human body (100,000) proteins
All contain C, H, O, N most have S
Acidosis (bl.pH<7.35)- caused by Diabetic ketosis & lactic acidosis
Metabolic Acidosis Protein (unbranched polymer); Amino Acid (monomer)
- excess production of lactic acid/ketone bodies in diabetes &Synthesis of enzymes, hormones, tissue repair, & energy
Hypoxemia; - HCO3- loss; changes pH balance in diarrhea &Presence of nitrogen (15.4 %) sets it apart from lipids & carbohydrates
chronic renal disease Casein-phosphorus (important for infants); Hemoglobin-iron (O2 transport)

Respiratory Acidosis Amino Acids: Building Blocks

- have Amino group (-NH2) & Carboxyl Group (-COOH)
- vary in size, charge, functional group, H bonding, chemical reactivity
- 𝝰- amino acid (amino & carboxyl group attached to 𝝰-carbon) 3, Basic Group
- R group/side chains (distinguishes 𝝰- amino acids from each other)
- Standard amino acid (one of 20 𝝰-amino acid found in proteins)
4 Categories acc to Side Chain Polarity
1. Non Polar AA
- 1 (-NH2) & 1 (-COOH) group + nonpolar side chain
- hydrophobic; interior of proteins (less contact w/ H2O)
4. Aromatic G.
- 9 non polar AA; Tryptophan (water could H bond w/ NH ring)

5. Imino Group

Polar AA:
2. Polar Neutral AA Essential Amino Acids
- 1 (-NH2) & 1 (-COOH) group + polar neutral side chain Complete dietary protein
- more soluble in water than nonpolar, R group can H bond to H2O - all essential AA in same relative amounts
- 6 polar neutral AA ; neither basic/acidic - may/may not contain all nonessential AA
- animal sources (except gelatin); soy
Incomplete dietary protein
- limiting AA (missing/inadequate AA)
- plant sources; (limiting) lysine, methionine, tryptophan
Complimentary dietary protein
- 2 or more combined incomplete DP that provide adequate all essential AA
- mixed plant proteins (genetic modification increase plant protein)
3. Polar Acidic AA
- 1 (-NH2) & 2 (-COOH) group (2nd -COOH group is part of side chain)
- side chain has (-) charge (sidechain -COOH group lost its acidic H atom) Chirality of Amino Acids
- 2 polar acidic AA: aspartic & glutamic acids - 4 diff. groups attached to a-carbon atom in all standard AA (except glycine)
- proteins & amino acids are L-isomers by nature
Fischer Projection Rules
a. -COOH at top; R group at bottom
b. -NH2 at horizontal; left = L; Right = D

4. Polar Basic AA
- 2 (-NH2) & 1 (-COOH) group
- sidechain has (+) charge (N of NH2 group accepted a proton)
- 3 polar basic AA: histidine, lysine, arginine
5 Categories acc to Present Side Chains
Acid-Base Properties of Amino Acids
1. Sulfur Atoms
acidic group (-COOH) & basic group (-NH2) are present on same carbon
in a-amino acid
- (neutral solution) carboxyl groups lose protons (H+)
amino groups accept protons (H+)
2. Acidic Group zwitterion  (+) charge on 1 atom & (-) charge on another cancel out
- 3 species are in equilibrium w/ each other; equilibrium shifts w/ pH change
 loop by disulfide bond from cysteine residues
Oxytocin- regulates uterine contractions & lactations
isoelectric points- pH at which zwitterion exists
Vasopressin (ADH)- kidneys, decrease urine output, prevent dehydration
- 15 amino a. w/ nonpolar or polar neutral side chains (pH 4.8-6.3)
- 3 basic AA (higher isoelectric points); 2 acidic AA (lower isoelectric points) b. Small Peptide Neurotransmitters
Enkephalins- pentapeptide neurotransmitters, bind at brain’s receptor sites
to reduce pain
Met-enkephalin & Leu-enkephalin- only differ at amino a. at C-terminal end
-painkillers morphine based on binding at receptor sites as Enkephalins
c. Small Peptide Antioxidants
Glutathione- tripeptide, regulate redox, protect cells from peroxides &
superoxides (ROS)
- unusual feature; bonded to Cys through side chain carbonyl group
than 𝝰-carboxyl group

Cysteine- chemically unique amino acid; has sulfhydryl group (-SH) General Structure of Protein
- dimerizes w/ another cysteine to form cystine a. Acc. to Chemical Composition
- 2 cysteine residues linked by disulfide bond
Simple Protein- amino acid only; may have sub unit
Conjugated “ - more than 1 peptide chain; w/ non amino acid entities
Prosthetic group (non AA)

Peptide- unbranched chain of AA; classified by of # of AA in chain

- not yet a protein (40+ AA residues to become protein)
Di-/Tri-/Oligopeptide- 10-20 AA; Polypeptide- long unbranched chain of AA

Primary Structure
- AA sequence in peptide bonds (same wherever protein is)
- C & N atoms arranged in zigzag)
1. Peptide linkages are planar
- 2 amino a. linked through peptide linkage, 6 atoms lie in same plane:
Peptide bond- covalent bond between carboxyl group of 1 amino a. & amino a-carbon & C=O group from 1st amino acid
group of another a.; N-terminal end → C-terminal end N-H group & a-carbon atom from 2 nd amino acid
- backbone chain of protein
amino acid residue- portion of AA structure that remains after H2O release
during peptide bond formation

2. Planar peptide linkages are rigid

- rotation on C-N bond is hindered; cis-trans isomerism is possible
- trans isomer is preferred O of C=O & H of N-H are trans
Peptide Nomenclature:
Secondary Structure
Rule 1: C-terminal amino acid residue keep its full name
- H bonding between Carbonyl’s O atom of peptide linkage & Amino’s H atom
Rule 2: Other AA residue end in -yl except (tryptophyl, cysteinyl, glutaminyl
Asparaginyl) - H bond can be 2 segments from diff. backbone/same backbone that folded
Rule 3: AA naming sequence begins at N-terminal end
back upon itself
a. Glu-Ser-Ala = Glutamylserylalanine - (α-helix) / (β-pleated sheet) found only in protein portions where amino
b. Gly-Tyr-Leu-Val = Glycyltyrosylleucylvaline acid R groups present are small
- large R groups disrupt both types of secondary structure
Biochemically Important Small Peptide 2 types
a. Small Peptide Hormone α-helix
- nonapeptide; 6 residues held in form of 1. COIL/SPIRAL; clockwise turn
 2. H bond between C=O & N-H are parallel to axis of helix
3. H bond involves C=O & N-H group of amino acid four AA residues along
spiral; 1 turn of spiral = 3.6 amino acid residue
4. AA R groups extend outward from spiral, no room for R group within
β-pleated sheet
- 2 extended protein segments in same/diff molecules
- intrachain (single chain folds back to itself) / interchain (diff. peptide chain)
- in molecules where β-pleated sheet involves single molecule, U-turns are
needed to form structure
- PLANAR; zigzag structure
1. H bond between C=O & N-H lie in sheet’s plane
2. AA R group found on top/bottom, above/below sheet’s
Unstructured segments -has neither (α-helix) or (β-pleated sheet) Quaternary Structure
- multimeric proteins, subunits independent, not covalently bonded
- organization among peptide sub units on multimeric proteins
- dimer (2 subunits); tetramer (4 subunits)
- non covalent interactions, most importantly Hydrophobic interactions

