HUMAN BIOCHEMISTRY - L. V. Kapilevich - 2016

PART 1. SPORTS BIOCHEMISTRY

CHEMICAL COMPOSITION OF THE ORGANISM

The Human Body has the following chemical composition: Water - 60-65 %, Organic compounds - 30-32 %, Mineral Substances - 4 %.

Organic compounds are of paramount importance for living organisms. The most vital classes of organic compounds found in living organisms include Proteins, CARBOHYDRATES, Lipids, and Nucleic Acids.

Proteins

Proteins perform crucial Functions in the body, including Enzymatic Catalysis, TRANSPORT AND STORAGE, contraction and movement, immune defense, Intracellular Signaling, Metabolic Regulation, mechanical support, and energy production.

Cell/13.html">Protein Structure

Proteins are high-molecular-weight compounds (polymers) composed of Amino Acids—monomeric units linked together by peptide bonds. All 20 amino acids found in proteins share a common structure characterized by the presence of an amino group NН₂ and a carboxyl group СООН. Amino acids differ from one another by The structure of their R-group and, consequently, their properties. All Amino acids can be grouped based on the polarity of their R-groups, i.e., their ability to interact with water at physiological pH values.

Peptide bonds are formed through the interaction between the amino group of one Amino Acid and the carboxyl group of another: a peptide bond is a covalent amide bond that links amino acids into a chain.

A protein molecule has four LEVELS OF STRUCTURAL Organization.

The first level is the Primary Structure. The primary structure is defined by the order (sequence) of amino acids within the polypeptide chain. Even Peptides with identical length and Amino Acid Composition can be different substances because their Amino acid sequences vary. The Amino Acid Sequence of a protein is unique and genetically determined.

The second level of spatial organization is the Secondary structure (Fig. 1). Several types of secondary structure are known: the α-Helix, formed by intra-chain Hydrogen Bonds between the NH group of one amino acid residue and the CO group of the fourth residue downstream; the β-structure ( pleated sheet), formed by inter-chain hydrogen bonds or bonds between segments of a single polypeptide chain folded back on itself; and the random coil, which refers to regions lacking a regular, periodic spatial organization. However, the conformation of these regions is also strictly determined by The amino acid sequence. The proportion of α-helices and β-structures varies among proteins: Fibrous proteins contain exclusively α-helices or β-pleated sheets, whereas Globular proteins feature distinct polypeptide fragments that may form either α-helices, β-pleated sheets, or random coils. All three folding patterns of the polypeptide chain can coexist within the same protein.

Class="center">Fig. 1. Protein secondary structure (A - α-helix, B - β-pleated sheet)

The third level of spatial organization is the tertiary structure. It represents the three-dimensional orientation of a polypeptide chain containing α-helices, β-structures, and unstructured regions (random coils). Further folding of the coiled polypeptide chain yields a compact structure, which results primarily from interactions between the side chains of amino acid residues. This structure is stabilized by electrostatic forces, hydrogen bonds, hydrophobic interactions, and Disulfide Bonds.

The overall three-dimensional shape of a protein molecule is referred to as its conformation. Conformation is inherently unstable and easily alterable, which directly impacts the protein's biological functions. The conformation in which a protein exhibits biological activity is termed its Native State.

Only certain proteins possess a quaternary structure. Quaternary structure is a complex supramolecular assembly consisting of multiple polypeptide chains (subunits), each with its own primary, secondary, and tertiary structure. Each individual protein comprising The quaternary structure is called a subunit.

Subunits are assembled into the quaternary structure via weak non-covalent interactions (ionic, hydrogen, and Hydrophobic bonds); consequently, the quaternary structure is dynamic and readily dissociates into its constituent subunits.

Protein Classification

Several classifications of proteins exist, of which the following two are the most widespread:

1. Based on their composition, proteins are divided into simple (proteins proper) and conjugated (proteids). Simple proteins consist solely of amino acids (albumins, globulins, Histones, structural tissue proteins). Conjugated Proteins contain additional non-protein components. The non-protein moiety is designated as the prosthetic group, and the protein moiety as the apoprotein. For instance, Phosphoproteins contain phosphoric acid, Nucleoproteins contain nucleic acid, Glycoproteins contain a carbohydrate moiety, etc.

