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 REVIEW
of
CARBOHYDRATES
 CARBOHYDRATES
 Hydrates of carbon [Cn(H2O)m]

 Polyhydroxyaldehyde or polyhydroxyketone, or
substance that gives these compounds on hydrolysis

 Most abundant organic compound in the plant world

 Chemically made up of skeletal C,H which is usually

2x the number of C, highly variable number of O,
occasional N & S

 Linked to many lipids and proteins

 FUNCTIONS of
CARBOHYDRATES
 Storehouses of chemical energy
 Glucose,starch, glycogen
 Structural components for support
 Cellulose, chitin, GAGs
 Essential components of nucleic acids
 D-ribose, 2-deoxy-D-ribose
 Antigenic determinants
 Fucose, D-galactose, D-glucose, N-acetyl-D-
glucosamine, D-acetyl-D-galactosamine
 SPECIFIC CARBOHYDRATES
Monosaccharides
 Glucose (dextrose, grape sugar, blood sugar)
 Can be stored as glycogen
 Most metabolically important monosaccharide

 Fructose (levulose)

 Galactose (brain sugar)

 Mannose
 Targets lysosomal enzymes to their destinations
 Directs certain proteins from Golgi body to lysosomes
 Disaccharides
 Sucrose (table sugar, cane sugar,
saccharose)
glucose & fructose linked αβ1-2
 Lactose (milk sugar) glu & gal linked β 1-4
 Maltose (malt sugar) 2 glucose linked
α 1-4
 Trehalose (mycose) 2 glucose linked
α 1-1
 Gentiobiose (amygdalose) 2 glucose
linked β 1-6
 Cellobiose 2 glucose linked β 1-4
CLASSES OF CARBOHYDRATES
Number of C
 Triose, tetroses, pentose, hexose, heptulose
Number of saccharide units
 Monosaccharides, disaccharides, oligosaccharides (2 to 10
units), polysaccharides
Position of carbonyl (C=O) group
 Aldose if terminally located
 Ketose if centrally located
Reducing property
 Reducing sugars (all monosaccharides)
 Nonreducing sugars (sucrose)
 STRUCTURAL PROJECTIONS OF
MONOSACCHARIDES
 FISCHER by Emil Fischer
(Nobel Prize in Chemistry 1902)

 2-D representation for showing

the configuration of a stereocenter

 Horizontal lines project forward

while vertical lines project towards
the rear

 D (R or +) or L (S or -)
 HAWORTH by Walter Haworth
(Nobel Prize in Chemistry 1937)

 A way to view furanose (5-membered ring) and

pyranose (6-membered ring) forms of
monosaccharides

 The ring is drawn flat and viewed through its edge

with the anomeric carbon on the the right and the
oxygen atom on the rear
ANOMERIC CARBON
 CHAIR & BOAT
CONFORMATIONS
AMINO SUGARS
 REDUCING PROPERTY
Ketose O H

H OH- C
H – C – OH
H C OH
C=O Enediol O O-

R HO H OH- R
C
C
Aldose Oxidizing
H C OH
C agent R
R OH
Aldonate
 ABO ANTIGENS
N-acetyl- D-galactose N-acetyl-
TYPE A
D-galactosamine D-glucosamine
Fucose

D-galactose D-galactose N-acetyl-

TYPE B
D-glucosamine
Fucose

D-galactose N-acetyl-
TYPE O
D-glucosamine
Fucose
 POLYSACCHARIDES
 STARCH
 Storage carbohydrate in plants

 Two principal parts are amylose (20-25%) &

amylopectin (75-80%) which are completely
hydrolyzed to D-glucose

 Amylose is composed of continuous, unbranched

chain of 4000 D-glucose linked via α 1-4 bonds

 Amylopectin is a chain of 10,000 D-glucose units linked

via α 1-4 bonds but branching of 24-30 glucose units is
started via α 1-6 bonds
 GLYCOGEN

 Energy-reserve carbohydrate in animals

 Highlybranched containing approximately

106 glucose units linked via α 1-4 bonds & α
1-6 bonds

 Well-nourished adult stores 350 g. of it

equally divided between the liver and
muscles
 CELLULOSE
 Plant skeletal polysaccharide