Tertiary Structure
- 3D shape from interaction of R groups
Interactions:
1. Disulfide Bonds- strongest bond; -SH of 2 cysteine form covalent bond
- intramolecular / intermolecular
2. Electrostatic Interaction (Salt Bridges)
- acidic & basic R groups; at diff. pH carry charges -COO- & NH3+
- cation & anion
3. Hydrogen Bonds- in AA w/polar R groups; weak, disrupted by pH changes
4. Hydrophobic interactions
- 2 non polar side chains, polar group outward (toward solvent),
nonpolar side chains inward & interact;
- London dispersion between alkyl & phenyl
- weaker than H bonds/electrostatic but significant due to number
Protein Hydrolysis
- when protein in solution of strong base & strong acid is heated,
peptide bonds are hydrolyzed & produce free amino acids
Complete PH (all peptide bonds are broken; AA are only products)
Partial PH (some peptide bonds are broken; produce AA & small peptides)
Protein Denaturation 8. Storage “ - bind & store molecules for future use (ferritin)
- partial/complete disorganization of 3Dstructure 9. Nutrient “ -important in early stages of life (Casein)
- disruption of secondary, tertiary, & quaternary structural interactions 10. Regulatory “- binding site for messenger proteins & enact function
- cannot affect primary structure 11. Buffer “ – acid-base balance in body
- protein’s biochemical function depends on 3D structure (loss of function) 12. Fluid-balance “ - maintain fluid balance between blood & tissue
- renaturation (refold 3D structure); extensive denaturation is irreversible (albumin, globulin in capillary beds)
- loss of water solubility (consequence); coagulation (precipitation)
Ex: albumin (egg white), enzymes inactivated at 41 ºC Glycoprotein
Curdy casein precipitate (milk). - conjugated proteins; contain carbohydrates/carb derivatives & amino acids
- pure alcohol quickly denature & coagulates bacterial surface, creating a Collagen- attached sugar units by glycosidic linkages; related to cross linking
barrier to prevent further penetration - collagen fibrils (direct assembly of helices into complex aggregations)
- 70% alcohol denatures more slowly, allowing complete penetration before Immunoglobulin - protective response to foreign invasion
coagulation of surface - antigen (foreign substance vs. antibody)

Protein Classification based on Shapes

Fibrous Protein
- w/ elongated shape & 1 dimension; longer
- linear; form aggregate to form macromolecular structure
- water insoluble; single secondary structure type; structural function &
external protection
- present more in humans than globular
Collagen Lipoprotein
- most abundant protein in humans (30% of total body protein)
- conjugated proteins composed of lipids & amino acids
- major structural material in tendons, ligaments, blood vessels, skin
- classified based on density
- rich proline content = triple helix conformation
- plasma lipoprotein (transport system for lipids in bloodstream)
- form fibrils w/ cross linking on helices; skin stiffening (aging)
α-Keratin 1. Chylomicrons- transport dietary triacylglycerols (intestine to liver to adipose)
- major part of hair, feather, wool, finger/toenails, claws, scales, horns, turtle 2. Very-low-density lipoprotein (VLDL)- transport triacylglycerols from liver to
shells, quills, hooves adipose tissue
- coiling at higher levels produce strength, intercoil disulfide bridge 3. Low-density “ (LDL)- transport cholesterol from liver to cells
4. High-density “ (HDL)- collect excess cholesterol from body tissues &
transport it back to liver for degradation to bile acids

Globular Protein
- peptide chains folded into spherical/globule shapes
- hydrophilic side chains on outside; hydrophobic in interior
- water soluble; several secondary structure types; metabolism
- more types than fibrous
Hemoglobin
- transports oxygen from lungs to tissue
- Tetramer (4 peptide chains each contain heme group = binds to O2)
- Fe atom at center interact w/ O2 ; 1 hemoglobin = 4 O2 molecules
Myoglobin
- oxygen storage molecule in muscles (working muscles)
- single peptide chain & a heme unit hence carry 1 O2
- higher affinity for O2 than hemoglobin

Protein Classification based on Function ENZYMES

1. Catalytic proteins- biochemical catalysts (enzymes) Importance
2. Defense “ - immunoglobulins/antibodies fxn in immune system metabolism, diagnosis, therapeutic (digestive enzymes)
3. Transport “ - bind to small biomolecules & transport (hemoglobin) - enzyme level in blood is an indicator in disease (myocardial infarction)
4. Messenger “ - transmit signals to coordinate biochemical processes - biological catalysts (increase rate of reaction by looking for alternative
between cells, tissues, organ (Hormones) pathway w/low activation energy)
5. Contractile “ – movement; filament-like proteins in muscles, sperm Characteristics
flagella
6. Structural “ - stiffness & rigidity (Collagen, keratin) - not altered/consumed during reaction; reusable (recovered after use)
7. Transmembrane “ – in cell membrane; control movement - show specificity to reaction they control
- sensitive to environment; controlled by adjusting temp, pH, substrate HYDROLASE
concentration - HYDROLYSIS reaction (water is acceptor of transferred group)
Structure - protein hydrolyzing (Peptidase), Carbohydrase (amylase, maltase, lactase),
Lipid hydrolyzing (Lipase), Deaminase, Phosphatase
- globular; complex 3D
SIMPLE- protein only; readily activated w/o activator
CONJUGATED/HOLOENZYME- protein+nonprotein; w/ cofactor; activated
a. Apoenzyme- protein part; inactive
b. Cofactor- nonprotein part; required for catalysis
LYASE
1. Prosthetic Group- small inorganic molecule/atom; metallic
ions/minerals (zinc, manganese, iron) - cleave bonds by means other than hydrolysis & oxidation
- charged, tightly bound to apoenzyme by ES interaction add H2O, ammonia, CO2 across double bonds/remove these elements to
-
produce double bonds
2. Coenzyme- large organic molecule; vitamins
- Fumarase, Carbonic anhydrase, Hydratase, Dehydratase
- loosely bound to apoenzyme by intermolecular force
Active site- small enzyme region where substrate attaches
Substrate- reactant in chemical reaction; reacted upon by enzyme

ISOMERASE
- ISOMERIZATION reaction (L to D isom.; Mutase reaction/shift of chem. group)
- transfer within molecule (not between molecules)
- Isomerase, Mutase

Naming Enzymes
- suffix -ase (sucrase- catalyze sucrose hydrolysis)
LIGASE
- enzyme function (oxidase- oxidation reactions)
- common names used for digestion enzymes (pepsin & trypsin) - LIGATION reaction (join 2 molecules w/ covalent bond)
- 2 chemical groups are joined/ligated w/ ATP
- substrate & its function (alcohol dehydrogenase- oxides ethanol)
- Acetyl-CoA Carboxylase, Glutamine synthetase
Classification
- 6 functional classes (EC number Classification) by Int’l Union of Biochemists
(IUB) on Basis of Types of Reactions they catalyze
EC 1. Oxidoreductase EC 4. Lyase
EC 2. Transferase EC 5. Isomerase
EC 3. Hydrolase EC 6. Ligase
Enzymatic Action
- each enzyme has classification number w/4 digits
- chem. reactions need activation energy (initial energy input)
- ex: EC: (2.7.1.1) HEXOKINASE
- molecules are in transition state (no longer a substrate but not yet a product)
2. = class (Transferase) - biological systems are very sensitive to temp changes
7. = subclass (Transfer of Phosphate)
- enzyme increase rate of reaction w/o increasing temp by lowering activation
1. = sub-sub class (Alcohol is phosphate acceptor)
energy, looking for new reaction pathway (“shortcut”)
1. = specific name (ATP, D-HEXOSE-6-PHOSPHOTRANSFERASE)
- enzyme-controlled reactions are 108-1011x faster than nonenzymatic ones
OXIDOREDUCTASE
- REDOX (Oxidation- O2 addition, H+ removal; Reduction- O2 removal, H+ add.)
- Glucose Oxidase, Peroxidase, Catalase, Phenylalanine hydroxylase

