Course Notes 1: "Introduction to Biochemistry"

I. The science of biochemistry.

The ultimate goal of biochemistry is to explain all life processes in molecular detail.
Because life processes are performed by organic molecules the discipline of biochemistry relies
heavily on fundamental principles of organic chemistry and other basic sciences. It is of no surprise
that the first "biochemists" actually were organic chemists who specialized in the chemistry of
compounds derived from living organisms. The text provides an historical overview of some of
the key contributions of the early chemists, and of modern 20th century biochemists who have led
the discipline to where it is today. Research endeavors such as the human genome project
ultimately owe their success to basic discoveries about the structure of the DNA "double helix" by
Watson & Crick and the development of DNA sequencing methods by Fredrick Sanger.

II. The chemical basis of life.

The biomolecules such as proteins that are present in living organisms are carbon-based
compounds. Carbon is the third most abundant element in living organisms (relative abundance H
> O > C > N > P > S). The most common ions are Ca+2, K+, Na+, Mg+2, and Cl-. The properties of
biomolecules, such as shape and chemical reactivity, are best described by the discipline of organic
chemistry.

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A. Representations of molecular structures.

Your text will use skeletal, ball & stick, and space-filling models to show molecular
structures. Therefore, you must be familiar with each of these types of representations. Skeletal
and ball & stick models are good for showing the positions of nuclei in organic compounds. Space-
filling models show van der Waals radii of the atoms in molecules, i.e., the surfaces of closest
possible approach by neighboring molecules.

B. Chemical bonding.

If necessary, please review the supplemental notes at the end of this section concerning the
atomic and molecular (bonding) orbitals of carbon, nitrogen, and oxygen. sp3 and sp2 molecular
orbitals are the most prevalent in biomolecules. The orientations of bonding orbitals in space
ultimately determine the shapes of biomolecules.
 C. Functional groups.

The chemical reactions of biomolecules are dictated by the functional groups they contain.
Figure below shows the general formulas of common organic compounds and functional groups
that will be encountered constantly in the proteins, carbohydrates, nucleic acids and simple
metabolites you will study. You should be familiar with the structure, charge properties, polarity,
and basic chemical reactivity of all of these compounds and functional groups.

III. Many biomolecules are polymers.

The principle biomolecules in cells (proteins, polysaccharides, and nucleic acids) are
polymer chains of amino acids, monosaccharides, and nucleotides, respectively. Biopolymers are
formed by condensation reactions in which water is removed from the reacting monomer units.
Each monomer unit of a biopolymer is referred to as a residue.

A. Proteins.

Most of the chemical reactions of the cell are carried out by proteins. Proteins also are the
major structural components of most cells and tissues. Proteins are often called polypeptides in
reference to the fact that they are composed of amino acids held together by peptide bonds Peptide
bonds actually are amide bonds which are formed by the condensation of the carboxyl groups and
amino groups of consecutive amino acids in the polymer chain. The so- called peptide backbone
of a protein is a monotonous, regularly repeating structure. Projecting out from the backbone are
the R-groups which are the side-chains of the amino acids. In a later chapter, we will discuss how
the R-groups play a significant role in determining the 3D structure of a protein, i.e., its active
conformation.
The enzymes comprise one subclass of proteins. These proteins carry out chemical
reactions with extraordinary specificity and speed (up to 1017-fold enhancement in reaction rate).
Specificity is achieved because the binding site for reactants--the active site--is highly
complementary in shape to the reactants and products. This enzyme binds to and cleaves the
polysaccharide portion of the bacterial cell wall. Cleavage leads to osmotic lysis of the affected
bacterium. Lysozyme is present in tears and egg whites where it helps protect against unwanted
bacterial growth and infection. We will discuss the structure and function of many medically and
otherwise relevant proteins and enzymes such as myoglobin, hemoglobin, collagen, trypsin, insulin
receptor, glycogen phosphorylase, plasma lipoproteins, and DNA polymerase in this course. Many
of these proteins and enzymes are the targets of poisons and drugs whose actions also will be
discussed.

B. Polysaccharides.

Polysaccharides are polymers of simple sugars known as monosaccharides (e.g., glucose).

Different polysaccharides perform either structural (cellulose) or energy storage (glycogen, starch)
functions. Polysaccharide and monosaccharides were some of the first biomolecules that were
studied by organic chemists. You should be familiar with the different types of representations
used to describe the structures of monosaccharides. A comparison of the polysaccharides starch
and cellulose provides an excellent example of how structure is crucial to biological function.
Namely, the structure of the glycosidic bonds linking the glucose units in cellulose and starch are
very similar, yet the subtle difference in bond configuration determines whether the polymer is
digestible (starch) or not (cellulose). We will spend a number of lectures on polysaccharide and
general carbohydrate metabolism. The medical relevance of these topics cannot be
overemphasized. For example, more than 1 in 30 Americans will become diabetic during their
lifetimes and suffer consequences attributable to energy imbalance and monosaccharide-based
tissue damage.