 Linear chain of 2200 glucose units linked

via β 1-4 bonds

 High mechanical strength is due to

aligning of stiff fibers where hydroxyl form
hydrogen bonding
 ACIDIC POLYSACCHARIDES
 Also called mucopolysaccharides (MPS) or
glycosaminoglycans (GAG)

 Polymers which contain carboxyl groups and/or

sulfuric ester groups

 Structural and functional importance in connective

tissues

 Interact with collagen to form loose or tight networks

 ACIDIC POLYSACCHARIDES
 HYALURONIC ACID
 Simplest GAG
 Contains 300-100,000 repeating units of D-glucuronic
acid and N-acetyl-D-glucosamine
 Abundant in embryonic tissues, synovial fluid, and the
vitreous humor to hold retina in place
 Joint lubricant & shock absorber

 HEPARIN
 Heterogeneous mixture of variably sulfonated chains
 Stored in mast cells of the liver, lungs and the gut
 Naturally-occurring anticoagulant by acting as
antithrombin III and antithromboplastin
 Composed of two disaccharide repeating units A & B;
 A is L-iduronic acid-2-sulfate linked to 2-deoxy-2-sulfamido-D-
galactose-6-sulfate
 B is D-glucuronic acid beta-linked to 2-deoxy-2-sulfamido-D-glucose-
6-sulfate
HEPARAN SULFATE

CHONDROITIN SULFATE
 Most abundant in mammalian tissues
 Found in skeletal and soft connective tissues
 Composed of repeating units of N-acetyl galactosamine sulfate linked
beta1-4 to glucuronic acid

KERATAN SULFATE

DERMATAN SULFATE
 Found in skin, blood vessels, heart valves, tendons, aorta, spleen
and brain
 The disaccharide repeating units are L-iduronic acid and N-
acetylgalactosamine-4-sulfate with small amounts of D-glucuronic acid
 GLYCOLYSIS
 The specific pathway by which the body
gets energy from monosaccharides
First stage is ACTIVATION
 At the expense of 2ATPs glucose is
phosphorylated
Step #1
formation of glucose-6-phosphate
Step # 2
isomerization to fructose-6-phosphate
Step # 3
Second phosphate group is attached to yield fructose-
1,6-bisphosphate

Second stage is C6 to 2 molecules of C3

Step # 4
Fructose-1,6-bisphosphate is broken down into two C3
fragments
glyceraldehyde-3-phosphate (G-3-P) and

dihydroxyacetone phosphate (DHAP)

Only G-3-P is oxidized in glycolysis. DHAP is converted

to G-3-P as the latter diminishes.
 ATP-YIELDING Third stage
Step # 5
Glyceraldehyde-3-phosphate is oxidized to 1,3-
bisphosphoglycerate; hydrogen of aldehyde is
removed by NAD+
Step # 6
Phosphate from the carboxyl group is transferred
to the ADP yielding ATP and 3-
phosphoglycerate
Step # 7
Isomerization of 3-phosphoglycerate to 2-
phosphoglycerate
Step # 8
Dehydration of 2-phosphoglycerate to
phosphoenolpyruvate (PEP)

Step # 9
Removal of the remaining phosphate to yield
ATP and pyruvate

Step # 10
Reductive decarboxylation of pyruvate to
produce ethanol and CO2
 REACTIONS OF GLYCOLYSIS
STEP REACTION ENZYME REACTION ΔG in
TYPE kJ/mol

1 Glucose + ATP  Hexokinase Phosphoryl -33.5

transfer
G-6-P + ADP + H+

2 G-6-P  F-6-P Phosphoglucose Isomerization -2.5

isomerase

3 F-6-P + ATP  Phosphofructo- Phosphoryl -22.2

kinase transfer
F-1,6-BP + ADP + H+
STEP REACTION ENZYME REACTION TYPE ΔG in
kJ/
mol
4 F-1,6-BP  DHAP + GAP Aldolase Aldol cleavage -1.3

5 DHAP  GAP Triose Isomerization +2.5

phosphate
isomerase
6 GAP + Pi + NAD+  Glyceraldehyde Phosphorylation +2.5
1,3-BPG + NADH + H+ -3-Phosphate coupled to
Dehydrogenase oxidation
7 1,3-BPG + ADP  Phosphoglycer- Phosphoryl +1.3
3-phosphoglycerate +ATP ate kinase transfer