TRANSFERASE
- TRANSFER reactions (between molecules)
- Transaminase (ALT & AST), Phosphotransferase (Kinase), Transmethylase,
Transpeptidase, Transacylase
 2. pH
- slight differences from optimum value cause small changes in enzyme
charges & its substrate’s molecule
Enzyme-Substrate Binding - ionization change affect substrate binding w/ active site
2 models: - diff. optimum pH where enzyme activity is at its highest
LOCK-AND-KEY MODEL- active site has rigid shape; substrate w/same - extreme pH changes cause denaturation
shape can fit (“substrate is key that fits active site’s lock”)

3. Substrate Concentration
- ↑ reaction rate = ↑ substrate conc (at constant enzyme conc)
- max activity occur when enzyme is saturated (all enz bound to substrate)
= saturation point
- altering enzyme conc also changes Vmax
INDUCED-FIT MODEL- active site is flexible, not rigid, can change its shape
4. Enzyme Concentration
- enzyme shape, active site, & substrate adjust to maximize fit
which improves catalysis - ↑ reaction rate = ↑ enzyme conc (enzyme conc. is lower than substrate)
- greater range of substrate specificity
- model is more consistent w/ wider enzyme range

b. COFACTORS & COENZYMES

1. Cofactor- additional nonprotein needed by enzyme for proper functioning
- vitamins (unspecific to which enzyme they assist)
Cu2+- assist oxidase (last enzyme in respiratory electron transport chain)
Fe2+ & Fe3+ - help catalase; convert H2O2 to water & oxygen
Mg2+- assist glucose-6-phosphate in glycolysis
Enzyme Specificity Mn2+- help arginase (final enzyme in urea cycle)
Zn2+- assist alcohol dehydrogenase w/NAD+ to convert alcohol to
aldehyde & carboxylic acid
2. Coenzyme:
NADH (Vit B3)/nicotinamide adenine dinucleotide
- carry & transfer electrons; functions as oxidizing agent in redox
FADH (Vit B2)/flavin adenine dinucleotide
- reducing agent in cell. resp.; donates e- to electron transp. chain
Quinone- fully conjugated aromatic rings acting as pigments in
bacteria, fungi, plants
CoA- acyl group carriers to transport functional groups (Acetyl CoA)
- synthesized from Vit B5
Factors affecting Enzyme Activity Others:
a. ENVIRONMENTAL CONDITION Vit C/Ascorbic acid- co-substrate w/iron in forming collagen
1. Temperature - helper of vit E & B9 to remain active
- increase enzyme activity to its optimum temp /Vit B1/thiamin pyrophosphate- needed in CAC (carboxyl group transfer)
- optimum temp (temp at which enzymatic reaction occur fastest)Vit(40Bo6Ccompounds- coenzymes for amino group transfer
o
- many enzymes are at lower temp (coldwater fish die at 30 C sinceBiotin
their (Vit B7 or Vit H)- carboxyl group transfer
o
enzymes denature; few bacteria have enzymes that withstand 100/Vit C) B9/tetrahydrofolate- methylation reactions
o
- most enzymes fully denature at 70 C Cobalamin/Vit B12- methyl group transfer
Vit A, K - reversed by increasing substrate conc.

Oxidative Phosphorylation System

2. Noncompetitive “ - structure diff. from substrate (REVERSIBLE)

- distorts enzyme shape so substrate can’t bind to active site
- inhibits by binding reversible/irrevers. at allosteric site

c. ALLOSTERIC REGULATION (Positive & Negative regulation)

1. Neg. Regulator-Inhibitor- decrease enzyme reaction rate
- changes active site so substrate is less readily accepted
2. Pos. Regulator-Activator- increase enzyme reaction rate
- change active site shape so it can readily accept substrate

3. Uncompetitive “- structure diff. from enzyme (IRREVERSIBLE)

- happens only when enzyme is already bound to substrate
- substrate conc is reduced at same time w/ enzyme action rate
(substrate binds longer in enzyme)
- inhibits by binding irreversibly to enzyme but not at active site

3. Feedback Control- activation/inhibition of 1st reaction in reaction sequence

is controlled by product of reaction sequence
- end product binds at allosteric site on
pathway’s 1 st enzyme

Application: Poison- snake bite, plant alkaloid, nerve gas

Medicine- antibiotics, sulphonamides, sedative, stimulants
Aspirin (inhibit prostaglandins synthesis responsible for
arthritis pain)
Methotrexate (in cancer chemo to semi-selectively inhibit
DNA synthesis of malignant cells)
Sulfa drugs (inhibit folic acid synthesis for metabolism &
growth of disease-causing bacteria)

d. ENZYME INHIBITORS
Inhibitor- reduce rate of enzymatic reaction; specific; work at low conc. VITAMINS
- block enzyme but don’t destroy it; reversible/irreversible General Characteristics
- drugs & poisons in nervous system
Mode of Actions:
1. Competitive Inhibition- compete w/substrate for active site (REVERSIBLE
- inhibitor’s action is proportional to conc.
- closely resembles substrate’s structure
 - coenzyme; DNA synthesis; anticancer drug methotrexate
- homocysteine metabolism; neurotransmitter formation

VITAMIN B12
- has mineral cobalt; synthesized by bacteria, fungi, lower organisms
- involved in folate metabolism; RBC formation; myelin sheath maintenance
- pernicious anemia (nerve degeneration & paralysis)

VITAMIN A
- primary alcohol of Retinol (C20H30O) only in animals, sourced in cod liver oil,
VITAMIN C
fish-liver oils, animal liver, dairy products
- co-substrate to form collagen; collagen has hydroxylysine & hydroxyl proline
- provitamin A found in plants in form of carotene (provitamins have no
- lysine & proline hydroxylation in forming collagen are catalyzed by enzymes vitamin activity however after ingestion in diet)
requiring Vit C & iron
- needed for vision, regulating cell differentiation, epithelium health
- in V.C deficiency, hydroxylation is impaired; collagen’s triple helix is maintenance, reproduction, growth
unassembled: SCURVY (skin lesions, fragile blood v, loose teeth, bleeding gums)
- involved in metabolism of certain AA VITAMIN D
- “Antirachitic vitamin”; for normal calcification of bone tissue
B COMPLEX VITAMINS
- controls ratio of Ca & P for bone mineralization/hardening
- coenzymes (active enzymes); act together in metabolism - 2 forms active in body: ergocalciferol (D2) & cholecalciferol (D3)
- metabolic pathways used by protein, carbo, fat; found in same food - not required in humans exposed to sunlight year-round
- single deficiency rare; broken down from coenzyme form into free vitamins in
stomach & small intestine VITAMIN E
- absorbed primarily in small intestine (50-90%) - “Antisterility vitamin”; most active biological form: α-Tocopherol
- once inside cells, coenzyme forms are resynthesized - Tocopherol (Gk: “Promoter of Childbirth”) functions as antioxidant by
- no need to ingest coenzyme forms since we can make them inhibiting oxidation of unsaturated fatty acids by O2
- antioxidant—protects against oxidation of other compounds
THIAMIN / B1
- has sulfur & nitrogen group; destroyed by alkaline & heat VITAMIN K
- coenzyme: releases energy from carbo; CO2 is released from larger molecule, - synthesized by bacteria in colon
glucose metabolism - active in protein formulation in regulating blood clot
- thiamin deficiency affect alcoholics since thiamin absorption & use are - deficiency occur during 1 st days after birth since newborns lack intestinal
diminished & excretion is increased by alcohol consumption bacteria that produce V.K/no V.K storage or during after antibiotic therapy that
sterilizes light
RIBOFLAVIN
- 2 coenzymes: flavin adenine dinucleotide (FAD) & flavin mononucleotide
- involved in energy-yielding metabolic pathways
- fatty acids broken down & burned for energy

