Biochemistry: an Introduction

Content
Introduction and Scope of Biochemistry
Objectives of Biochemistry
Outcomes of the Course
Amino acids: characteristics and the main classes

Introduction and Scope of Biochemistry
Biochemistry is the branch of life science which deals with the study of chemical reactions occurring in living cells and organisms.
The term “Biochemistry” was first introduced by the German Chemist Carl Neuberg in 1903.
It studies the nature of the chemical constituents of living matter, their transformations in biological systems and the energy changes associated with these transformations.
Biochemistry is a discipline in which biological phenomena are analyzed in terms of chemistry. Biochemistry for the same reason, has been variously named as “Biological Chemistry or Chemical Biology.
Carl Neuberg

Subject of biochemistry
Biological chemistry is the science of the molecular/chemical essence of life.
It studies:
the chemical nature of the substances that make up living organisms,
their transformations, as well as
the relationship of these transformations with the activity of cells, organs and tissues and the whole body.

In other words, biochemistry studies the processes of development and functioning of organisms in the language of molecules, the structure and chemical processes that provide a life to single and multicellular creatures that inhabit the Earth.
The objects of biochemistry are various living organisms:
viruses
bacteria
plants,
Animals, and
human organism.

Biochemistry consists of several sections
1. Static biochemistry studies the chemical composition of organisms and the structure of their constituent molecules: (proteins, amino acids, nucleic acids, nucleotides, carbohydrates and their derivatives, lipids, vitamins, hormones).
2. Dynamic biochemistry studies the chemical reactions that represent the metabolism (metabolism), namely the pathways of the transformation of molecules and the mechanisms of the reactions between them.
Simple molecules and their derivatives (monosaccharides, fatty acids, amino acids, nucleotides, etc.) formed during the metabolism are called metabolites.

3. Functional biochemistry studies the biochemical reactions that underlie physiological functions.
It studies the biochemical basis of digestion of nutrients in the gastrointestinal tract; mechanisms of muscle contraction, nerve impulse conduction, blood respiratory function, regulation of acid-base balance, liver and kidney function, immune system, etc.

Following sections of biochemistry are also distinguished by the areas of research: Technical biochemistry (molecular basis of baking, cheese making, winemaking, etc.);
Medical/clinical biochemistry or human biochemistry (biochemical processes in the human body are normal and with pathology),
Evolutionary biochemistry (evolution of metabolism in the framework of the evolution of living organisms);
Enzymology (structure, properties and mechanism of action of enzymes), etc.

Outcomes of the “Biochemistry” Course
As a result of studying the discipline, the student will be able to:
1. demonstrate knowledge of the main classes of biological substances (their structure, properties);
2. demonstrate an understanding of the relationship between biological function and molecular structure;
3. to systematize and generalize knowledge about the Сhemical Сomposition of cells / tissues, the structure of substances that make up living organisms;
4. Understand metabolic reactions, energy transformation processes in living organisms;
5. To apply the basic methods of biochemical research;
6. Conduct a qualitative and quantitative analysis of biological material;
7. Work with biochemical equipment and apparatus;
9. Demonstrate experimental research skills.

Proteins
Almost all processes in living organisms are associated with the functioning of proteins and nucleic acids.
Proteins are molecular machines, building blocks, and living cell weapons.
Proteins account for at least half the dry weight of a living cell.
In living organisms, they perform a wide variety of functions (building, catalytic, storage, transport, motor, energy, regulatory, protective) and serve as those molecular tools by which genetic information is realized.
Each organism is characterized by a unique set of proteins.
The human body contains about 50,000 individual proteins. Each individual protein differs from all other proteins in structure and function. The total protein content in an adult is approximately 15 kg.
And the E.coli cell contains about 3,000 different proteins.

Proteins Are Built from a set of 20 Amino Acids
Amino acids are the building blocks of proteins.
An α-amino acid consists of a central carbon atom, called the a carbon, which is bonded to an amino group, a carboxylic acid group, a hydrogen atom, and a side chain, called the R group.
Each kind of amino acid has a different R group.