8 3-phosphoglycerate  Phosphoglyce- Phosphoryl shift +0.8

2-phosphoglycerate rate mutase

9 2-phosphoglycerate  Enolase Dehydration -3.3

PEP + HOH

10 PEP + ADP + H+  pyruvate + ATP Pyruvate kinase Phosphoryl -16.7

transfer
 CITRIC ACID CYCLE
STEP REACTION ENZYME PROSTHET REACTION ΔGo
IC GROUP TYPE in
kJ/
mol
1 acetylCoA + oxaloacetate + HOH Citrate Condensation -31.4
 citrate + CoA + H+ synthase

2a Citrate  cis-aconitate + HOH Aconitase Fe-S Dehydration +8.4

2b Cis-Aconitate + HOH  Aconitase Fe-S Hydration -2.1

isocitrate
 CITRIC ACID CYCLE
STEP REACTION ENZYME PROSTHET REACTION ΔGo
IC GROUP TYPE in
kJ/
mol
3 Isocitrate + NAD+  Isocitrate Decarboxylati - 8.4
α-ketoglutarate + CO2 + Dehydro- on & oxidation
NADH genase

4 α-ketoglutarate + NAD+ CoA  α- Lipoic Decarboxyla- -30.1

succinyl CoA + CO2 + ketogluta- acid, FAD, tion &
NADH rate TPP oxidation
dehydro-
genase
complex
5 Succinyl CoA + Pi + GDP  Succinyl Substrate- -3.3
succinate + GTP + CoA CoA level
synthet- phosphoryla-
ase tion
 CITRIC ACID CYCLE
STEP REACTION ENZYME PROSTHET REACTION ΔGo in
IC GROUP TYPE kJ/
mol
6 Succinate + FAD (enzyme-bound) Succinate FAD, Fe-S Oxidation 0
 fumarate + FADH2 dehydro-
(enzyme-bound) genase

7 Fumarate + HOH  L-malate Fumarase Hydration -3.8

8 L-malate + NAD+  Malate Oxidation +29.7

oxaloacetate + NADH + H+ dehydro-
genase
REGULATION OF TCA CYCLE
Pyruvate
- ATP, acetyl CoA & NADH

Acetyl CoA

Oxaloacetate Citrate

Malate
Isocitrate

Fumarate - ATP & NADH ICD

+ ADP
Α-Ketoglutarate
Succinate
Α-KGD
Succinyl
- ATP, succinyl
CoA CoA & NADH
 BIOSYNTHETIC ROLES
OF TCA CYCLE
Pyruvate
Other amino
acids,
purines & Acetyl CoA
pyrimidines
Oxaloacetate Citrate Fatty acids,
sterols
Aspartate Malate
Isocitrate

Fumarate
Other
amino
Α-Ketoglutarate acids &
Succinate purines
Porphyrins, Glutamate
heme, Succinyl
chlorophyll CoA
 NOTES TO REMEMBER
 The unusual thing about the structure of N-
acetylmuramic acid compared to other
carbohydrates is the presence of a lactic acid
side chain.

 Cell walls of plants are cellulosic (polymer of

D-glucose); bacterial cell walls consist mainly
of polysaccharide crosslinked to peptide
through murein bridges; and fungal cell walls
are chitinous (polymer of N-acetyl-β-D-
glucosamine)
 Glycogen and starch differ mainly in the degree
of chain branching.

 Enantiomers are nonsuperimposable, mirror-

image stereoisomers differing configuration
on all carbons while diastereomers are
nonsuperimposable nonmirror-image
stereoisomers differing only on two
carbons.

 Fischer projection of glucose has 4 chiral

centers while its Haworth projection has 5
chiral centers.
 Sugar phosphate is an ester bond
formed between a sugar hydroxyl and
phosphoric acid.

 A glycosidic bond is an acetal which can

be hydrolyzed to regenerate the two
original sugar hydroxyls.

 A reducing sugar is one that has a free

aldehyde group that can be easily
oxidized.
 Major biochemical roles of glycoproteins
are signal transduction as hormones,
recognition sites for external molecules in
eukaryotic cell membranes, and defense as
immunoglobulins.

 L-sorbitol is made by reducing D-glucose.