2. Classification based on spatial conformation. In this case, proteins are divided into two major classes: globular and fibrous. Globular protein molecules have a spherical or ellipsoidal shape; plasma albumins and globulins serve as classic Examples. Fibrous proteins form elongated, thread-like molecules, with Collagen being a prime example.

PHYSICOCHEMICAL PROPERTIES OF Proteins

1. Denaturation.

Protein molecules maintain their native (functional) conformation due to A large number of weak bonds and rapidly denature when environmental conditions change, which compromises the stability of these bonds. Variations in Temperature, Ionic strength, pH, as well as Treatment with organic Solvents or certain destabilizing agents can disrupt the native conformation, a process known as denaturation. Denaturing Agents form bonds with amino or carbonyl groups of the peptide backbone or specific amino acid side chains, replacing the protein's own intramolecular bonds and consequently altering its secondary and tertiary structures. These changes do not affect the primary structure, but they result in the loss of the protein's biological activity.

2. Renaturation.

Under specific conditions, a denatured protein can undergo renaturation (reversible denaturation). This occurs when the denaturing or destabilizing factor is removed. For instance, when urea is removed via dialysis, Polypeptides spontaneously restore their native conformation. The same phenomenon occurs during the slow cooling of a protein denatured by heat.

3. Molecular weight.

Proteins are high-molecular-weight compounds. For example, Ribonuclease ( an RNA-cleaving enzyme) consists of 124 amino acid residues and has a Molecular Weight of approximately 14,000. Myoglobin (a Muscle protein) contains 153 amino acid residues and has a molecular weight of 17,000, whereas Hemoglobin has a molecular weight of 64,500 (574 amino acid residues). Other proteins exhibit much higher molecular weights: globulin (which forms Antibodies) consists of 1,250 Amino Acids and has a molecular weight of about 150,000, while the molecular weight of the enzyme Glutamate dehydrogenase exceeds 1,000,000.

4. Amphotericity.

A crucial property of proteins is their ability to exhibit both acidic and basic properties, acting as amphoteric electrolytes. This is enabled by various dissociating groups located within the amino acid radicals. For instance, the acidic properties of a protein are conferred by the carboxyl groups of aspartic and glutamic amino acids, whereas its basic properties are due to the radicals of Arginine, Lysine, and Histidine. The higher the content of dicarboxylic amino acids in a protein, the more pronounced its acidic properties, and vice versa. In an alkaline environment, a protein releases a proton and acquires a negative charge, whereas in an acidic environment, the dissociation of acidic groups is suppressed, and the protein becomes a cation. Thus, the factor determining whether a protein behaves as a cation or an anion is the reaction of the medium, which depends on the hydrogen ion concentration and is expressed as the pH value.

However, at certain pH values, the number of positive and negative charges equalizes, making the molecule electroneutral, meaning it will not move in an electric field. This specific pH value of the medium is defined as the isoelectric point of proteins.

5. Solubility in water.

Proteins exhibit a high affinity for water, meaning they are hydrophilic. As charged particles, protein molecules attract water dipoles, which arrange themselves around the protein molecule to form an aqueous or Hydration shell. This shell protects protein molecules from aggregation and precipitation. The size of the hydration shell depends on the protein's structure.

6. Salting-out.

Proteins possess the property of reversible precipitation, meaning they precipitate out of solution under METABOLISM/18.html">The Influence of certain substances, after which they can return to their initial (native) state once these substances are removed. Alkali and alkaline-earth metal salts are used to salt out proteins (sodium sulfate and ammonium sulfate are most commonly used in practice). These salts strip away the hydration shell (causing dehydration) and neutralize the charge.

Nucleic acids

Nucleic acids perform the following functions in the human Organism: DNA is responsible for storing hereditary information, while RNA is involved in the expression of Genetic information and catalytic functions.

Structure of Nucleic Acids

Nucleic acids are linear polymers of nucleoside monophosphates, i.e., polynucleotides. NUCLEOTIDES consist of three components: a pyrimidine or purine base, a carbohydrate (pentose), and phosphoric acid. Nucleotides are linked together into a chain by phosphodiester bonds. These bonds are formed through the Esterification of the OH group at the C-3 position of the pentose in one nucleotide and the OH group of the phosphate residue in another nucleotide.

A nucleic acid molecule has two levels of structural organization.

