Amino Acids and Proteins Notes

Proteins and Amino Acids

Proteins Overview

• Proteins are polymers of amino acids linked by peptide bonds.

• Central dogma: DNA is transcribed into mRNA, which is then translated into protein.

  • $DNA \rightarrow mRNA \rightarrow Protein$

Proteins in the Human Body

• Immune System:

  • Antibodies: Fight invaders.

  • Complement System: A system of about 20 protein molecules activated during infections.

• Muscle:

  • Actin and Myosin: Interact for muscle movement.

  • Myoglobin: Releases oxygen to muscles.

  • Ferritin: Stores and releases oxygen.

• Blood:

  • Hemoglobin: Transports oxygen.

  • Fibrinogen: Clots blood.

  • Albumin: Maintains proper liquid amount in blood; also acts as a buffer by neutralizing excess hydrogen ions.

• Structural Proteins:

  • Cytoskeleton: Network of protein filaments and tubules maintaining cell shape.

  • Keratin: Found in skin, hair, and nails.

  • Collagen: Provides strength.

  • Elastin: Provides flexibility.

• Enzymes:

  • Digestive Enzymes: Help break down food.

• Cell Membrane:

  • Form channels for substances to move through.

  • Act as enzymes and receptors.

  • Three types: peripheral, integral, and lipid-bound proteins.

• Signaling Proteins:

  • Cytokines: Communicate with other cells.

Amino Acids Overview

• Amino acids are the building blocks of proteins.

• Over 300 amino acids are known in nature.

• 20 standard (α-amino acids) are coded for by DNA.

• Two functional groups:

  • Carboxylic acid (-COOH) group.

  • Amino group (-NH2) on the alpha (α) carbon.

• Different side groups (R) determine the behavior of amino acids.

Structure of Amino Acids

• 19 of the 20 amino acids follow a similar structural rule.

• Proline: An exception; it is an imino acid where the amino group and R group are linked, forming a cyclic secondary amino acid.

  • Proline terminates the secondary structure of proteins and is often found in turns or bends.

Chirality

• A carbon atom with four different functional groups in a tetrahedral configuration is asymmetric (chiral carbon).

• Amino acids exist in two enantiomer forms (optical isomers).

• All amino acids except glycine (achiral) exhibit optical isomerism.

• Chirality leads to D and L forms (levorotatory and dextrorotatory).

Stereoisomerism

• Isomeric molecules have the same molecular formula and sequence of bonded atoms but differ in the three-dimensional orientations of their atoms.

• Enantiomers are stereoisomers that are mirror images of each other, having the same physical properties.

• Amino acids found in proteins are L configuration; D-amino acids are found in bacteria.

• Geometry of proteins affects reactivity (e.g., substrate binding in enzymes).

Amino Acids: Functions

• Body Proteins:

  • Proteosynthesis: 250-400 g/day

  • Degradation

• Dietary Proteins:

  • Digestion into amino acids

• Amino acid conversion (carbon skeleton) can lead to:

  • Glucose through glycolysis.

  • Acetyl CoA and ketone bodies.

• Non-protein derivatives include porphyrins, purines, pyrimidines, neurotransmitters, hormones, complex lipids, and aminosugars.

• Transamination, Krebs cycle, and urea cycle are also involved.

Standard and Non-Standard Amino Acids

• Standard amino acids: Found in proteins.

  • Glycine, Alanine, Valine, Leucine, Isoleucine

  • Cysteine, Methionine, Serine, Threonine

  • Tyrosine, Phenylalanine, Tryptophan

  • Histidine, Arginine, Lysine

  • Glutamic acid, Glutamine

  • Aspartic acid, Asparagine

  • Proline

• Non-standard amino acids: Not found in proteins.

  • Citrulline and Ornithine: Intermediates in urea synthesis.

  • Dihydroxyphenylalanine (DOPA): Precursor of melanin and catecholamines.

  • Thyroxine: A thyroid hormone.

Classification of Amino Acids

• Based on:

  • Side chain

  • Polarity

  • Metabolic function

  • Nutritional requirement

• Classes:

  • Aliphatic: Gly, Ala, Val, Leu, Ile

  • Sulfur: Cys, Met

  • Aromatic: Phe, Tyr, Trp

  • Hydroxyl: Ser, Thr, (Tyr)

  • Acidic: Asp, Glu

  • Basic: Lys, Arg, His

  • Imino: Proline

Specific Amino Acid Characteristics

• Hydrophobic, neutral, aliphatic:

  • Glycine: Achiral and smallest amino acid.

  • All aliphatic amino acids are nonpolar.

  • Proline: Secondary amino acid (imino acid).

  • Valine, Leucine, and Isoleucine: Branched-chain amino acids.

• Sulfur-containing:

  • Cysteine: Used to make disulfide bonds and is a component of Glutathione peptide (detoxifying agent and free radical scavenger).

  • Methionine: S-adenosyl Methionine is a methyl donor in biochemical reactions. Homocysteine is derived from methionine metabolism.

  • Disulfide Bond: Formed from oxidation of cysteine residues.

• Aromatic:

  • Tryptophan: R group is called indole ring.

  • Aromatic amino acids absorb UV light around 280 nm (Tryptophan 280nm, Tyrosine 274nm, Phenylalanine 257nm).

  • Used to quantify proteins and separate proteins from other cell contents.

• Hydroxyl-containing:

  • Serine and Threonine: Used for O-linked glycosylation of proteins.