 Arabinose is a ribose epimer, thus, its

derivatives ara-A and ara-C if substituted
for ribose act as inhibitors in reactions of
ribonucleosides.
 Two best precursors for glycogen are
glucose and fructose.

 Cellulose because of the β- bonding is linear

as to structure and structural as to role while
starch because of α-bonding coils with
energy storage role.

 The highly branched nature of glycogen

gives rise to a number of available glucose
molecules at a time upon hydrolysis to
provide energy. A linear one provides one
glucose at a time.
 The enzyme β-amylase is an exoglycosidase
degrading polysaccharides from the ends. The
enzyme α-amylase is an endoglycosidase
cleaving internal glycosidic bonds.

 Dietary fibers bind toxic substances in the gut

and decreases the transit time, so harmful
compounds such as carcinogens are removed from
the body more quickly than would be the case with
low-fiber diet.

 The sugar portions of the blood group

glycoproteins are the source of the antigenic
difference.
 Cross-linking can be expected to play a role in the
structures of cellulose and chitin where mechanical
strength is afforded by extensive hydrogen bonding.

 Converting a sugar to an epimer requires inversion

of configuration at a chiral center. This can only be
done by breaking and reforming covalent bonds.

 Vitamin C is a lactone (a cyclic ester) with a double

bond between two of the ring carbons. The
presence of a double bond makes it susceptible to
air oxidation.

 The sequence of monomers in a polysaccharide is

not genetically coded and in this sense does not
contain any information unlike the nucleotide
sequence.
 Glycosidic bonds can be formed between the side
chain hydroxyls of serine or threonine residues
and the sugar hydroxyls. In addition, there is a
possibility of ester bonds forming between the side
chain carboxyl groups of aspartate or glutamate
and the sugar hydroxyls.

 In glycolysis, reactions that require ATP are:

1. phosphorylation of glucose (HK,GK)
2. phosphorylation of fructose-6-phosphate (PFK)
Reactions that produce ATP are:
1. transfer of phosphate from 1,3-
bisphosphoglycerate to ADP (PGK)
2. transfer of phosphate from PEP to ADP (PK)
 In glycolysis, reactions that require NADH are:
1. reduction of pyruvate to lactate (LDH)
2. reduction of acetaldehyde to ethanol
(alcohol dehydrogenase)
Reactions that require NAD are:
1. oxidation of G-3-P to give 1,3-DPG (G-3-PD)

 NADH-linked dehydrogenases are LDH, ADH & G-

3-PD.

 The purpose of the step that produces lactate is to

reduce pyruvate so that NADH can be oxidized to
NAD+ needed for the step catalyzed by
glyceraldehyde-3-phosphate.
 Aldolase catalyzes the reverse aldol condensation
of fructose-1,6-bisphosphate to glyceraldehyde-3-
phosphate and DHAP.

 The energy released by all the reactions of

glycolysis is 184.5 kJ mol glucose/mol. The energy
released by glycolysis drives the phosphorylation of
two ADP to ATP for each molecule of glucose,
trapping 61.0 kJ mol/glucose. The estimate of 33%
efficiency comes from the calculation (61.0/184.5) x
100 = 33%.

 There is a net gain of two ATP molecules per

glucose molecule consumed in glycolysis. The
gross yield of 4 ATPs per glucose molecule, but the
reactions of glycolysis require two ATP per glucose.
 Pyruvate can be converted to lactate, ethanol or
acetylCoA.

 The free energy of hydrolysis of a substrate is the

energetic driving force in substrate-level
phosphorylation. An example is the conversion of
glyceraldehyde-3-phosphate to 1,3-
bisphosphoglycerate.

 Coupled reactions in glycolysis are those reactions

catalyzed by hexokinase, phosphofructokinase,
glyceraldehyde-3-phosphate dehydrogenase,
phosphoglycerokinase, and pyruvate kinase.
 Isozymes allow for subtle control of the enzyme to
respond to different cellular needs. For example, in the
liver, LDH is most often used to convert lactate to
pyruvate, but the reaction is often reversed in the
muscles. Having a different isozyme in the liver and
the muscle allows for those reactions to be
optimized.

 Fructose-1,6-bisphosphate can only undergo the

reactions of glycolysis. The components of the
pathway up to this point can have other metabolic
fates.

