Amino Acid and DNA Metabolism (Biochemistry)

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Amino Acid and DNA Metabolism

Human body has no stores of nitrogen or amino acids.

Cannot synthesise 8 essential amino acids: leucine, isoleucine, methionine, threonine, valine, lysin, phenylalanine and tryptophan.

Conditionally essentially amino acids: histidine and arginine.

Urea synthesis:

Ammonia and carbon dioxideare taken up in the mitochondria and react to form carbamic acid. Carbamoyl phosphateformed from carbamic acid by carbamoyl phosphate synthetase I.

Urea cycle:

  • 1     Ornithine is converted to citruline via ornithine transcarbamoylase. Carbamoyl phosphate goes in and Pi is produced (by-product).
  • 2.       Citruline is converted to arginosuccinate via arginosuccinate synthetase. Aspartate and ATP go in and ADP + Pi are produced as by-products.
  • 3.       Arginosuccinate is converted to arginine via arginosuccinase. Fumarate given off; used in Krebs Cycle.
  • 4.       Arginine is converted back into ornithine via arginase. Water goes in and Urea is given off. 

a-ketoglutarate complexconverts glutamate to aspartate, which is a part of Urea Cycle. Urea Cycle produces fumarate which can be converted into malate for Krebs’ cycle.

Total energy consumption is 1ATP as 3ATPs are produced from malate entering Krebs Cycle– which provides 1NADH.

Hyperammonaemia

Hyperammonaemia is the metabolic disturbance characterised by an excess of ammonia in blood. It is associated with anorexia and pain insensitivity.

Leads to brain oedemaand astrocyte swellingdue to accumulation of glutamine.

Theories: inhibition of glutaminase; deamination of a-ketoglutarateand inhibition of Krebs cycle; membrane dysfunction and increased permeability to K+ and Cl-.

Most common cause is liver damage.

Glutamate metabolism

Brain is very vulnerable to hyperammonaemia because glutamate and glutamine have central roles in amino acid metabolism.

Much of the…

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