C. Nucleic acids.

Nucleic acids are composed of nucleotide monomer units. Nucleotides themselves are
composed of a monosaccharide, a nitrogenous base, and one or more phosphate groups (Fig. 1.8).
The nucleotide ATP is the major energy currency of the cell which is used to power a huge variety
of energy-requiring reactions. ATP and other ribonucleotides (containing ribose) also make up the
biopolymer RNA. Deoxyribonucleotides (containing deoxyribose) make up DNA. All nucleotides
are held together by phosphodiester linkages where one phosphate group is attached to 2 sugar
units in the backbone of the polymer (Fig. 1.9). Nucleotides play key roles in information transfer
in all organisms (DNA ® RNA ® protein). RNA also can carry out structural and enzymatic
functions. For example, the formation of peptide bonds during protein synthesis actually is
performed by one of the RNA constituents of the ribosome. In addition the main structural
component of ribosomes is RNA. Lastly, a number of nucleic acid analogs are used to inhibit DNA
synthesis and are extremely important in management of cancers and virally caused diseases such
as AIDS.

D. Lipids and membranes.

Lipids are a diverse collection of biomolecules that are composed mostly of carbon and
hydrogen, i.e., hydrocarbons. Lipids contain relatively few polar functional groups. They typically
are more soluble in organic solvents than in water. The primary building block of many lipids is a
fatty acid. The most common structural lipid in cell membranes--glycerophospholipid-
-contains 2 fatty acids, glycerol and a polar head group. When collected as assemblies of millions
of molecules, the classical biological structure known as a membrane is formed (Fig. 1.13).
Biological membranes usually contain proteins, and protein content and composition is highly
 variable and determined by membrane function. Although discussed here along with true
biopolymers, membranes are actually molecular aggregates. In later chapters, we will cover the
functions of membrane-bound proteins, enzymes and receptors. We'll discuss how membranes
serve as the primary sites of energy production in aerobic tissues such as the brain and liver, how
membrane-bound hormone receptors signal metabolic changes in cells, and how many toxins act
to impair membrane protein function.

IV. The energetics of life.

Living organisms are highly complicated at the molecular level. A large amount of energy is
invested in maintaining the ordered and complicated state of cells and tissues. In humans and
animals, energy needed for work and biosynthesis of cellular structures is derived from organic
molecules in the diet. Often these come from plant sources, who derived their energy for synthesis
of biomolecules from sunlight. In animals, energy is derived from the breakdown of fuel molecules
by processes referred to as catabolism. In turn, the energy released from catabolism is used to drive
biosynthetic processes collectively referred to as anabolism.
The flow of energy in biological systems is covered in the discipline known as
bioenergetics. Bioenergetics is a sub-discipline of classical thermodynamics, which has been
covered in your physics courses. Most of our use of thermodynamics will be concerned with the
calculation of free energy changes (∆G) which can be used to determine the direction of metabolic
reactions and their equilibrium constants. ∆G values are determined by the enthalpy (∆H, heat
transfer) and entropy (∆S, change in randomness) changes associated with a reaction through the
equation ∆G = ∆H - T∆S. Negative values of ∆G signify favorable reactions, whereas positive
values of ∆G are associated with unfavorable reactions. Keq is based on the DG value and gives
the ratio of products to reacts once equilibrium is reached. This is important because it will show
how a cell can ratio reactions in different directions. Kinetics measures the rate at which a reaction
takes place and how the reaction gets from start to finish. So reactions can be thermodynamically
favorable but kinetically unfavorable. So cells use enzymes that can only affect the kinetics not
the thermodynamics. Bioenergetics is one of the tools used in animal and human nutrition. Weight
gain or loss ultimately depend on the difference between caloric intake and expenditure. In this
course, we will discuss energy metabolism in different physiological states such as exercise and
fasting, and in diseases such as diabetes

V. Dehydration and Hydrolysis Reactions

Dehydration Synthesis

Most macromolecules are made from single subunits, or building blocks, called monomers. The
monomers combine with each other via covalent bonds to form larger molecules known as polymers.
In doing so, monomers release water molecules as byproducts. This type of reaction is known as
dehydration synthesis, which means “to put together while losing water. ” It is also considered to be a
condensation reaction since two molecules are condensed into one larger molecule with the loss of a
smaller molecule (the water.)

In a dehydration synthesis reaction between two un-ionized monomers, such as monosaccharide sugars,
the hydrogen of one monomer combines with the hydroxyl group of another monomer, releasing a
molecule of water in the process. The removal of a hydrogen from one monomer and the removal of a
hydroxyl group from the other monomer allows the monomers to share electrons and form a covalent
bond. Thus, the monomers that are joined together are being dehydrated to allow for synthesis of a
larger molecule.
A dehydration synthesis reaction involving un-ionized moners..: In the dehydration synthesis reaction
between two molecules of glucose, a hydroxyl group from the first glucose is combined with a hydrogen
from the second glucose, creating a covalent bond that links the two monomeric sugars
(monosaccharides) together to form the dissacharide maltose. In the process, a water molecule is
formed.

When the monomers are ionized, such as is the case with amino acids in an aqueous environment like
cytoplasm, two hydrogens from the positively-charged end of one monomer are combined with an
oxygen from the negatively-charged end of another monomer, again forming water, which is released
as a side-product, and again joining the two monomers with a covalent bond.