NIACIN / B3
- coenzyme forms: nicotinic acid & nicotinamide
- needed when cell energy is utilized
- required in synthetic pathways (fatty acid synthesis)

PANTOTHENIC ACID
- part of coenzyme-A; essential for CHO, fat, protein metabolism
- rare deficiency since it’s usually combined w/other deficiencies
- no known toxicity

BIOTIN
- free & bound form; CHO & fat metabolism
- assist in CO2 addition to other compounds
- synthesis of glucose, fatty acids, DNA; help break down AA

PYRIDOXINE / B6 CENTRAL DOGMA

- DNA instructions are converted to functional products
- 3 compounds; coenzyme; activate enzymes for CHO, fat, protein metabolism
- synthesize nonessential AA via transamination, neurotransmitters,
hemoglobin & WBC A. DNA REPLICATION/SYNTHESIS
- homocysteine; produce toxic effect on arterial walls (atherosclerosis)- exact copy of parental DNA is synthesized using parental DNA’s
- metabolized by Vit B6, B12, & folate polynucleotide strands as template
a. Unwinding of double helix by helicase
FOLATE b. Polymerization of nucleotide components to form new daughter strands
 c. Formation of 2 new DNA helices each w/1 parent & 1 daughter LEADING LAGGING
strand - binds w/ RNA primers (made by
- primer (short RNA produced by primase; primase) at various points
Characteristics starting point for synthesis) binds to
strand’s end in 5’- 3’ - Okazaki fragments are added to this
a. Semiconservative- occurs in Synthesis/S phase before cell division strand between primers in 5’- 3’
- “way by DNA copies are produced is similar in all organisms” - DNA polymerase make new
b. Bidirectional- several origins; 2 forks per origin complementary nucleotide bases & new
strand (elongation)
- (eukaryotes) polymerase α, δ, ɛ primary
polymerases in replication
- continuous replication - discontinuous replication
lagging strand (5’- 3’ ; away from replication fork)

2. ELONGATION
- DNA polymerase (carries out replication) acts only in 5'-3'; daughter strand is
replicated through Okazaki fragments.
3. TERMINATION
Features - after forming con/discontinuous strands, exonuclease removes RNA primers
a. Timing of Replication: limited to S phase from original strands. Gaps are filled by more complementary nucleotides
b. Replication Rate: ≈ 50 nucleotides/second per replication fork - another enzyme “proofreads” newly formed strands to avoid errors
c. Replicons: replicated DNA is controlled of single origin - DNA ligase joins Okazaki fragments together to form single unified strand
: they compress replication of large genomes into short periods - telomerase (special DNA polymerase) catalyzes synthesis of telomere
d. Okazaki fragments: DNA segments formed on discontinuous replication of sequences at DNA’s ends
1 DNA strand as other strand in continuous replication - parent strand & its complementary DNA strand coils double helix shape

Enzymes in Replication
a. Helicase- separates DNA strands
b. RNA primase- catalyzes RNA primer synthesis; attach RNA primer
c. DNA polymerase III- synthesis of new strand
d. DNA Polymerase I – replaces RNA primer w/ DNA (after replication)
e. DNA ligase- links Okazaki fragments, sealing lagging strand (base modific) B. RNA SYNTHESIS/TRANSCRIPTION
- single stranded RNA w/ base sequence complimentary to DNA strand
template is synthesized
- major control point in gene expression & protein production
a. RNA Polymerase I- nucleolus; transcribes 28S, 18S & 5.8S rRNA genes
b. RNA P II- nucleoplasm; transcribes mRNA from protein coding genes & small
nuclear RNA (snRNAs) in mRNA processing
c. RNA P III- nucleoplasm; transcribes genes for tRNA, 5S rRNA, 1 snRNA, & 7S
RNA associated w/signal recognition particle (SRP) in protein translocation
across ER membrane

Features
a. RNA Polymerases catalyzes process & 6 general transcription factors
Challenges
b. ATP, GTP, CTP, UTP, & Mg2+ is required
a. Separate 2 strands: c. Primer isn’t needed, only DNA template
- strand is unwound & protect unwound part from nucleases which attacks
d. Read from 5’ - 3’
single stranded DNA
e. Template is unchanged
b. Synthesis of 2 DNA strand from 5’ to 3’ end:
- lagging strand is also 5’-3’ which is hard to produce anti-parallel strand
c. Guard against error in replication:
- how to ensure correct base is added in each base sequence
Steps
Steps
1. INITIATION
1. INITIATION
- helicase breaks H-bond that creates Y shape (replication fork)
RNA polymerase binds gene’s promoter (turn off/on gene; 35 nucleotides). This
- single-stranded DNA Binding Protein (SSB Protein) binds to now single-stranded
signals DNA to unwind so enzyme can ‘‘read’’ bases from 3'-5' of template strand
DNA to prevent separate strands from joining again
- leading strand (3’- 5’ ; towards replication fork) 2. ELONGATION
- RNA polymerase reads unwound DNA strand & builds mRNA using
complementary base pairs. There’s brief time during this when newly formed
RNA is bound to unwound DNA. During this process, Adenine in DNA binds to NUCLEIC ACIDS
Uracil in RNA
- nucleus; DNA & RNA; building block of nucleotides
3. TERMINATION 3 parts:
- RNA polymerase crosses a stop sequence in gene. mRNA strand is complete & Heterocyclic base- Purine (A, G); Pyrimidine (C, T, U)
detaches from DNA. - DNA (A-T; C-G); RNA (A-U; C-G)
Sugar- pentose (5-carbon): deoxyribose & ribose Nucleoside
Nucleotide
Phosphoric acid
C. PROTEIN SYNTHESIS/TRANSLATION
Bond between Base & Sugar
- code carried by mRNA directs polypeptide synthesis using ribosomes & cells
- sugar’s Carbon 1 joined to base via one of its N atoms
- protein coding genes is discontinuous
- genetic info translation to polypeptide primary sequence Pyrimidines: via N-1 position Purines: via N-9 position
- exons (gene’s coding sections); introns (DNA’s noncoding sections)

GENETIC CODE BOOK- coding dictionary specifying meaning for base sequence
Codon- mRNA triplet base sequence
- AUG (initiating/start codon) (codon for METHIONINE as start signal)
- 64 possible trinucleotide sequences; 61 code for AA
- UAA, UAG, & UGA (3 stop codons/polypeptide chain terminating)
Deoxyribose Ribose