The common amino acids of proteins have been assigned three-letter abbreviations and one-letter symbols (Table 3-1), which are used as shorthand to indicate the composition and sequence of amino acids polymerized in proteins.
The three-letter code is transparent, the abbreviations generally consisting of the first three letters of the amino acid name. The one-letter code was devised by Margaret Oakley Dayhoff, considered by many to be the founder of the field of bioinformatics. The one-letter code reflects an attempt to reduce the size of the data files (in an era of punch-card computing) used to describe amino acid sequences.

Most Amino Acids Exist in Two Mirror-Image Forms
With four different groups connected to the tetrahedral α-carbon atom, α-amino acids are chiral: they may exist in one or the other of two mirror-image forms, called the l isomer and the d isomer (Figure 1).
Only l amino acids are constituents of proteins (some fungi are able to utilize d amino acids).

All Amino Acids Have at Least Two Charged Groups
Free amino acids in solution at neutral pH exist predominantly as dipolar ions (also called zwitterions). In the dipolar form, the amino group is protonated (NH3+) and the carboxyl group is deprotonated (COO−). The ionization state of an amino acid varies with pH (Figure 2).
In acid solution (e.g., pH 1), the amino group is protonated (NH3+) and the carboxyl group is not dissociated (−COOH).
As the pH is raised, the carboxylic acid is the first group to give up a proton.
The dipolar form persists until the pH approaches 9, when the protonated amino group loses a proton.
Under physiological conditions (near pH 7.0), amino acids exist in the dipolar form.

In acid solution (e.g., pH 1), the amino group is protonated (NH3+) and the carboxyl group is not dissociated (−COOH).
As the pH is raised, the carboxylic group gives up a proton.
The dipolar form persists until the pH approaches 9, when the protonated amino group loses a proton.
Under physiological conditions (near pH 7.0), amino acids exist in the dipolar form.
Figure 2. Ionization state as a function of pH. The ionization state of amino acids is altered by a change in pH

Amino Acids Contain a Wide Array of Functional Groups
Twenty types of side chains varying in size, shape, charge, hydrogen-bonding capacity, hydrophobic character, and chemical reactivity are commonly found in proteins. Many of these properties are conferred by functional groups (Table).
The amino acid functional groups include alcohols, thiols, thioethers, carboxylic acids, carboxamides, and a variety of basic groups. Most of these groups are chemically reactive.
All proteins in all species – bacterial, archaeal, and eukaryotic – are constructed from the same set of 20 amino acids with only a few exceptions.
The remarkable range of functions mediated by proteins results from the diversity and versatility of these 20 building blocks.

Classification of amino acids
Although there are many ways to classify amino acids, we will assort these molecules into four groups, on the basis of the general chemical characteristics of their R groups:
Hydrophobic amino acids with nonpolar R groups;
Polar amino acids with neutral R groups but the charge is not evenly distributed;
Positively charged amino acids with R groups that have a positive charge at physiological pH (pH ≈ 7.4);
Negatively charged amino acids with R groups that have a negative charge at physiological pH.

1. Hydrophobic amino acids with nonpolar R groups
Hydrophobic amino acids have mainly Hydrocarbon Side Chains.
The amino acids having side chains consisting only of hydrogen and carbon are hydrophobic.
The simplest amino acid is glycine, which has a single hydrogen atom as its side chain. With two hydrogen atoms bonded to the α-atom, glycine is unique in being achiral.
Alanine, the next simplest amino acid, has a methyl group (−CH3) as its side chain.
The three-letter abbreviations and
one-letter symbols under the names
of the amino acids depicted in Figures.

Larger aliphatic side chains are found in the branched-chain amino acids valine, leucine, and isoleucine. Methionine contains a largely aliphatic side chain that includes a thioether (−S−) group.
The different sizes and shapes of these hydrocarbon side chains enable them to pack together to form compact structures with little empty space.

Proline also has an aliphatic side chain, but it differs from other members of the set of 20 in that its side chain is bonded to both the a-carbon and the nitrogen atom. Proline markedly influences protein architecture because its ring structure makes it more conformationally restricted than the other amino acids.
Two amino acids with simple aromatic side chains are also classified as hydrophobic.
Phenylalanine, as its name indicates, contains a phenyl ring attached in place of one of the methyl hydrogen atoms of alanine.
Tryptophan has an indole ring joined to a methylene (−CH2−) group; the indole group comprises two fused rings and an NH group.