The Introduction/19.html">Primary structure of nucleic acids is defined as The sequence of nucleotide residues in the polymer chain. The immense diversity of DNA and RNA molecules is explained by their primary structure.

The secondary structure differs between DNA and RNA molecules. A DNA molecule is a right-handed helix consisting of two antiparallel polynucleotide chains. This means that the 3' end of one chain corresponds to the 5' end of the other, and vice versa. The base residues are directed toward the interior of the helix. Each turn of the helix contains 10 Base Pairs. DNA chains are not identical because their nucleotide compositions differ; however, the primary structure of one chain predetermines The nucleotide sequence of the other, meaning they are complementary to each other. This is due to the existence of complementary base pairs. The physicochemical basis of complementarity relies on hydrogen bonds, which can form exclusively between adenine in one chain and thymine in the opposite chain (the A-T pair), and analogously between guanine and cytosine (the G-C pair).

An RNA molecule consists of a single polynucleotide chain. Certain segments of this chain (up to 20–30 nucleotide pairs) can be complementary to one another, forming a helical structure stabilized by bonds between adenine and uracil (the A-U pair) and guanine and cytosine (the G-C pair). Single-stranded loops are located between the helical regions. There are several types of RNA: Messenger RNA (mRNA), Transfer RNA (tRNA), and ribosomal RNA (rRNA).

Classification of nucleic acids

A single nucleic acid molecule can contain only one type of carbohydrate—either ribose or deoxyribose. Based on this, all nucleic acids are divided into two types: Ribonucleic Acids, or RNA (containing ribose), and Deoxyribonucleic Acids, or DNA (containing deoxyribose).

Physicochemical properties of nucleic acids

1. Denaturation.

The Secondary structure of DNA is stabilized solely by weak hydrogen and hydrophobic bonds; consequently, DNA is capable of denaturing (melting) when heated to 80–90 °C. During denaturation, the double-stranded DNA molecule separates into individual single strands. The temperature at which 50% of the DNA is denatured is called the melting temperature, which depends on the qualitative COMPOSITION OF THE DNA.

2. Renaturation.

If a solution of denatured DNA is cooled slowly (annealing), weak bonds re-form between the complementary strands, potentially yielding a helical structure identical to the original (native) one.

3. Solubility in water.

DNA forms viscous solutions in water; heating such solutions to 60 °С or treating them with alkalis causes The Double Helix to dissociate into its two constituent strands.

4. Molecular weight.

The molecular weight of nucleic acids varies widely, but overall it is very high, especially for DNA. The Nucleus of a human cell contains 46 DNA molecules, each composed of 3.5 billion mononucleotide pairs. Mitochondria contain circular DNA, with each molecule comprising 16 thousand mononucleotide pairs. The structure of Mitochondrial DNA was the first to be deciphered. It encodes the information for 13 polypeptide chains, 2 Ribosomal RNAs, and 22 Transfer RNAs.

Carbohydrates

Carbohydrates primarily serve an energetic function. The Main sources of energy are glucose and Glycogen. In addition, lipids, Certain amino acids, and pentoses can be synthesized from carbohydrates. Carbohydrates are also integral Structural and functional Components of the cell, such as Glycolipids and glycoproteins.

Structure of Carbohydrates

Carbohydrates are aldehyde alcohols, ketone alcohols, or their derivatives.

Classification of Carbohydrates

According to the modern classification, Carbohydrates are divided into three main groups: Monosaccharides, Oligosaccharides, and Polysaccharides.

Monosaccharides (simple sugars) do not undergo Hydrolysis, and it is impossible to derive simpler carbohydrates from them. Monosaccharides include ribose, deoxyribose, glucose, fructose, galactose, etc.

Oligosaccharides consist of several (up to 10) monosaccharides linked by covalent bonds. Upon hydrolysis, they break down into their constituent monosaccharide units. The most common are Disaccharides, such as sucrose (table or cane sugar), which contains glucose and fructose residues; lactose (milk sugar), consisting of glucose and galactose residues; and others.

Polysaccharides are long, unbranched or branched chains comprising hundreds or thousands of monosaccharides. Most commonly, polysaccharides are composed of glucose. The most widespread polysaccharides include Cellulose (fiber), starch, and glycogen. All of them consist exclusively of glucose residues.