Anticodon- tRNA 3-base sequence; interacts w/ codon of mRNA

- given in 5’ - 3’ like codon
 base pairing between anticodon & codon is responsible for actual translation Nucleosides
of structural genes’ genetic info RNA: ribonucleoside DNA: deoxyribonucleoside
Adenosine deoxyadenosine
Properties
guanosine deoxyguanosine
a. Degenerate- any coding system where signals have same meaning cytidine deoxycytidine
b. Specific- each codon is a signal for specific AA uridine deoxythymidine
c. Nonoverlapping & w/o Punctuation
Nucleotide
- mRNA coding is read by ribosome from initiating codon (AUG) as continuous
sequence taken 3 bases at a time until stop codon is reached - phosphate ester of nucleoside
- reading frame: set of contiguous triplet codons in mRNA - phosphate group joined to nucleoside at hydroxyl group attached to sugar’s
- open frame: series of triplet base sequence in mRNA w/o stop codon C-5 (nucleoside)
e. Universal- coding signals for AA are always same. - 5’-phosphate / 5’-nucleotide (primed number=sugar’s atom where phosphate
is bonded)
Steps
1. INITIATION
- small ribosomal subunit binds mRNA then anticodon of specific tRNA (initiator
tRNA) base pairs w/ initiation codon AUG
- ends when large ribosomal subunit combines w/ small subunit
2 sites on complete ribosome for codon-anticodon interactions:
a. P (peptidyl): occupied by initiator tRNA RNA: Adenosine 5’-triphosphate (ATP) / adenylic acid (A)
b. A (aminoacyl) Guanosine “ “ (GTP) / guanylic acid (G)
Cytidine “ “ (CTP) / cytidylic acid (C)
2. ELONGATION Uridine “ “ (UTP) / uridylic acid (U)
- polypeptide is synthesized acc genetic message specifications
DNA: Deoxyadenosine 5’-triphosphate (dATP)
- message is read in 5’ - 3’ direction
nd
Deoxyguanosine “ “ (dGTP)
- begins as 2 aminoacyl-tRNA binds to ribosome in A site due to Deoxycytidine “ “ (dCTP)
codon-anticodon interactions
Deoxythymidine “ “ (dTTP) / thymidylic acid (T)
- peptide bond formation is catalyzed by peptidyl transferase where α-amino
group of A site AA attacks carbonyl group P site AA, making AA attached to
A site tRNA; now, uncharged P site tRNA is released from ribosome
Translocation- ribosome is moved along mRNA not part of chain:
- Elongation Cycle (steps repeated until stop codon enters A site) AMP, ADP, ATP
- as mRNA moves, next codon enters A site & tRNA w/ growing peptide - additional phosphate groups can be added to
chain moves into P site nucleoside 5’- monophosphates to form di- &
triphosphates (ATP- major energy source in cell)
3. TERMINATION DNA vs RNA
- polypeptide chain is released from ribosome wherein protein releasing
factor binds to A site
- translation terminates since a stop codon can’t bind an aminoacyl-tRNA. It
ends as ribosome releases mRNA & dissociates into large & small subunits.
Fragment of DNA/RNA Chain

DNA Structure
Watson-Crick Model- double helix; stabilized by H-bonds
- sugar & phosphate is backbone; bases form connecting link
3 types
A-DNA B-DNA Z-DNA
PITCH 2.8 nm 3.4 nm 4.5 nm
Bp/REPEAT 11 10 12
TWIST/bp 33.6o 35.9 30o
Bp TILT 19o 4.1o 7o
Nucleic acid backbone: ...- phosphate – sugar – phosphate – sugar - …
- 1st nucleotide has 5’ phosphate not bonded to other nucleotide; last - 3D helix structure discovered by Watson-Crick
nucleotide has free 3’ hydroxyl - has 2 strands wound round each other to form double helix (1 turn has
- polarity in nucleotide: they have a 5’ & 3’ ends 10.4 base pairs) w/bases on inside & sugar-phosphate on outside
- each nucleotide cis 1st letter of base; creating base sequence written in- 2 strands are organized in antiparallel arrangement running in opposite
5’ → 3’ direction direction (1 strand is 5’-3’, other is 3’-5’)
5’ 3’ 5’ 3’ - (eukaryote) DNA is stored in nucleus separated by semipermeable membrane
Ex: ACTTTCAGACCTG (single DNA strand); GUCAAGCCGAUC (RNA strand)
- only organized into chromosomes during cell replication
Levels of Nucleic Acid Structure - between replications, it’s stored in compact ball (chromatin) wrapped around
PRIMARY- nucleotide/base pair sequence in polynucleotide chain bonded by histones to form nucleosomes
phosphodiester bond
Complimentary base pairing: A-T (2 H-bonds) C-G (3 H-bonds)
- read from free 5’-end using base’s letters (5’—A –C –G –T –3’)
nucleic acid polymer- free 5’-phosphate group & 3’-OH group on either ends
Factors making DNA Stable
1. Covalent bonds linking individual nucleotide subunits (not susceptible to
hydrolytic cleavage)
2. Noncovalent interactions (hydrophobic inter, H-bonds, electrostatic inter)
3. Planar structure of bases
4. Base stacking
5. Positive reactions between DNA & proteins

Types of RNA (product of DNA Transcription)

TRANSFER RNA (tRNA) / soluble RNA
- holds specific AA for incorporation into a protein molecule
SECONDARY- 3D conformation of backbone (H-bond) - smallest RNA (size 73 & 93 nucleotides, average 75); warped cloverleaf shape
- base pairing of complimentary nucleotides of nucleic acid
RIBOSOMAL RNA (rRNA)
TERTIARY- supercoiling of molecule that accommodates steric & geometric
- combines w/ protein to form ribosome
constrains; atom arrangement in space (intermolecular force)
- nucleoprotein (eukaryotic ribosomes have 60S & 40S subunits)
- most abundant, 80% of total RNA (guanylic acid is most abundant)
- initiates synthesis of polypeptides in ribosome

QUATERNARY- nucleic acids interaction/relationship to other molecules MESSENGER RNA (mRNA)

- transmission of genetic info from DNA to site of protein synthesis
- unstable, short-lived product in cell (5% of cellular RNA)
- its nucleotide sequence is complimentary to base sequence in template DNA
hRNA
- precursor of mRNA, found in cell nucleus

Eukaryotic Chromosome Structure CARBOHYDRATES

- most abundant; made of C, O, H; (C•H2O)n where n ≥ 3
- they’re polyhydroxy aldehyde/polyhydroxy ketone (hydroxy, ketone, aldehyde)
Function  mutarotation- 2 anomers can freely interconvert in solution
- provide energy (only glucose is converted to energy); storage (glycogen/reserve)
- biomolecule synthesis (provide carbon); part of nucleic acid structure
- component of cell membrane (w/lipids) (glycolipids)
- cell-cell & cell-molecule recognition processes (w/proteins) HAWORTH PROJECTION
- 5- & 6-membered hemiacetals represented
Classification as planar pentagons/hexagons that may
1. Monosaccharide- smallest, 1 unit of polyhydroxy aldehyde/polyhydroxy ketone be viewed through edge
- water-soluble (polar) - for monosaccharide that underwent chem reaction
2. Disaccharide- 2 mono bonded by glycosidic bond (covalent); water-soluble
3. Oligosaccharide – 3-10 mono; commonly found in conjugated biomolecules
4. Polysaccharide – hundreds to 50,000 units

