Proteins, Amino Acids, Enzymes, and Nucleic Acids: Cellular Functions

Posted on Dec 18, 2024 in Biology

Proteins

Proteins are the most abundant organic molecules in cells, making up 50% or more of their dry weight. They are found in all parts of all cells, as they are fundamental in all aspects of cellular structure and function. There are many different kinds of proteins, each specialized for a different biological function. Moreover, most genetic information is expressed by proteins. They belong to the class of peptides and are composed of amino acids linked together by peptide bonds. A peptide bond is the union of the amino group (-NH₂) of an amino acid with the carboxyl group (-COOH) of another amino acid through the formation of an amide. Proteins are the basic constituents of life; their name derives from the Greek word “proteios,” which means “first.” In animals, proteins account for about 80% by weight of dehydrated muscles, about 70% of the skin, and 90% of dried blood. Proteins are also present in plants.

The importance of proteins, however, is related to their functions in the body rather than their quantity. All known enzymes, for example, are proteins. Often, enzymes exist in very small portions. Yet, these substances catalyze all metabolic reactions and enable organizations to build other molecules—proteins, nucleic acids, carbohydrates, and lipids—that are necessary for life.

Composition

All proteins contain carbon, hydrogen, nitrogen, and oxygen, and nearly all contain sulfur. Some proteins contain additional elements, particularly phosphorus, iron, zinc, and copper. Their molecular weight is extremely high. All proteins, regardless of their function or species of origin, are built from a basic set of twenty amino acids arranged in several specific sequences.

Function

They perform different functions, such as:

• Catalytic converters
• Structural elements (collagen) and contractile systems
• Storage (ferritin)
• Transport vehicles (hemoglobin)
• Hormones
• Anti-infectious (immunoglobulin)
• Enzymatic (lipases)
• Nutrition (casein)
• Protective agents

Because proteins carry a wide variety of functions in the cell, they can be divided into two major groups:

• Dynamic: Transportation, consumption, catalysis reactions, control of metabolism, and contraction, for example
• Structural: Proteins such as collagen and elastin, for example, promoting the structural support of cells and tissues

Classification of Proteins

On Composition

• Simple Proteins: Release only amino acids upon hydrolysis.
• Conjugated Proteins: Release amino acids plus a non-peptide radical, called a prosthetic group, upon hydrolysis. Examples include metalloproteins, hemeproteins, lipoproteins, and glycoproteins.

The Number of Polypeptide Chains

• Monomeric Proteins: Made up of only one polypeptide chain.
• Oligomeric Proteins: Made up of more than one polypeptide chain; these proteins have a more complex structure and function.

The Form

• Fibrous Proteins: Most fibrous proteins are insoluble in aqueous solvents and have very high molecular weights. They are usually formed by long molecules more or less rectilinear and parallel to the fiber axis. This category includes structural proteins, such as collagen in connective tissue, keratin in hair, sclerotin in the seed coat of arthropods, conchiolin in the shells of mollusks, and fibrin in blood serum or muscle myosin. Some fibrous proteins, however, have a different structure, such as tubulins, which are composed of multiple globular subunits arranged spirally.
• Globular Proteins: Have a more complex spatial structure and are more or less spherical. They are generally soluble in aqueous solvents, and their molecular weights range between 10,000 and several million. This category includes active proteins such as enzymes and transporters such as hemoglobin.

Amino Acids

Amino acids are the building blocks of the body. Besides building cells and repairing tissue, they form antibodies to combat invading bacteria and viruses. They are part of the enzyme and hormonal systems, they build nucleoproteins (RNA and DNA), they carry oxygen throughout the body, and they participate in muscle activity. When proteins are divided (separated or broken) during digestion, the result is 22 known amino acids. Eight amino acids are essential (cannot be made by the body), and the rest are non-essential (can be manufactured by the body with proper nutrition).

Amino acids are organic molecules formed by atoms of carbon (C), hydrogen (H), oxygen (O), and nitrogen (N). Some may contain sulfur in their composition. These compounds bind to form a molecule of amino acid as follows:

All amino acid molecules contain a carboxyl group (COOH), an amine group (NH₂), and a molecule of hydrogen (H) connected to a carbon atom called the alpha carbon. Also connected to that same carbon is a radical, generally called R. This radical varies with the amino acid; that is, each of the 20 existing amino acids contains its own radical, which can range from a single hydrogen atom (H), such as in glycine, to more complex groups. Amino acids are joined through peptide bonds to form proteins. For cells to produce their proteins, they need amino acids, which can be obtained from the diet or produced by the body.