As additional monomers join via multiple dehydration synthesis reactions, the chain of repeating
monomers begins to form a polymer. Different types of monomers can combine in many
configurations, giving rise to a diverse group of macromolecules. Three of the four major classes of
biological macromolecules (complex carbohydrates, nucleic acids, and proteins), are composed of
monomers that join together via dehydration synthesis reactions. Complex carbohydrates are formed
from monosaccharides, nucleic acids are formed from mononucleotides, and proteins are formed from
amino acids.

There is great diversity in the manner by which monomers can combine to form polymers. For example,
glucose monomers are the constituents of starch, glycogen, and cellulose. These three are
polysaccharides, classified as carbohydrates, that have formed as a result of multiple dehydration
synthesis reactions between glucose monomers. However, the manner by which glucose monomers
join together, specifically locations of the covalent bonds between connected monomers and the
orientation (stereochemistry) of the covalent bonds, results in these three different polysaccharides with
varying properties and functions. In nucleic acids and proteins, the location and stereochemistry of the
covalent linkages connecting the monomers do not vary from molecule to molecule, but instead the
multiple kinds of monomers (five different monomers in nucleic acids, A, G, C, T, and U
mononucleotides; 21 different amino acids monomers in proteins) are combined in a huge variety of
sequences. Each protein or nucleic acid with a different sequence is a different molecule with different
properties.

Hydrolysis Reactions

Polymers are broken down into monomers in a process known as hydrolysis, which means “to split
water,” a reaction in which a water molecule is used during the breakdown. During these reactions, the
polymer is broken into two components. If the components are un-ionized, one part gains a hydrogen
atom (H-) and the other gains a hydroxyl group (OH–) from a split water molecule. This is what happens
when monosaccharides are released from complex carbohydrates via hydrolysis.
 Hydrolysis reaction generating un-ionized products.: In the hydrolysis reaction shown here, the disaccharide
maltose is broken down to form two glucose monomers with the addition of a water molecule. One glucose gets a
hydroxyl group at the site of the former covalent bond, the other glucose gets a hydrogen atom. This is the reverse
of the dehydration synthesis reaction joining these two monomers.

If the components are ionized after the split, one part gains two hydrogen atoms and a positive charge, the other
part gains an oxygen atom and a negative charge. This is what happens when amino acids are released from protein
chains via hydrolysis.

Hydrolysis reaction generating ionized products.: In the hydrolysis reaction shown here, the dipeptide is broken
down to form two ionized amino acids with the addition of a water molecule. One amino acid gets an oxygen atom
and a negative charge, the other amino acid gets two hydrogen atoms and a positive charge. This is the reverse of
the dehydration synthesis reaction joining these two monomers.

These reactions are in contrast to dehydration synthesis (also known as condensation) reactions. In dehydration
synthesis reactions, a water molecule is formed as a result of generating a covalent bond between two monomeric
components in a larger polymer. In hydrolysis reactions, a water molecule is consumed as a result of breaking the
covalent bond holding together two components of a polymer.

Dehydration and hydrolysis reactions are chemical reactions that are catalyzed, or “sped up,” by specific enzymes;
dehydration reactions involve the formation of new bonds, requiring energy, while hydrolysis reactions break
bonds and release energy.

In our bodies, food is first hydrolyzed, or broken down, into smaller molecules by catalytic enzymes in the
digestive tract. This allows for easy absorption of nutrients by cells in the intestine. Each macromolecule is broken
down by a specific enzyme. For instance, carbohydrates are broken down by amylase, sucrase, lactase, or maltase.
Proteins are broken down by the enzymes trypsin, pepsin, peptidase and others. Lipids are broken down by lipases.
Once the smaller metabolites that result from these hydrolytic enzymezes are absorbed by cells in the body, they
are further broken down by other enzymes. The breakdown of these macromolecules is an overall energy-releasing
process and provides energy for cellular activities.

Sources:

Libretexts. (2021, April 12). 1.9: Functional Groups. Biology LibreTexts.

https://bio.libretexts.org/Courses/University_of_California_Davis/BIS_2A%3A_Introductory_Biolo
gy_%28Britt%29/01%3A_Readings/1.09%3A_Functional_Groups
Libretexts. (2022a, June 9). 2.24: Synthesis of Biological Macromolecules - Dehydration Synthesis. Biology
LibreTexts.
https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_General_Biol
ogy_(Boundless)/02%3A_The_Chemical_Foundation_of_Life/2.24%3A_Synthesis_of_Biological_
Macromolecules_-_Dehydration_Synthesis
Libretexts. (2022b, June 9). 2.25: Synthesis of Biological Macromolecules - Hydrolysis. Biology LibreTexts.
https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_General_Biol
ogy_(Boundless)/02%3A_The_Chemical_Foundation_of_Life/2.25%3A_Synthesis_of_Biological_
Macromolecules_-_Hydrolysis
Molecular Biology | College of Agriculture, Life Sciences and Natural Resources | University of Wyoming.
(2022). DEPARTMENT OF MOLECULAR BIOLOGY. https://www.uwyo.edu/molecbio/