2. Polar Amino acids
The next group of amino acids that we will consider are those that are neutral overall, yet they are polar because the R group contains an electronegative atom that hoards electrons. Three amino acids, serine, threonine, and tyrosine, contain hydroxyl (−OH) groups (Figure 3.4). The electrons in the O−H bond are attracted to the oxygen atom, making it partly negative, which in turn makes the hydrogen partly positive.
Serine can be thought of as a version of alanine with a hydroxyl group attached to the methyl group, whereas threonine resembles valine with a hydroxyl group in place of one of the valine methyl groups.
Tyrosine is similar to phenylalanine but contains a hydrophilic hydroxyl group attached to the large aromatic ring.
The hydroxyl groups on serine, threonine, and tyrosine make them more hydrophilic (water soluble) and reactive than their respective nonpolar counterparts.

Polar amino acids

3. Positively Charged Amino Acids are hydrophilic
Amino acids having positively charged side chains that render these amino acids highly hydrophilic (Figure 3.5).
Lysine and arginine have long side chains that terminate with groups that are positively charged at neutral pH.
Lysine is topped by an amino group and arginine by a guanidinium group.
The R groups of lysine and arginine have dual properties – the carbon chains constitute a hydrocarbon backbone, similar to the amino acid leucine, but the chain is terminated with a positive charge.

Histidine contains an imidazole group, an aromatic ring that also can be positively charged.
The imidazole group of histidine is unique in that it can be uncharged or positively charged near neutral pH, depending on its local environment.

4. Negatively Charged Amino acids have Acidic Side Chains
The two amino acids in this group, aspartic acid and glutamic acid, have acidic side chains that are usually negatively charged under intracellular conditions (Figure 3.7).
These amino acids are often called aspartate and glutamate.
In some proteins, these side chains accept protons, which neutralize the negative charge.
This ability is often functionally important.

Essential Amino Acids must Be obtained from the Diet
Most microorganisms can synthesize the entire basic set of 20 amino acids, whereas human beings can make only 11 of them.
Amino acids that cannot be generated in the body must be supplied by the diet and are termed essential amino acids.
The others are called nonessential amino acids (Table 3.2).
These designations refer to an organism under a particular set of conditions.
For example, a human adult can synthesize enough arginine to meet his or her needs, but a growing child requires more arginine than the body can provide to meet the protein-synthesis needs of rapid growth.

Uncommon Amino Acids also have important
Functions
In addition to the 20 common amino acids, proteins may contain residues created by modification of common residues already incorporated into a polypeptide – that is, through postsynthetic modification (Fig. 3-8a).
Among these uncommon amino acids are 4-hydroxyproline, a derivative of proline, and 5-hydroxylysine, derived from lysine. The former is found in plant cell wall proteins, and both are found in collagen, a fibrous protein of connective tissues.
6-N-Methyllysine is a constituent of myosin, a contractile protein of muscle.
Another important uncommon amino acid is γ-carboxyglutamate, found in the blood-clotting protein prothrombin and in certain other proteins that bind Ca2+ as part of their biological function.
More complex is desmosine, a derivative of four Lys residues, which is found in the fibrous protein elastin.
Selenocysteine and pyrrolysine are special cases. Selenocysteine contains selenium rather than the sulfur of cysteine.

Summary
1. Proteins Are Built from a set of 20 Amino Acids.
Proteins are linear polymers of amino acids.
Each amino acid consists of a central tetrahedral carbon atom that is bonded to an amino group, a carboxylic acid group, a distinctive side chain, and a hydrogen atom.
Only the l isomer exists in natural proteins.
All natural proteins are constructed from the same set of 20 amino acids.

2. Amino Acids Contain a Wide Array of Functional Groups.
The side chains of these 20 building blocks vary tremendously in size, shape, and the presence of functional groups. AA can be grouped as follows on the basis of the chemical properties of the side chains:
hydrophobic side chains: glycine, alanine, valine, leucine, isoleucine, methionine, proline, and the aromatic amino acids phenylalanine and tryptophan;
polar amino acids – serine, threonine, tyrosine, asparagine, and glutamine;
positively charged amino acids – lysine, arginine, and histidine; and
negatively charged amino acids – aspartic acid and glutamic acid.