MONOSACCHARIDES
a. acc to NUMBER OF CARBON ATOMS
triose C3 H6 O 3 pentose C5 H1 0 O5 heptose C7 H1 4 O7
tetrose C4 H8 O 4 hexose C6 H1 2 O6 octose C8 H1 6 O8
b. acc to FUNCTIONAL GROUP: aldose (aldehyde group); ketose (ketone group)
general formula:

Simplest aldose & ketose

Glucose vs. Fructose

FISCHER PROJECTION- 2D form for showing configuration of tetrahedral stereocenters

D & L- acc to conventions by Fischer

GLUCOSE- aka dextrose/blood sugar; large quantities in living world
D-monosaccharide- as Fischer projection, -OH on its penultimate carbon on right
- primary fuel; preferred source of brain cells & cells w/few/no mitochondria
L-monosaccharide- -OH on its penultimate carbon on left
- large amounts generate energy in cells w/limited O2 (eyeball)
- dietary sources: starch & disaccharides (lactose, maltose, sucrose)
FRUCTOSE- aka levulose/fruit sugar; found in vegetables & honey
Enantiomers & Diastereomers - sweetest sugar, twice as sweet as sucrose; sweetening agent in food
Enantiomers- stereoisomers; mirror images - large amounts are used in male reproductive tract (synthesized in seminal
(ex: D-glucose & L-glucose) vesicles & incorporated into semen, sperm use fructose as energy)
Diastereomers- not mirror images
GALACTOSE- synthesize lactose; glycolipids, some phospholipids, proteoglycans, &
(ex: D-ribose & D-xylose)
glycoproteins; readily synthesized from glucose-1-phosphate
Epimers- diastereomers that differ at 1 asymmetric carbon (ex: Dglucose & D-galactose) - attached to blood typing
Reactions of Monosaccharides

REDOX

Ex: glucose to sorbitol (alcohol)

Cyclic Carbohydrates- monos have -OH & C=O groups in same molecule
- exist almost entirely as 5- & 6-membered rings
GLYCOSIDE FORMATION
anomeric carbon- new stereocenter from cyclic formation
anomers- carbohydrates that differ in configuration only at anomeric carbons
Ex:
PHOPHATE ESTER FORMATION

Ex:

GLYCOSIDIC BOND POLYSACCHARIDES

- bond from anomeric carbon to -OR group a. STORAGE:
Glycoside- carbohydrate where -OH of anomeric carbon is replaced by -OR STARCH- principal food reserve in plants; polymers of α-Dglucose units
Furanosides- derived from furanoses GLYCOGEN & AMYLOPECTIN- animals
Pyranosides- derived from pyranoses bush-like w/ α(1→6) branch points: every 24 to 30 glucose residues (amylopectin)
every 8 - 12 glucose residues for (glycogen)

DISACCHARIDES

b. STRUCTURAL:
CELLULOSE- 1/3 of plant biomass; most abundant organic substance on earth
- indigestible to humans; digested by ruminant animals using cellulase
MALTOSE- aka malt sugar; intermediate product of starch hydrolysis
- D-glyucopyranose residues linked by β(1,4)-glycosidic
- α(1,4) glycosidic link between 2 D-glucose molecules
CELLOBIOSE- degradation product of cellulose
- 2 molecules glucose linked by β(1,4) glycosidic bond
LACTOSE- aka milk sugar; 1 molecule galactose’s OH on C1 linked by βglycosidic to
1 molecule glucose’s OH of C4 of 1
SUCROSE- aka table, cane, beet sugar; produced in plants’ leaves & stems
- α,D-glucose & β,D-fructose residues linked by glycosidic bond in both anomeric
carbons

OLIGOSACCHARIDES- monosaccharide arrangement determines blood type

CHITIN- like cellulose in its biological function & primary, secondary, tertiary structure
- fungi walls; exoskeletons of crustaceans, insects, spiders
- extended ribbon; identical to cellulose except that -OH group on each C-2 is
replaced by -NHCOCH3 (repeating units are Nacetyl-D-glucosamines in β(1,4) link

Blood & Carbohydrates METABOLISM

- entire set of life-sustaining chem reactions (involved in energy from food, waste NAD+  NADH: oxidation (release energy)
processing & removal, muscle growth, photosynthesis, cell division, reproduction) NADH  NAD+: reduction (need energy)
- in course of 40 yrs, while maintaining constant weight, body process 6 tons food & as NAD+ receives H- forming NADH, there’s H+ addition
10000 gallons of water
goal: convert chem potential energy in food to potential energy in form of ATP
Metabolic pathway- smaller sets of sequential reactions of organized chem reactions
- need enzymes, so organisms can control (accelerate/suppress) these acc to
needs by upregulating, downregulating, inhibiting, activating enzymes
Types
Linear- series of reactions not repeated
Circular- repeating reactions where final product is also initial reactant
Spiral- series of repeated actions used to break down/build compound

FADH2  FAD: oxidation

FAD  FADH2: reduction; FAD accepts H- from other species & H+ from solution

ACYL T.- CoA (H-CoA): derivative of Vit B pantothenic acid

CoA’s active form: -SH in coenzyme’s ethanethiol subunit

Metabolite- species produced in reactions of metabolic pathway

Types
Catabolism- breakdown; release energy & waste
Ex: carb digestion: starch  polysaccharide  maltose & dextrin  glucose
Anabolism- building; require energy
ex: protein synthesis: nucleic acid  amino acid  protein Energy Production
Sites
Anaerobic M. – no O2; in cytoplasm Aerobic M.- needs O2; in mitochondria

Coenzymes in Metabolism
Coenzyme- activate enzyme; one of substrate/reactant in catalyzed reaction
- substrates are also called coenzymes: these are common in enzymatic
reactions where they donate/accept electrons/atoms to/from other substrates

5 group-transfer coenzymes

4 General Stages of Catabolism

PHOSPHATE TRANSFER= ADP  ATP: adding phosphate group need energy
1. DIGESTION
ATP  ADP: removing “ release energy
- body breaks down carb, protein, triglyceride polymers into monomer residues
 reason why ATP is energy source since it releases energy when needed by body
- carbs are broken to poly to monosaccharides
(mouth & stomach)
a. Salivary amylase breaks starch to catalyze amylose & amylopectin hydrolysis to form
maltose (α-1,4 bond) & dextrins (small oligosaccharides w/ 3-8 glucose residues)
b. When mixture enters stomach, no digestion happens (acid denatures s. amylase)
(small intestine)
c. Pancreatic amylase: catalyze dextrin hydrolysis to form maltose & isomaltose
Maltase: “ maltose to glucose
Isomaltase: “ isomaltose to glucose
ELECTRON T.: Reduction- electron gain; hydride ion (H-) bonds in organic molecule
- - + Lactase: “ lactose to glucose & galactose
Oxidation- e loss; H or hydrogen ion (H ) is removed from organic mol
 Sucrose: “ sucrose to glucose & fructose energy for forming 4 NADH & 2 ATP
 oligo- & polys can be converted to monos for sugars to pass through intestine wall &
into bloodstream so they’re available to cells
 monos are transported into cells by passive diffusion by transmembrane protein
 not all carbs are digestible (cellulose: β-1,4 glucose-glucose bonds; salivary amylase
only catalyze α-1,4 glucose-glucose disaccharide)

