Amino Acids and Heart Disease Quiz

Learning Objectives

• Understand the functions of amino acids in bodily processes.
• Distinguish between essential and non-essential amino acids.
• Recognize the role of transaminase enzymes in amino acid metabolism.
• Describe how amino acids serve as substrates in gluconeogenesis, ketogenesis, and energy metabolism.
• Explain ureogenesis and the mechanism of amino nitrogen elimination.
• Examine OTC deficiency as a pathophysiological example.

Amino Acid Structure

• Amino acids consist of an α-carboxyl group, an α-amino group, and a side chain (R-group) that defines identity.
• The general formula: R-CH(COOH)-NH2.

Functions of Amino Acids

• Serve as building blocks for proteins: enzymes, receptors, hormones, and transport proteins.
• Precursor for smaller bioactive compounds:
  • Hemes from glycine.
  • Nucleic acids (purines and pyrimidines) from aspartate, glycine, and glutamine.
  • Hormones like thyroxine.
  • Neurotransmitters (dopamine, catecholamines, serotonin, glutamate).

Protein Turnover and Amino Acid Pool

• Average protein turnover includes approximately 12 kg in the body with around 100 g in circulation.
• Amino acid levels are maintained through tissue utilization and release from stores, chiefly in muscle and liver.

Amino Acid Degradation

• Degraded into two categories: glucogenic (precursors to glucose) and ketogenic (precursors to ketone bodies).
• Catabolism involves transamination, where amino groups are transferred, forming glutamate, acting as a universal amino donor.

Transamination

• Transamination reactions predominantly generate glutamate.
• Aminotransferase enzymes facilitate the process, named after the amino donor.
• Glutamate collects amino groups, allowing for amino acid degradation and synthesis.

Glucose-Alanine Cycle

• Alanine, synthesized in muscle via transamination, travels to the liver, where it is converted to glucose and urea.

Glutamate Dehydrogenase

• Converts glutamate to α-ketoglutarate, releasing ammonia.
• Facilitates nitrogen release, providing carbon skeletons for gluconeogenesis.
• Reaction direction is influenced by substrate concentrations and allosteric control (ATP inhibits, ADP activates).

Ammonia

• Neurotoxin; hyperammonaemia leads to slurred speech, blurred vision, tremors, mental confusion, and potential coma.
• Disposal occurs via the urea cycle in the liver.
• Sources of ammonia include transamination, urea breakdown by gut bacteria, and purine/pyrimidine metabolism.

Transport of Nitrogen to Liver

• Glutamine synthetase converts glutamate and ammonia into glutamine for transport to the liver.
• Alanine is converted to pyruvate and glutamate in the liver, contributing to gluconeogenesis.

Urea Cycle

• Urea synthesized in the liver is water-soluble and excreted via the kidneys.
• Processes four substrates (aspartate, NH3, CO2) and five enzymes, with carbamoyl phosphate synthase as the rate-limiting step.

Pathophysiological Example: OTC Deficiency

• OTC deficiency is an X-linked disorder causing hyperammonaemia, presenting with anorexia, irritability, and lethargy.
• Treatments include a low-protein diet, medications for nitrogen excretion, and potential liver transplant.

Amino Acid Classification

• Essential amino acids: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine.
• Semi-essential: arginine, histidine (essential for children).
• Non-essential: alanine, asparagine, aspartate, cysteine, glutamate, glutamine, proline, serine, glycine, tyrosine.

Synthesis of Non-Essential Amino Acids

• Various metabolic intermediates and enzymes facilitate the synthesis of non-essential amino acids from essential ones and other precursors.

Cysteine and Methionine Metabolism

• Cysteine is synthesized from methionine and serine; methionine is necessary for sulfur supply and links to cardiovascular health through homocysteine levels.

Overview of Protein Metabolism

• Proteins undergo proteolysis into amino acids or are synthesized from amino acids.
• Amino acid catabolism can yield substrates for gluconeogenesis or feed into the urea cycle for nitrogen removal.

Recommended Reading

• Lippincott’s Ch. 19 and 20; Meisenberg and Simmons Ch. 26 for deeper understanding of amino acid metabolism and biochemistry.