MBBS 1: Amino Acid Metabolism

Amino Acid Metabolism

• Amino acids are required as building blocks for proteins, neurotransmitters, creatine, carnitine, haem, purines, and pyrimidines.
• They act as a source of blood glucose in fasting and starvation.

Protein Turnover and Dynamic Equilibrium

• Body proteins are continuously degraded to amino acids and re-synthesized.
• Average turnover in an adult is 300g-400g per day.
• Turnover is variable, and most proteins have half-lives of several days.
• Structural proteins (e.g., collagen) may have half-lives of years.
• Hormones and digestive enzymes are degraded very rapidly, with half-lives of minutes.

Amino Acid Pools

• Free amino acids are present in very low concentrations inside cells or in the bloodstream.
• They are constantly mixed and exchanged with other free amino acids distributed throughout the body.

Nitrogen Balance

• In normal healthy adults, the total amount of nitrogen taken in the diet as protein should be equal to the amount of nitrogen excreted from the body in the form of urea, uric acid, creatinine, and NH4+.
• The subject is then described as being in nitrogen balance.
• Positive nitrogen balance occurs when protein synthesis exceeds the rate of breakdown, and is seen during normal growth in children, convalescence after serious illness, after immobilization, and in pregnancy.
• Negative nitrogen balance occurs when protein breakdown exceeds synthesis, and is seen in starvation, serious illness, late stages of some cancers, and injury.

Essential Amino Acids

• There are 20 amino acids commonly found as 'building blocks' of proteins.
• Plants and microorganisms can synthesize all 20 amino acids from NH3 and CO2.
• Humans can synthesize only 10 amino acids from other intermediates and rely on dietary sources for the remaining 10.
• The 10 essential amino acids are valine, methionine, lysine, phenylalanine, leucine, isoleucine, threonine, tryptophan, histidine, and arginine.

Pathways of Protein Degradation

• Most cellular proteins are removed by the ubiquitin breakdown system or by endocytosis and autophagocytosis.
• Foreign proteins are taken into vesicles by endocytosis or autophagocytosis, which fuse with lysosomes, and are degraded by proteolytic enzymes.

Transamination and Deamination

• The N part of the amino acid is removed by transfer to an acceptor molecule, resulting in an oxo acid.
• The released NH2 group can be converted to ammonia (NH3) or NH4+.

Amino Acid Degradation

• After losing their amino groups, most of the 20 amino acids become oxo acids.
• Oxo acids can be metabolized by the TCA pathway to CO2 and H2O, providing a source of ATP.
• In starvation, the carbon skeletons of 13 of the amino acids can be converted back to glucose by the liver, and are classified as 'glucogenic'.
• Leucine and lysine can only be degraded to acetyl CoA and are classified as 'ketogenic'.
• Phenylalanine and tyrosine can be catabolized with part of their chemical structure being converted into glucose, and are classified as both glucogenic and ketogenic.

Role of the Liver in N Metabolism

• The liver removes amino acids, glucose, and fats from the portal blood supply.
• Absorbed amino acids are used for synthesis of cellular proteins, plasma proteins, haem, purines, and pyrimidines.
• The liver degrades excess amino acids by trans-deamination and converts NH3 to urea for excretion through the urea cycle.

Central Role of the Liver

• The liver is the only organ that can convert the amino groups of amino acids to urea for excretion from the body.
• The amino groups (NH2) are transported as glutamine in the bloodstream.
• Glutamine can carry 2 ammonia equivalents to the liver for urea formation and can deliver ammonium ions to the kidney for pH regulation.

Importance of Glutamine

• Glutamine is a safe carrier of ammonia in the blood.
• Ammonia is toxic to the brain.

The Urea Cycle

• The urea cycle (ornithine cycle) is the pathway by which the liver converts ammonia into urea.
• End products of nitrogen metabolism include urea, creatinine, uric acid, and ammonia (NH4+).

Impaired Conversion of NH3 to Urea

• Hyperammonaemia can occur due to liver failure, genetic defects, or reduction in catalytic activity of any enzyme of the urea cycle.
• Treatment for hyperammonaemia involves finding out the cause and addressing it accordingly.

This quiz covers the concepts of protein turnover, nitrogen balance, and amino acid classification, as well as the pathways of protein degradation. It's a great resource for MBBS 1 students studying biochemistry.