Biological Functions of Proteins

• Amino acids, peptides, and proteins are central topics in biochemistry.
• Dr. Evans Nyaboga is with the Department of Biochemistry at the University of Nairobi.

Biological Functions of Proteins

• Proteins have several key roles in biological systems.
• Enzymes are specific proteins that catalyze virtually all chemical reactions in biological systems.
• Hemoglobin transports oxygen in erythrocytes, facilitating oxygen delivery throughout the body.
• Myoglobin carries and stores oxygen in muscle tissue, providing oxygen reserves for muscle activity.
• Albumin transports free fatty acids in the blood, ensuring their delivery to various tissues.
• Transferrin transports iron in the blood, essential for iron homeostasis.
• Actin and myosin are contractile proteins in muscle, enabling coordinated movement.
• Collagen provides structural and mechanical support as a fibrous protein in skin and bone.
• Clotting factors are essential for the defense function, preventing blood loss.
• Immunoglobulins protect against infections, defending the body against foreign invaders.
• Rhodopsin is a photoreceptor protein in retinal rod cells, enabling the generation and transmission of nerve impulses.
• Growth factor proteins control growth and differentiation processes in the body.
• Hormones such as insulin and thyroid-stimulating hormone also regulate growth and differentiation.

Protein Composition

• Proteins constitute about 50% of the dry weight of the human body, highlighting their significance.
• Unlike lipids and carbohydrates, proteins are not stored, necessitating their daily consumption.
• The recommended daily intake for adults is 0.8 grams of protein per kg of body weight, with children needing more.
• Dietary protein is obtained from sources like meat and milk.
• Approximately 100,000 different proteins exist within the human body, each with unique functions.
• Fibrous proteins are insoluble in water and used for structural purposes, exemplified by keratin and collagen.
• Globular proteins are more or less soluble in water and serve nonstructural roles.

Amino Acids: Building Blocks of Proteins

• Amino acids are the fundamental building blocks of proteins, linking together to form complex structures.
• Amino acids contain two functional groups: a carboxylic end (COOH) and an amino end (NH2) group.
• These functional groups are bonded to a central alpha (α) carbon atom, defining them as alpha amino acids.
• The alpha carbon is also bonded to a hydrogen atom and a unique side chain group (R).
• Each amino acid has a unique side chain (R), which dictates its specific properties.
• The side chain is characteristic of every amino acid.

Types of Amino Acids

• Essential to know the names, structures, three-letter codes, and one-letter codes.

Classifying Amino Acids:

• Amino acids can be classified based on their side chains (R groups).
• They can also be classified on biological/nutritional characteristics and metabolic fate.

Side Chain Classifications

• Amino acids can be hydrophobic (non-polar) or hydrophilic (polar).
• Hydrophilic amino acids may be uncharged, positively charged, or negatively charged.

Nonpolar (Hydrophobic) Amino Acids

• Side chains cannot participate in hydrogen or ionic bonds; instead, they form hydrophobic interactions.
• They are typically found in the interior of proteins in an aqueous environment.
• Include amino acids with aliphatic R groups, such as glycine and alanine.
• Also include amino acids with aliphatic branched R groups, like valine, leucine, and isoleucine.
• Amino acids with aromatic R groups are phenylalanine and tryptophan.
• Methionine contains a sulfur group with an amino acid.
• Proline is an example of an imino acid.

Polar (Hydrophilic) Amino Acids

• They contain functional groups, such as hydroxyl (-OH) and amide (-CONH2).
• Side chains can form hydrogen bonds with water, but cysteine is an exception.
• These amino acids are classified into polar charged, polar non-charged.
• Acidic amino acids (negatively charged) include aspartic and glutamic acid.
• Basic amino acids (positively charged group) include arginine, lysine, and histidine.
• Amino acids with OH groups include serine, threonine, and tyrosine.
• Cysteine contains an SH group.
• Amino acids with amide groups include glutamine and asparagine.

Biological/Nutritional

• Non-essential amino acids can be synthesized in the body from essential amino acids.
• Glycine, alanine, serine, tyrosine, cysteine, arginine, asparagine, aspartic acid, glutamic acid, glutamine, and proline are some examples.
• Essential amino acids cannot be synthesized in the human body and must be obtained through the diet.
• Valine, leucine, isoleucine, threonine, methionine, arginine, lysine, histidine, phenylalanine, and tryptophanare some examples
• Arginine and histidine are semiessential.

Metabolic Classifications of Amino Acids

• Amino acids are classified per their metabolic or degradation products.
• Ketogenic amino acids give rise to ketone bodies, and lysine and leucine are purely ketogenic.
• Mixed ketogenic and glucogenic amino acids yield both ketone bodies and glucose, like isoleucine, phenylalanine, tyrosine, and tryptophan.
• Glucogenic amino acids produce glucose, and other amino acids by catabolism yield products that enter glycogen and glucose formation.