 The physiologically irreversible glycolytic steps

are those catalyzed by HK, PFK and PK. Thus, they
are controlling points in glycolysis.
 Hexokinase is inhibited by glucose-6-phosphate.
Phosphofructokinase is inhibited by ATP and citrate.
Pyruvate kinase is inhibited is inhibited by ATP,
acetylCoA and alanine.

 Phosphofructokinase is stimulated by AMP and

fructose-2,6-bisphosphate.
Pyruvate kinase is stimulated by AMP and fructose-
1,6-bisphosphate.

 An isomerase is a general term for an enzyme that

changes the form of a substrate without changing
its empirical formula.

 A mutase is an enzyme that moves a functional

group such as a phosphate to a new location in a
substrate molecule.
 The glucokinase has a higher Km for glucose than
hexokinase. Thus, under conditions of low glucose,
the liver will not convert glucose to glucose-6-
phosphate, using a substrate that is needed
elsewhere. When the glucose concentration becomes
higher, however, glucokinase will function to help
phosphorylate glucose so that it can be stored as
glycogen.

 The net yield of ATP from glycolysis is the same, 2

ATP, when either fructose, mannose, and
galactose is used. The energetics of the conversion
of hexoses to pyruvate are the same regardless of
hexose type.

 The net yield of ATP is 3 from glucose derived from

glycogen because the starting material is glucose-1-
phosphate. One of the priming reactions is no longer
used.
 A reaction with a negative ΔGo is
thermodynamically possible under standard
conditions.

 Individuals who lack the gene that directs the

synthesis of the M form of the enzyme PFK can
carry on glycolysis in their livers but suffer muscle
weakness because they lack the enzyme in muscle.

 The reaction of 2-PG to PEP is a dehydration (loss of

water) rather than a redox reaction.

 The hexokinase molecule changes shape

drastically on binding to substrate, consistent with
the induced fit theory of an enzyme adapting itself to
its substrate.
 ATP is an inhibitor of several steps of glycolysis as
well as other catabolic pathways. The purpose of
catabolic pathways is to produce energy, and high
levels of ATP mean the cell already has sufficient
energy. G-6-P inhibits HK and is an example of
product inhibition. If G-6-P level is high, it may
indicate that sufficient glucose is available from
glycogen breakdown or that the subsequent enzymatic
steps of glycolysis are going slowly. Either way there
is no reason to produce more G-6-P.

 Phosphofructokinase is inhibited by a special

effector molecule, fructose-2,6-bisphosphate,
whose levels are controlled by hormones. It is also
inhibited by citrate, which indicates that there is
sufficient energy from the TCA cycle probably from fat
or amino acid catabolism.
 PK is also inhibited by acetylCoA, the presence of
which indicates that fatty acids are being used to
generate energy for the citric acid cycle.

 The main function of glycolysis is to feed carbon

units to the TCA cycle. When these carbon
skeletons can come from other sources, glycolysis is
inhibited to spare glucose for other purposes.

 Thiamine pyrophosphate (TPP) is a coenzyme in the

transfer of 2-carbon units. It is required for catalysis by
pyruvate decarboxylase in alcoholic fermentation. The
important part of TPP is the five-membered ring where
a C is found between an S and N. This carbon forms a
carbanion and is extremely reactive, making it able to
perform nucleophilic attack on carbonyl groups
leading to decarboxylation of several compounds in
different pathways.
 TPP is a coenzyme required in the reaction
catalyzed by pyruvate carboxylase. Because this
reaction is a part of the metabolism of ethanol, less
will be available to serve as a coenzyme in the
reactions of other enzymes that require it.

 Animals that have been run to death have

accumulated large amounts of lactic acid in their
muscle tissue, accounting for the sour taste of their
meat.

 Conversion of glucose to lactate rather than pyruvate

recycles NADH.

 The formation of fructose-1,6-bisphosphate is the

committed step in glycolysis. It is also one of the
energy-requiring steps of the said pathway.
 A positive ΔGo does not necessarily mean
that the reaction has a positive ΔG.
Substrate concentrations can make a
negative ΔG out of a positive ΔGo.