A. GLYCOLYSIS
- 10 sequential reactions converting 1 glucose to 2 pyruvates & 2 H2O 2. ACETYL-COA PRODUCTION
- Goodness Gracious, Father Franklin Did Go By Picking Pumpkins to Prepare Pies - aerobic; pyruvate from cytoplasm to mitochondria & turned to acetyl-CoA & CO2
 10 reactions’ products: net gain of 2 ATP & 2 NADH a. Pyruvate is oxidized & decarboxylated (carboxylate ion removal, producing CO2)
b. Energy release by oxidation is transferred to NADH

 not all energy from glucose is transferred to ATP & NADH in glycolysis (some was lost
as heat; most of glucose’s chem potential energy remains in 2 pyruvates)

3. CITRIC ACID / KREB’S CYCLE

- final stage of carb breakdown
- in 1st reaction, acetyl-CoA reacts w/oxaloacetate (reactant)
- in Kreb’s cycle, oxaloacetate is reactant of 1st reaction & product of 2nd reaction
- Citrate is Krebs Special Substrate For Making Oxide Low Acetate (oxaloacetate)

 when 1 a-CoA is completely processed, its PE turned to PE in 3 NADH, 1 FADH2, 1 ATP

 some energy is lost as heat
 CO2 from Kreb’s cycle & stage 2 metabolism is one of end-products of food metabolism
(CO2: most oxidized form of carbon in organic compounds, so it has very low energy)
(energy in food & food metabolites w/ these carbons were extracted in catabolism)

fate of other monos:

 can be catabolized if they’re converted to intermediates in glycolysis pathway:
galactose to glucose-6-phosphate
mannose to fructose-6phosphate
fructose to fructose-6-phosphate/dihydroxyacetone phosphate
fates of Pyruvate
B. ANAEROBIC CONDITION
- during strenuous activity, O2 in muscle depletes; pyruvate from glycolysis remains in
cytoplasm & converted (reduced) to lactate (released by muscle to circulatory
system & absorbed by liver

Gluconeogenesis
- lactate is converted back to pyruvate to glucose for future use
- anabolic; non-carb species (pyruvate, lactate, glycerol, AA) are formed to glucose
- when glucose’s formed; liver releases it to bloodstream, raising blood glucose level
- maintain normal blood glucose level during inadequate carb intake
Gluconeogenesis vs Glycolysis
- difference in 3 irreversible glycolysis reactions 1, 3, & 10
- Gluconeogenesis doesn’t use R10 but uses enzymes to enable reverse of R1 & R3
- “ happens primarily in liver
Glycogenesis- turn glucose to glycogen stored in liver/muscle tissue (excess glucose)
Glycogenolysis- hydrolyze glycogen to glucose released in blood (lacking glucose)

C. AEROBIC CONDITION 4. ELECTRON TRANSPORT CHAIN & OXIDATIVE PHOSPHORYLATION

- 1 glucose produce 2 acetyl-CoA & provides
- NADH must be located within mitochondrial matrix; is transported through:
 malate-aspartate shuttle - as e- move through complex I, III, & IV, energy is released, which will be used by
- NADH is oxidized in intermembrane space by transferring e- to inner complexes to actively transport H+ from lower H+ conc (mitochondrial matrix) to a
mitochondrial membrane-bound FAD, forming FADH2 that undergo oxidative p. higher conc (intermembrane space)
glycerol 3-phosphate shuttle - energy from NADH & FADH2 (originally in food) is converted to electrochemical energy
within mitochondria (electron transport)
- electron transfer intermediates in ET are called “electron transport chain”
Chemiosmosis
- ATP synthase catalyzes reaction that produces ATP & deliver energy to make ATP
synthesis occur spontaneously (from higher to lower H+ conc)
- protons from intermembrane space returns to mitochondrial matrix through ATP
synthase which charges so ADP can turn into ATP

Regulation of Blood Glucose Concentration

Normal: 80-110 mg/dl
Hyperglycemia- kidney, neurological system, cardio system, eyes, feet, legs damage
Hypoglycemia- between meals & starvation

Triglyceride Metabolism
1. DIGESTION
- Triglycerides hydrolyzed to diglycerides, then to monoglycerides
Oxidative P - starts in mouth by lingual lipase
- e- from NADH/FADH2 are transferred through e- intermediates to O2 to provide - majority of dietary triglycerides are digested in small intestine
energy to produce ATP
 Large globules formed in mouth & stomach are emulsified by bile salts
- 2 components: electron transport chain & chemiosmosis
 Emulsification allows pancreatic lipase to catalyze partial hydrolysis of emulsified
- due to H+ available in solution (from H2O or acid form of other species), when e- are
tri- & diglycerides to produce fatty acids & monoglycerides
transferred to O2, reaction occurs:
- fatty acids & monoglycerides from intestine absorb into intestine walls, then re-
 O2 is reduced (gains e-); final acceptor of e- in food catabolism assembled back into triglycerides
- since lymph, blood, & intercellular fluids are aqueous & triglycerides hydrophobic, latter
Protein Complex
must be emulsified to be transported to body by chylomicrons (small lipoprotein
- inner mitochondrial membrane composed of a core w/emulsified triglyceride, cholesterol,
+
- use energy from electron transfer to move H from lower conc (mitochondrial matrix) hydrophobic vitamins surrounded by lipid monolayer
+
to higher H conc (intermembrane space)
- Adipose cells are major repository for triglycerides

2. ACETLY-COA PRODUCTION
- when body is fasting/exercise, lipids mobilizes energy production by lipolysis
(triglyceride hydrolysis to fatty acids & glycerol)
activation reaction- enable acyl group from fatty acids to pass through inner
mitochondrial membrane & enter matrix, where subsequent fatty
Total ATP produced in 1 Glucose acid catabolism occur

β-Oxidation of Fatty Acids- not cyclic, last product isn’t used as reactant of 1st reaction

# of ATP produced from NADH/FADH2 depends on cell & its current conditions
1 NADH produce 3 ATP; 1 FADH2 produce 2 ATP
Summary of NADH Oxidation & FADH2 on Oxidative Phosphorylation Summary of Fatty Acid Catabolism
- when NADH & FADH2 are oxidized, their e- are transferred, through intermediates, to#O2
- if “N” is carbons contained in fatty acyl-CoA, it undergo [(N/2) -1] β- oxidation cycles
 (ex for 8- carbon FA, there are 3 cycles) Monounsaturated- 1 carbon–carbon double bond
Total ATP production of 8-Carbon FA = 113 Polyunsaturated- 2 or more carbon–carbon double bonds
Ketogenesis- many triglycerides are catabolized producing many Acetyl-CoA that enters Omega-3- unsaturated; end double bond 3 C atoms away from methyl end
Citric Acid Cycle; acetyl-CoA reacts w/ other acetyl-CoA to produce ketone bodies Omega-6- “ “ “ “ “ 6 carbon atoms away from methyl end
- heart muscles & renal cortex use ketone bodies more readily than glucose
- starvation: brain gets 75% of its energy from ketone bodies; cells can’t get glucose
extremely high rates of fatty acid catabolism results in dangerous levels of
ketone bodies due to production of higher H3O+
blood becomes acidic (acidosis), cause tissue dysfunction & CNS damage
Ketoacidosis- acidosis is caused by excess ketone bodies