Natural Amino Acids

Also called non-essential amino acids, these are produced by the body. The animal organism can produce only 12 of the 20 amino acids that exist in nature; the others are obtained from food. Plants, however, can produce all 20 amino acids.

Essential Amino Acids

These are amino acids that animals cannot produce but are required to manufacture proteins, so they must be obtained from food.

Not all foods contain all the amino acids, so the diet should be diversified. Foods rich in essential amino acids are of animal origin: meat, eggs, milk, cheese, etc. Plants do not have all the essential amino acids, so a vegetarian diet needs to be well diversified.

Peptides

Peptides are compounds or molecules formed by the union of amino acids. The combination of peptides is between the carboxyl group and an amino group of another amino acid, always releasing a water molecule. The mechanism that links the amino acids is called a peptide bond.

Peptides are classified according to the number of amino acids present in each compound:

• Two amino acids – dipeptide
• Three amino acids – tripeptide
• Four amino acids – tetrapeptide

Also, according to the number of amino acids present in biomolecules, we can sort the peptides into oligopeptides, when there are two to ten amino acids, and polypeptides, when there are eleven or more amino acids.

Enzymes

Enzymes are complex proteins (or derived heteroproteins) that act as catalysts in biological processes. Thus, the reactions that occur in living organisms are catalyzed by enzymes. In many cases, the intracellular enzymes are called endoenzymes. In other cases, they work outside of the cell that produced them, hence being called extracellular enzymes or exoenzymes. They are easily destroyed by heat (temperatures above 70ºC), severe agitation, ultraviolet and ultrasound waves, substances such as sodium cyanide, sodium fluoride, traces of heavy metals, acids, and bases, etc. Regarding their action, the most accepted theory is that the enzyme and the substance on which it will act (called the substrate) form an intermediate compound that subsequently suffers a breakdown, regenerating the enzyme. See a graph showing the catalytic action of the enzyme: the catalytic action of enzymes (lock and key model). They are highly specific catalysts; that is, for each substrate, there should be few (or only) enzymes. The classification is made from the name of the substrate on which the enzyme acts, followed by the termination ase. For example, urease catalyzes the hydrolysis of urea, and maltase catalyzes the hydrolysis of maltose.

Nucleic Acids

General Concepts

• Molecules with the storage function and expression of genetic information
• There are basically 2 types of nucleic acids:
  • Deoxyribonucleic acid – DNA
  • Ribonucleic acid – RNA

Nucleic acids are macromolecules formed by the connection between type 5 phosphodiester nucleotides, the fundamental units.

Nucleotides

• Are the fundamental units of nucleic acids
• Bind to each other through phosphodiester bonds, forming chains too long, up to millions in length
• In addition to participating in the structure of nucleic acids, nucleotides also act as components in the structure of important coenzymes in oxidative metabolism of the cell and as a form of chemical energy – ATP, for example.
• Also serve as activators and inhibitors in several important pathways of intermediary metabolism of the cell

Structure of Nucleotides

Nucleotides are molecules formed by:

• A pentose
• A nitrogenous base
• One or more radical phosphate

Nitrogenous Bases

Belonging to 2 families of compounds, and are 5 in total:

• Purines: Adenine and Guanine
• Pyrimidines: Cytosine, Thymine, and Uracil

Both DNA and RNA have the same purines and the pyrimidine base cytosine.

Thymine exists only in DNA, and in RNA, it is replaced by uracil – which has one less methyl group.

In some types of viral DNA and transfer RNA, unusual bases may appear.

The Pentoses

The addition of a pentose to a nitrogenous base produces a nucleoside.

The nucleosides A, C, G, T, and U are called, respectively, Adenosine, Cytidine, Guanosine, Thymidine, and Uridine.

If the sugar is ribose, we have a ribonucleoside, characteristic of RNA.

If the sugar is deoxyribose – less than 1 hydroxyl in C2 – we have a deoxyribonucleoside, characteristic of DNA.

The link with the nitrogenous base always occurs through the hydroxyl of the anomeric carbon of the pentose.

Phosphate

The addition of one or more phosphate radicals to the pentose through an ester link with the hydroxyl of carbon 5 of the same gives rise to nucleotides.

The phosphate groups are responsible for the negative charges of the nucleotides and nucleic acids.

The addition of the second or third phosphate group occurs in sequence, giving rise to nucleotide di- and triphosphates.

DNA

• It is present in the nucleus of eukaryotic cells, mitochondria, and chloroplasts, and in the cytosol of prokaryotic cells.
• In germ cells and the fertilized egg, it directs the development of the whole body from the information contained in its structure.
• It is doubled each time a somatic cell divides.

DNA Structure

DNA is a polydeoxyribonucleotide formed by thousands of nucleotides linked together by 3′, 5′-phosphodiester bonds.