 The entire pathway can be looked at as a

large coupled reaction. Thus, if the overall
pathway has a negative ΔG, an individual step
may be able to have a positive ΔG and the
pathway can still continue.
 In glycogen storage, the reactions that require ATP are:
1. formation of UDP-glucose from glucose-1-phosphate
and UTP (indirect requirement since ATP is needed
to regenerate UTP) (UDP-glucose phosphorylase)
2. regeneration of UTP (nucleoside phosphate kinase)
3. carboxylation of pyruvate to oxaloacetate (pyruvate
carboxylase)
Reactions that produce ATP are NONE.

 Three differences between NADPH and NADH

1. phosphate at 2’ position of ribose in NADPH
2. NADH is produced in oxidative reactions that yield ATP
while NADPH is a reducing agent in biosynthesis.
3. Different enzymes use NADH as a coenzyme compared
to those that require NADPH.
 In glycogen storage, there is no reaction
that requires acetylCoA but biotin is
required in the carboxylation of pyruvate
to oxaloacetate.

 The four fates of glucose-6-phosphate are:

 Converted to glucose (gluconeogenesis)
 Converted to glycogen (glycogenesis)
 Converted to pentose phosphates
 Hydrolyzed to pyruvate (glycolysis)
 In making equal amounts of NADPH and pentose
phosphates, it only involves oxidative reactions. In making
mostly or purely NADPH, the use of oxidative reactions,
transketolase and transaldolase reactions, and
gluconeogenesis are required. In making mostly or only
pentose phosphates, needed reactions are transketolase,
transaldolase, and glycolysis in reverse.

 Transketolase catalyzes the transfer of 2-carbon unit, whereas

transaldolase catalyzes the transfer of a 3-carbon unit.

 It is essential that the mechanisms that activate glycogen

synthesis also deactivate glycogen phosphorylase because
they both occur in the same cell compartment. If both are on at
the same time, a futile ATP hydrolysis results. On/off
mechanism is highly efficient in its control.
 UDPG, in glycogen biosynthesis, transfers glucose to
the growing glycogen molecule.

 Glycogen synthase is subject to covalent

modification and to allosteric control. The enzyme is
active in its phosphorylated form and inactive when
dephosphorylated.

 AMP is an allosteric inhibitor of glycogen synthase,

whereas ATP and glucose-6-phosphate are
allosteric activators.

 In gluconeogenesis, biotin is the molecule to which

carbon dioxide is attached to the process of being
transferred to pyruvate. The reaction produces
oxaloacetate, which then undergoes further reactions
of gluconeogenesis. Biotin is not used in
glycogenesis and PPP.
 In gluconeogenesis, glucose-6-phosphate is
dephosphorylated to glucose (last step); in glycolysis,
G-6-P isomerizes to fructose-6-phosphate (early step).

 The Cori cycle is a pathway in which there is cycling of

glucose due to glycolysis in muscle and
gluconeogenesis in liver. The blood transports lactate
from muscle to liver and glucose from liver to muscle.

 There is a net gain of 3, rather than 2, ATP when

glycogen, not glucose, is the starting material of
glycolysis.
 Control mechanisms are important in metabolism.
They are:
 Allosteric control (takes place in msec)
 Covalent control (takes place from s to min)
 Genetic control ( longer time scale)

 Enzymes, like all catalysts, speed up the forward and

reverse reaction to the same extent. Having different
catalysts is the only way to ensure independent
control over the rates of the forward and the reverse
process.

 The glycogen synthase is an exergonic reaction

overall because it is coupled to phosphate ester
hydrolysis.
 Increasing the level of ATP is favorable to both
gluconeogenesis and glycogen synthesis.

 Decreasing the level of fructose-1,6-bisphosphate

would tend to stimulate glycolysis, rather than
gluconeogenesis and glycogen synthesis.

 If a cell needs NADPH, all the reactions of the PPP

take place. If a cell needs ribose-5-phosphate, the
oxidative portion of the pathway can be bypassed and
only the nonoxidative reshuffling reactions take place.
The PPP does not have a significant effect on the ATP
supply of a cell.

 Glucose-6-phosphate is expectedly oxidized to a

lactone rather than an open-chain ester because the
latter is easy to hydrolyze.
 In the PPP resshuffling reactions, without an
isomerase, all the sugars involved are keto
sugars that are not substrates for
transaldolase.

 Sugar nucleotides (UDPG) have two

phosphates which when hydrolyzed drives
towards the polymerization of glycogen. Thus,
they are fit for glycogenesis.
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