Amino Acids and Protein Synthesis

• Amino acids serve as building blocks for peptides and proteins.
• Proteins consist of hundreds of amino acids linked by peptide bonds, forming a long chain.
• Proteins can be visualized as a string of beads, with each bead representing an amino acid.
• Proteins are synthesized from 20 L-α-amino acids, encoded by nucleotide triplets called codons.
• One- and three-letter abbreviations represent sequences of peptides and proteins.
• Genetic information from DNA is transcribed into mRNA and then translated into a protein's amino acid sequence.
• The general structure of amino acids includes an NH3-CH-COO- group and a variable side chain.
• An amino acid consists of a constant H₂N-CH(R)-COOH, where R is the side chain
• At neutral pH, the H2N- group is protonated to H3N+-, and the -COOH group is deprotonated to -COO-.

Standard Amino Acids

• Proteins comprise 20 standard amino acids.
• The central alpha (α)-carbon atom is covalently bonded to a carboxylic acid group, an amino group, and a hydrogen atom.
• Proline is an exception because it has a secondary amino group.

Amino Acid Classification

• Standard amino acids are those encoded by the universal genetic code.
• Non-standard amino acids are incorporated via unique synthetic mechanisms.
  • Selenocysteine is incorporated when mRNA includes a SECIS element, causing the UGA codon to encode selenocysteine.
  • Pyrrolysine is used by methanogenic archaea and coded for by the UAG stop codon.
  • Proline possesses an imino acid where a-amine is a secondary amine with the alpha nitrogen being covalently bonded to both the alpha-carbon and a side chain, as opposed to being a primary amine.
• The incorporation of amino nitrogen into the five-membered ring reduces structural flexibility of polypeptide regions containing proline.
• Selenocysteine is the 21st protein L-α amino acid, where a selenium atom replaces sulfur of its elemental analog, cysteine.
• Selenocysteine isn't a product of posttranslational modification but is directly inserted during translation, charged on a special tRNA specific for the UGA (STOP) codon.

Other Classes of Amino Acids

• Non-protein amino acids are not encoded by the genetic code but are intermediates in metabolic pathways, i.e., ornithine and citrulline in urea biosynthesis.
• Non α-amino acids: -NH2 is not attached to the α-carbon, i.e., γ-aminobutyric acid (GABA) and β-alanine.
• Modified protein amino acids are modified after incorporation into proteins.

Amino Acid Requirements

• Essential amino acids are not synthesized in the body and must be obtained through the diet.
• Non-essential amino acids are synthesized in the body, thus there is no dietary requirement.
• Semi-essential amino acids are not synthesized in adequate amounts and require dietary supplementation.

Metabolic Classifications of Amino Acids

• Ketogenic amino acids catabolically yield intermediates convertible into acetyl-CoA or acetoacetyl-CoA (ex. Lysine and Leucine).
• Glucogenic amino acids give rise to intermediates of glycolysis or Krebs cycle convertible into glucose (ex. Arginine and Histidine).
• Mixed amino acids are catabolized to produce glycolytic intermediates as well as acetyl-CoA derivatives (ex. Phenylalanine and Tryptophan).

Amino Acid Classifications Based on Side Chain Groups

• Functional group R group leads to classifications as:
  • Aliphatic
  • Aromatic
  • Acidic
  • Basic
  • Acid amide
  • Sulfur-containing
  • Cyclic
• Based on functional group, amino acids are:
  • Polar
  • Non-polar
• Based on site of attachment of functional group, amino acids are classified as:
  • Alpha
  • Beta
  • Gamma
  • Delta
• Non-polar amino acids such as glycine, alanine, valine, leucine, isoleucine, methionine and proline are classified as hydrophobic (R = alkyl).
• Phenylalanine and tryptophan are nonpolar amino acids (R = aromatic group)
• Hydrophillic amino acids are:
  • Neutral: Tyrosine, Serine, Threonine, Cysteine, Glutamine, Asparagine
  • Acidic: Glutamic acid, Aspartic acid
  • Basic: Lysine, Histidine, Arginine.

Properties of Essential Amino Acids

• Phenylalanine functions as a precursor for tyrosine, dopamine, epinephrine, norepinephrine and melanin.
  • Phenylketonuria is a genetic disorder where the body cannot metabolize phenylalanine due to a lack of phenylalanine hydroxylase.
• Tryptophan acts as a precursor to neurotransmitters(serotonin), hormones(melatonin), and vitamin niacin, and along with tyrosine residues anchor membrane proteins within cell membranes.
  • Fructose malabsorption can lead to an improper absorption of tryptophan in the intestine, causing a reduced level of blood tryptophan.
• Alanine is synthesized from pyruvate and branched-chain amino acids, with a role in the glucose-alanine cycle between tissues and the liver.
  • The alanine cycle helps to remove pyruvate and glutamate from muscle and safely transports them to the liver.
  • Alterations in the alanine cycle can increase levels of alanine transferases which are linked to type II diabetes.
• Valine is essential for hematopoietic stem cell self-renewel.
  • In sickle-cell disease, glutamic acid is replaced with valine due to hydrophobicity makes Hb protein prone to abnormal aggregation.
• Primary metabolic end products of leucine metabolism are acetyl-CoA and acetoacetate, and muscle/adipose tissue use leucine for sterol formation.
  • Maple Syrup Urine Disease is caused by a deficiency of branched-chain α-keto acid dehydrogenase complex that leads to the accumulation of branched chain amino acids and ketoacids in the urine and blood.
• Isoleucine has diverse physiological functions, such as wound healing, nitrogenous waste detoxification, immune stimulation, and hormone secretion.
• Homocysteine can be used to regenerate methionine or form cysteine.
• Methionine is a substrate for other amino acids such as cysteine and taurine, S-adenosyl methionine and the antioxidant glutathione.
  • Improper conversion of methionine may lead to atherosclerosis because of accumulation of homocysteine.

Polar Uncharged Amino Acids

• Threonine is susceptible to numerous posttranslational modifications
  • the hydroxyl side-chain undergoes O-linked glycosylation and phosphorylation.
  • Phosphorylated threonine(phosphothreonine)plays a role in cell signal transduction and neural activity.

Polar Charged Amino Acids

• Histidine is the precursor for histamine, an amine produced in the body necessary for inflammation.
  • Histidine ammonia-lyase converts histidine into ammonia and urocanic acid; a deficiency can lead to histidinemia.
• Lysine contributes to protein stability, epigenetic regulation, structural protein scaffolding, calcium homeostasis and fatty acid metabolism.
  • A second major role of lysine is epigenetic regulation through histone modification.
  • A lack of lysine catabolism results in the accumulation of amino acids in plasma, leading to hyperlysinaemia.

Summary of Key Points

• Both α- and non-α-amino acids occur in nature, but proteins are synthesized with L-α-amino acids.
• The unique biochemical functions of amino acids are determined by their R groups.
• Based on the composition and properties of their R groups, amino acids are classified as basic, acidic, aromatic, aliphatic, or sulfur-containing.

This quiz covers various aspects of amino acids and protein synthesis. Topics include selenocysteine incorporation, non-protein amino acids, collagen maturation, essential amino acids, amino acid classification, ketogenic amino acids, GABA, and amino acid location within proteins.