  • Tyrosine of glycogenin protein is used for O-glycosidic linkage to synthesize glycogen.

• Acidic Groups and Their Amides (Polar):

  • Aspartic acid (Asp) and Glutamic acid (Glu).

  • Asparagine (Asn) and Glutamine (Gln) are uncharged amides.

  • Asparagine is used for N-linked glycosylation.

    • $Asparagine + Sugar \rightarrow N-Glycosidic bond$

• Basic Groups (Polar):

  • Arginine (Arg), Lysine (Lys), and Histidine (His).

• Acidic vs. Basic Side Chains:

  • Acidic: Aspartic acid and glutamic acid contain carboxylic acid in side-chains and are proton donors. Side-chains carry a negative charge at physiologic pH.

  • Basic: Lysine and arginine contain amino groups and accept protons. Side-chains are protonated (positively charged) at physiologic pH. Due to positive charges, they are main components of histone proteins.

• Hydrogen-bonding:

  • Serine, threonine, tyrosine (with hydroxyl group).

  • Asparagine and glutamine (with an amide group).

• Attachments for other compounds:

  • Phosphate group: Hydroxyl group of serine, threonine, tyrosine.

  • Oligosaccharides in Glycoproteins: Amide group of asparagine and hydroxyl group of serine and threonine.

• Hydrophobic Interactions:

  • Help stabilize the 3-D shape of the protein.

  • Differ in soluble and membrane-associated proteins.

Classification Based on Polarity

• Nonpolar:

  • Aliphatic: Glycine, Alanine, Valine, Leucine, Isoleucine.

  • Sulfur-containing: Methionine.

  • Aromatic (except tyrosine): Phenylalanine, Tryptophan.

  • Imino acid: Proline.

• Polar:

  • Hydroxyl-containing: Serine, Threonine, Tyrosine.

  • Cysteine

  • Asparagine, Glutamine

Nutritional Classification

• Essential Amino Acids: Cannot be synthesized by the body; must be obtained from the diet. (PVT TIM HALL: Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Arginine, Lysine).

  • No HISsy fits, No ARGuing & No Lying for the BASIC training HALL.

  • Leucine, Isoleucine, and Valine are branched-chain amino acids.

• Non-Essential Amino Acids: Can be synthesized by the body; do not need to be obtained from the diet.

Metabolic Function Classification

• Glucogenic amino acids

• Ketogenic amino acids

• Both glucogenic and ketogenic amino acids

• This classification helps to understand how different amino acids contribute to energy metabolism in the body.

Acidic & Basic Properties of Amino Acids

• An acid is a proton donor; a base is a proton acceptor.

• Amino acids are amphoteric molecules.

  • α-COOH is a weak acid group, and α-NH3+ is a weak basic group.

  • Exist in protonic equilibrium.

  • Some R groups are ionizable.

    • R-COOH <--------> R-COO^- + H^+

    • R-NH3^+ <---------> R-NH2 + H^+

  • R-COOH is a far stronger acid than R-NH3+.

  • At physiologic pH (7.4), carboxyl groups exist as COO- and amino groups as NH3+.

  • Molecules that contain equal numbers of ionizable groups of opposite charge and therefore bear no net charge are termed zwitterions.

Zwitterions

• A molecule with functional groups, of which at least one has a positive and one has a negative electrical charge.

• The net charge of the entire molecule is zero.

• Amino acids are the best-known examples, containing an amine group (basic) and a carboxylic group (acidic).

Buffers

• An acid-base conjugate pair (such as acetic acid and acetate ion) resists changes in pH.

• A plot of the dependence of the pH of solution on the amount of OH- or H+ added is called a titration curve.

• The net charge on an amino acid is the algebraic sum of all the positively and negatively charged groups present.

• Depends on pKa of its functional groups and pH of the surrounding medium.

Isoelectric pH

• Isoelectric species is the form of the molecule that has an equal number of positive and negative charges and thus is electrically neutral.

• Isoelectric pH (pI) is the pH midway between pKa values on either side of the isoelectric species.

• For an amino acid like alanine, which contains two ionizable groups (an α-carboxyl group and a protonated α-amino group):

  • The pKa of the α-COOH group is 2.3, whereas that of the α-NH3+ group is 9.1.

  • $pI = \frac{pK<em>1 + pK</em>2}{2}$

    • $pI = \frac{2.3 + 9.1}{2}= 5.7$

Albumin as a Buffer

• Albumin works as a buffer in the blood by neutralizing excess hydrogen ions and maintaining the body's acid-base balance.

• Albumin, abundant in blood plasma, contains histidine residues.

• Histidine's buffering capacity is effective within a pH range close to physiological pH (around 6-8).

• Albumin can bind and transport other substances, including hydrogen ions (H+), further enhancing its buffering ability.

Practice Questions

• Q.1. Which one among the following amino acids is optically inactive?

  • b. Glycine

• Q2. A distinctive side chain determines the property of an amino acid. Which side chain group of serine helps in the activity of an enzyme active site?

  • c. Hydroxy group

• Q3. Lysine and arginine are proton accepters at physiological pH. This property of the amino acids is due to which one of the following side chains?

  • d. Basic

• Q4. Which of the following amino acids is aromatic, essential, as well as both glucogenic and ketogenic?

  • d. Tryptophan

• Which of the following groups of amino acids contain side-chain hydroxyl groups

  • B. Serine, threonine, and tyrosine