Physicochemical Properties of Carbohydrates

1. Molecular weight.

Carbohydrates include both relatively simple compounds with a molecular weight of around 200 and giant polymers with molecular weights reaching several millions.

2. Solubility in water.

Monosaccharides are highly soluble in water and readily form syrups, making it quite difficult to isolate them in crystalline form.

3. Oxidation.

Like all aldehydes, The oxidation of monosaccharides yields the corresponding acids. For instance, oxidizing glucose with an ammoniacal silver oxide solution produces gluconic acid (the "silver mirror" reaction).

4. Reduction.

The reduction of sugars yields polyhydric alcohols. Hydrogen in the presence of nickel, lithium aluminum hydride, and other agents are used as reducing agents.

5. Alkylation (ether formation).

When treated with methyl alcohol in the presence of gaseous hydrogen chloride, the hydrogen atom of the glycosidic hydroxyl group is replaced by a methyl group.

6. Acylation (ester formation).

The reaction of glucose with acetic anhydride yields an ester, pentaacetylglucose.

Major carbohydrates in the human body

The primary natural carbohydrate is glucose, which can exist either in a free state (monosaccharide) or as a component of oligosaccharides (such as sucrose and lactose) and polysaccharides (such as cellulose, starch, and glycogen).

The empirical formula for glucose is C₆H₁₂O₆. However, as is well known, glucose can adopt various spatial Conformations (acyclic and cyclic). In the human body, almost all glucose—both free and incorporated into oligo- and polysaccharides—exists in the cyclic form.

Free glucose in the human body is primarily found in the Blood, where its concentration remains relatively constant, fluctuating within a narrow range of 3.0 to 6.1 mmol/L (70-110 mg %).

Another carbohydrate typical of humans and higher animals is glycogen. Glycogen consists of highly branched, large molecules containing tens of thousands of glucose residues. The empirical formula for glycogen is (C₆H₁₀O₅)_n (where C₆H₁₀O₅ represents a glucose residue).

Glycogen serves as a storage and reserve form of glucose. The primary glycogen reserves are concentrated in the Liver (up to 5-6% of liver mass) and in Muscles (up to 2-3% of muscle mass).

Glucose and glycogen perform an energetic function in the body, serving as the main sources of energy for all cellular components.

Lipids

The BIOLOGICAL FUNCTIONS OF lipids are determined primarily by their role as Energy Sources. This function is carried out by Fatty acids released during fat breakdown. Phospholipids, glycolipids, and Cholesterol participate in The formation of cell membranes. Derivatives of certain polyunsaturated fatty acids (Prostaglandins) perform a regulatory function, and these fatty acids represent essential dietary components. Cholesterol serves as a structural membrane component as well as a precursor for Bile acids and Steroid Hormones.

Structure of lipids

A fat molecule consists of a polyhydric alcohol residue and fatty acid residues joined by ester bonds.

Fatty acids that make up fats are divided into saturated (lacking double bonds) and unsaturated (containing one or more double bonds).

Fats of different origins differ from one another in their specific fatty acid composition.

Adipocytes (fat Cells) are composed of triglycerides. Biomembranes, in turn, incorporate phospholipids, glycolipids, and cholesterol.

Classification of Lipids

Lipids are subdivided into fats and fat-like substances (lipoids).

Physicochemical properties of lipids

1. Solubility.

Fats are insoluble in water, highly soluble in organic solvents, but generally poorly soluble in alcohol.

2. Hydrolysis.

When treated with superheated steam, mineral acids, or alkalis, fats undergo hydrolysis (saponification) to yield glycerol and fatty acids or their salts, thereby forming soaps. Vigorous agitation with water results in the formation of emulsions. An example of a stable fat-in-

water emulsion is milk. The emulsification of fats in the intestine—a prerequisite for their absorption—is facilitated by bile acid salts.

Review Questions

1. List the Major Classes of organic compounds found in living organisms.

2. What functions do proteins perform in the human body?

3. What type of bond stabilizes the primary structure of a protein molecule?

4. Give examples of globular proteins.

5. Describe the structure of DNA.

6. Give examples of polysaccharides.

7. In which human Organs are glycogen stores concentrated?

8. On what basis are fatty acids classified into saturated and unsaturated?

9. How much energy is released upon the oxidation of 1 g of fat?