Optical Activity

• Optical activity is the ability of a chiral (asymmetric) molecule to rotate the plane of plane-polarized light.
• A chiral molecule has an asymmetric carbon atom attached to four different groups.
• All amino acids except glycine are optically active because they have groups attached to the α-carbon
• Optically active molecules have two isomers (enantiomers) that are mirror images.
• Amino acid enantiomers are either D- or L-isomers, named based on the arrangement of COOH, R, NH2, and H groups around the chiral α-carbon atom.
• Arrange hydrogen atom away from the viewer, if the groups are arranged clockwise around the carbon atom, it is the D-form, counterclockwise, it is the L-form.
• All amino acids in proteins have the L-configuration.

Amphoteric Properties

• Amino acids have both basic and acidic groups, enabling them to act as either a base or an acid.
• There is an internal transfer of a hydrogen ion from the -COOH group to the -NH2 group forming zwitterions.
• Neutral amino acids exist in aqueous solution as Zwitterions, and contain both positive and negative charges.
• Zwitterions are electrically neutral and cannot migrate in an electric field.

Isoelectric Point (IEP, PI)

• The pH at which the zwitterion is formed when the number of positive and negative charges are equal.
• Zwitterions have minimum solubility at their IEP, allowing some amino acids to be isolated by precipitation at their IEP.

Peptides

• Formed when an amide bond links two amino acids, also known as peptide bond.

Types of Peptides

• Dipeptide: Contains two amino acids joined by a peptide bond.
• Tripeptide: Contains three amino acids joined by peptide bonds.
• Polypeptide: Contains many amino acids joined by peptide bonds.
• Protein: A biological macromolecule containing at least 40 amino acids joined by peptide bonds.

Naming Peptides

• C-terminal amino acid: At the end of the chain and contains free -COO- group, always written at the left.
• N-terminal amino acid: End of the chain having the free -NH3+ group, always written at the right).
• Begin naming from the N terminal end.
• Drop "-ine" or "-ic acid" and it is replaced by "-yl".
• Give the full name of amino acid at the C terminal.

Biologically Active Peptides

• Enkephalins are pentapeptides produced in the brain that act as pain killers and sedatives by binding to receptors.
• Addictive drugs morphine and heroin bind to theses receptors.
• Endorphins are polypeptides, and are known for reducing pain and mood enhancing effects.
• Oxytocin and vasopressin are cyclic nonapeptide hormones with identical sequences except for two amino acids.
• Oxytocin stimulates uterine muscle contraction and milk production.
• Vasopressin is an antidiuretic hormone (ADH) that targets the kidneys and limits urine production during dehydration.

Protein Structure

• Proteins are structured in 4 ways: primary, secondary, tertiary and quaternary.

Primary Structure

• Is the order of amino acids held together by peptide bonds
• The amino acids sequence is unique
• All bond angles are 120°, giving the protein a zigzag arrangement.
• The -SH (sulfhydryl) group of cysteine is easily oxidized to an -S-S- (disulfide).

Secondary Structure

• Describes the way the amino acids next to or near each other along the polypeptide are arranged in space.
• Alpha helix (α helix).
• Beta-pleated sheet (ẞ-pleated sheet).
• Triple helix (found in Collagen).
• Some regions are random arrangements,
• A section of polypeptide chain coils into a rigid spiral.
• Hel by H bonds
• Amino acids contains R- groups that point outward from the helix,
• Is typical of fibrous proteins such as silk.

Triple Helix

• Collagen is the most abundant protein
• It contains three polypeptide chains
• Present in connective tissues bone, teeth, blood vessels, tendons, and cartilage.
• High % of glycine allows the chains to lie close to each other
• We need vitamin C to form H-bonding (a special enzyme).

Tertiary Structure

• Is determined by attractions and repulsions between the side chains (R) of the amino acids in a polypeptide chain.
• The interactions between side chains of the amino acids fold a protein into a specific three-dimensional.
• Disulfide (-S-S-).
• salt bridge (acid-base).
• Hydrophilic (polar).
• hydrophobic (nonpolar).
• Hydrogen bond.

Globular Protein

• Has comapct, spherical shape.
• Almost solouble in water.
• Carry out the work of the cells:
• Myoglobin.
• Stores oxygen in muscles.
• 153 amino acids in a single polypeptide chain, mostly a-helix.

Fibrous Protein

• Has long, skinny shape, and is insoluble in water.
• Involve in the structure of cells and tissues.
• a-keratin: skin, nail, hair, and bone.
• b-keratin: feathers of birds.

Quaternary Structure

• It occurs when two or more protein units (polypeptide subunits) combine.
• Is stabilized by the same interactions found in tertiary structures (between side chains).
• Hemoglobin consists of four polypeptide chains as subunits.
• Is a globular protein and transports oxygen in blood .
• CO is poisonous because it binds 200 times more strongly to the Fe2+ than does O2.

Sickle Cell Hemoglobin

• A disease where a single amino acid of both B subunits is changed from glutamic acid to valine.
• The blood cell becomes elongated and crescent shaped (sickle).
• These red blood cells will rupture capillaries causing pain .