The molecule is formed by a double-stranded antiparallel coiled on itself to form a double helix.

The Phosphodiester Bond

• Occurs between the phosphate on carbon 5 of the pentose of one nucleotide and the hydroxyl of carbon 3 of the pentose of the following nucleotide.
• The resulting string is very polar and has:
  • A 5′ end -> phosphate on carbon 5 of free pentose
  • A 3′ end -> hydroxyl of carbon 3 of free pentose

By convention, the bases of a sequence are always described from the 5′ to the 3′ end.

The phosphodiester bonds can be broken down enzymatically by enzymes called nucleases, which are divided into:

• Endonucleases -> They break links in the middle of the molecule
• Exonucleases -> They break connections at the ends of the molecule

The Double Helix

In the double helix of DNA, first described by Watson and Crick, the molecule chains fold around a common axis in an antiparallel way – the 5′ end of one chain is paired with the 3′ end of another chain. In the most common type of helix – “B” – the hydrophilic phosphate pathway is on the outside, while the hydrophobic bases, fixed to the skeleton, are on the inside of the structure. The structure resembles a “spiral staircase.”

There is base-pairing between the strands of the DNA molecule. Thus, we have matched:

• Adenine with Thymine -> AT
• Cytosine with Guanine -> CG

The bases remain paired by hydrogen bonds, 2 between “A” and “T” and 3 between “C” and “G”.

The strands of DNA can be separated under certain experimental conditions without disruption of the phosphodiester bonds, and the double helix can be denatured in a controlled and temperature-dependent process.

There are 3 forms of structural DNA:

• Form “B” -> Described by Watson and Crick in 1953 and as mentioned above, is the most common form; the helix is oriented to the right and has around 10 residues, with plans to base perpendicular to the helical axis.
• Form “A” -> Obtained by moderate dehydration of form “B,” it is also directed to the right but has about 11 residues, and the bases are at an angle of 20 degrees to the helical axis.
• Form “Z” -> The helix is turned in this form to the left and contains about 12 residues around.

The transition between the forms of DNA may play an important role in regulating gene expression.

RNA

It acts as a sort of “working copy,” created from the template DNA and used in the expression of genetic information. The synthesis of an RNA molecule from a DNA template is called “transcription.”

In this transcript, changes may occur on the transcribed RNA molecule, converting it from a faithful copy to a working copy of DNA.

Structure of RNA

Compared to DNA, 4 differences are important: RNA has uracil instead of thymine in the sequence of bases.

The Pentose in RNA is Ribose

RNA is composed of a single strand, with the possible intra-base-pairing. The RNA molecule is much smaller than that of DNA.

There are 3 types of RNA, each with structural and functional characteristics:

Ribosomal RNA

Or rRNA, is found in association with several different proteins in the structure of ribosomes, the organelles responsible for protein synthesis.

Corresponds to 80% of total cell RNA.

Transfer RNA

Carrier or RNA, or tRNA;

It is the smallest molecule of the 3 types of RNA and is linked specifically to each of the 20 amino acids found in proteins.

Corresponds to 15% of total cell RNA.

They make extensive intra-base-pairing and act in the positioning of amino acids in the sequence provided by the genetic code during protein synthesis.

Messenger RNA

Corresponds to only 5% of total cell RNA.

Acts by carrying the genetic information of the eukaryotic cell nucleus to the cytosol, where protein biosynthesis occurs.

It is used as a template in this biosynthesis.

Organization of Eukaryotic Genetic Material

The total DNA of a cell measures, on average, 1 meter in length!

For such a great volume of genetic material to fit within the cell nucleus, the DNA interacts with a large number of proteins.

These proteins have key roles in the organization and mobilization of genetic material.

Histones

Histones are small basic proteins rich in lysine and arginine and positively charged at physiological pH, which are associated with the DNA molecule.

Their positive charges, in association with the cation Mg²⁺, facilitate this connection with the negative DNA skeleton and stabilize the joint.

There are 5 classes of histones: H1, H2A, H2B, H3, and H4.

Nucleosomes

Are considered building blocks of chromosomes.

They consist of 8 histone molecules: 2 H2A, 2 H2B, 2 H3, and 2 H4, forming a regular octamer on which the double-stranded DNA wraps, almost 2 turns per nucleosome.

The nucleosomes are linked together by segments of “binding” DNA of about 50 nucleotides in length, forming the polynucleosomes or nucleofilaments.

After several levels of spatial organization, anchored by several types of proteins, we reach the final structure of chromosomes.

Histone H1 does not participate in the structure of nucleosomes but binds to “binding” DNA and participates in the process of compression of the structures.