Unsaturated FA & Double Bond Position

- numerical based shorthand system specifies key structural parameters for. 2 numbers
separated by colon are used to specify # carbon atoms & # carbon-carbon double bonds
present. (ex. 18:0 - no double bond, 18:2 - 2 double bonds)
Triglyceride Anabolism - to specify double bond positioning within carbon chain, preceding notation is added
- FA are produced by spiral metabolic pathway opposite direction as β-oxidation: builds- w/delta ( Δ) followed by 1 or more superscript numbers. (ex. 18:3 (Δ⁹,¹²)
up fatty acyl-CoA by repeating reactions that add acetyl-CoA to fatty acyl-CoA structure - Double bond positioning denoted by omega (ω)
- body synthesize almost all FA it except linoleic & linolenic acid (only obtained through (ω-6) for omega 6 (ω-3) for omega 3
dietary triglycerides, so classified as essential FA)
Non-Essential FA- synthesized in body Essential- from diet (Linoleic & Linolenic)
Protein Metabolism
Common Saturated FA
1. DIGESTION
- when dietary proteins are digested, they turn to AA, then used in metabolic pathways
- proteins are converted to AA by hydrolysis of peptide bonds
- AA can’t be stored, so excess are catabolized for energy production in liver through:
Transamination, Oxidative Deamination, Urea Cycle
(glucose store as glycogen=glycogenesis; excess FA stored as trigl=triglyceride synthesis)
- starts in stomach, continues in intestine
stomach: acidic env & proteolytic pepsin catalyze protein hydrolysis to AA & oligopeptide
small intestine: unhydrolyzed oligopeptides broken down to AA by peptidases (Trypsin, Unsaturated FA
Chymotrypsin, Carboxypeptidase, Aminopeptidase)
transformation of AA to Intermediate Metabolites:
Transamination- transfer of quaternary ammonium group (NH3+) bound to AA α-carbon
is transferred to α- keto acid
Oxidative Deamination- removal of NH3+
TRIACYLGLYCEROLS
Entry of metabolites in Kreb’s Cycle - energy storage, insulator, shock absorber
- transformed intermediate metabolites turned to glucose, ketone bodies, or - concentrated in special cells (adipocytes) nearly filled w/material.
undergo citric acid cycle. - adipose tissue under skin, abdominal cavity, mammary glands, around organs
Urea Cycle - fat content of normal humans survive starvation for 2-3 months
- free ammonium ions (NH4+) produced in oxidative deamination are toxic at elevated - FA are carboxylic acids involved in triacylglycerol formation.
- humans & terrestrial vertebrates can convert NH4+ to urea Simple- triester formed from esterification of glycerol w/ 3 identical FA
Mixed- “ “ “ w/more than 1 kind of FA

LIPIDS
- insoluble/ sparingly soluble in water; soluble in nonpolar organic solvents.
- 18-25% of body mass in lean adults; fats, oils, waxes
- formed from long chain hydrocarbons; may contain O, P, N, S
Function
- bilayer in biological membranes.
a. structural components as protective barrier Esterification- 1 glycerol reacts w/3 FA; each of 3 hydroxyl groups is esterified.
b. protective functions in bacteria, plants, insects, vertebrates as part of
outer coating between body & env
- lipids w/ hydrocarbon side chains serve as energy stores
- transport system; cell membranes have transport proteins (semipermeable)
- intra- & intercellular signaling events
Classification acc to Chemical Structure
1. Open-chain-polar head groups & nonpolar tails
 Fatty Acids, Triglycerides, Sphingolipids, Phosphoacylglycerol, Glycolipids
2. Fused-ring/Steroid (Cholesterol)
- triacylglycerol mixture; solid/semi-liquid at room temp (25o C); animals
Types of Fatty Acids (Fatty Acid- naturally-occurring monocarboxylic acid)
- saturated FA predominate, some unsaturated FA can be present
Saturated- carbon chain w/all carbon–carbon bonds are single bonds.
- triacylglycerol mixture; liquid at room temp (25o C); plants
 - mono- & polyunsaturated FA than fats - 1 FA & 1 phosphate attached to 1 sphingosine & 1 alcohol attached to phosphate
- sphingomyelins (alcohol esterified to phosphate group choline)
Chemical Reaction of Triacylglycerol
structure: FA attached to sphingosine-NH2 group via amide linkage
HYDROLYSIS phosphate attached to sphingosine terminal-OH group via ester linkage,
- reverse esterification; requires presence of acid/base (reactant: WATER) additional alcohol esterified to phosphate group
- triglyceride  glycerol + 3 FA
Complete- all 3 FA are removed Partial- 1 or more FA remain attached to glycerol

2. SPHINOGLYCOLIPIDS- 2nd of 3 major types of membrane lipids.

- contains fatty acid & carbohydrate component attached to sphingosine
- cerebrosides occur in brain (7% of dry mass) & myelin sheath
3. CHOLESTEROL- 3rd of 3 major types of membrane lipids.
SAPONIFICATION
- structure differs markedly from other membrane lipids:
- carried out in alkaline solution; triglyceride  glycerol + FA salts (reactant: BASE)
a. no fatty acid residues present
Saponifiable- esters of FA, polyos, glycerol (w/FATTY ACID)
b. glycerol & sphingosine aren’t present as platform molecule
- easily hydrolyzed by sodium hydroxide; w/ester linkages
Nonsaponifiable- fat-soluble vit A & B; no ester bonds, has cholesterol (STEROID FORM) Cell Membrane
- can’t be hydrolyzed by sodium hydroxide
- lipid-based structure separating cell’s aqueous-based interior from aqueous env
lipid bilayer- 2-layer-thick structure of phospholipids & glycolipids
- nonpolar tails in middle, polar heads on outside surfaces
Passive Transport- diffusion from higher to lower conc
Facilitated- use membrane proteins from higher to lower conc
Active- against conc gradient using cellular energy

HYDROGENATION Emulsification Lipids: BILE ACIDS

- H addition across carbon - carbon multiple bonds, increasing degree of saturation as - large lipid globules broken down into small lipid globules
some double bonds are converted to single bonds Cholesterol vs Bile
- unsaturated  saturated - tri- / dihydroxy cholesterol derivatives.
- carbon 17 side chain of cholesterol has been oxidized to carboxylic acid.
- oxidized acid side chain is bonded to AA (glycine/taurine) through amide linkage

Messenger Lipids
STEROID HORMONES
a. Sex hormones- reproduction & secondary sex characteristics
Estrogen, Androgen, Progestin (pregnancy)
b. Adrenocorticoid h: mineralocorticoid (Na & K balance in body fluids & cells)
OXIDATION glucocorticoids (glucose metabolism & counteract inflammation)
- breaks C-C double bonds present in FA of triacylglycerol; oxidizing agent: O2 (from air)
- FA  smaller carbons (aldehyde & carboxylic acid)

Membrane Lipids
1. PHOSPHOLIPIDS- 1 or more FA, 1 phosphate, platform molecule, alcohol
Glycerophospholipids- glycerol-based
- 3 AA: phosphatidylcho line (lecithin), phosphatidylethanolamine,
phosphatidylserine
- polar head group is water-soluble; nonpolar tail chains are water-insoluble but
nonpolar substance-soluble
Sphingophospholipids- sphingosine-based; structure based on 18-carbon EICOSANOID
monounsaturated aminodialcohol sphingosine Prostaglandin- has cyclopentane ring & O2 functional group
b. Thromboxane- cyclic ether ring & O2 functional group
c. Leukotriene- 3 conjugated double bonds & hydroxyl groups

Protective Coating Lipids: BIOLOGICAL WAX

- FA are saturated & has 14-36 carbon atoms
- alcohol may be saturated/unsaturated & has 16- 30 carbon atoms
- w/ small, weakly polar “head” & 2 long nonpolar “tails”. Head’s polarity is not sufficient
to impart any degree of water solubility to molecule