1. Amino acid metabolism

2. Metabolic uses of amino acids
building blocks for protein synthesis
precursors of nucleotides and heme
source of energy
neurotransmitters
precursors of neurotransmitters and hormones

3. Outline of amino acid degradation
The liver is the major site of degradation for most amino acids, but muscle and kidney dominate the degradation of specific ones
Nitrogen is removed from the carbon skeleton and transferred to α-ketoglutarate, which yields glutamate
The carbon skeletons are converted to intermediates of the mainstream carbon oxidation pathways via specific adapter pathways
Surplus nitrogen is removed from glutamate, incorporated into urea, and excreted

4. Amino acid breakdown pathways join mainstream carbon utilization at different points of entry

5. Transamination of amino acids

6. The reaction mechanism of transamination

7. The ping pong bi bi mechanism of transamination

8. Nitrogen disposal and excretion
Nitrogen accruing outside the liver is transported to the liver as glutamine or alanine
In the liver, nitrogen is released as free ammonia
Ammonia is incorporated into urea
Urea is released from the liver into the bloodstream and excreted through the kidneys

9. The urea cycle, part 1: carbamoylphosphate synthetase

10. The urea cycle, part 2: subsequent reactions

11. The urea cycle in context

12. The urea cycle spans mitochondria and cytosol

13. The glucose-alanine cycle

14. Nitrogen transport by glutamine

15. The central role of glutamate in nitrogen disposal

16. Control of ammonia levels in the liver lobule

17. Regulation of the urea cycle

18. Hereditary enzyme defects in the urea cycle
may affect any of the enzymes in the cycle
urea cannot be synthesized, nitrogen disposal is disrupted
ammonia accumulates, as do other metabolites depending on the deficient enzyme
treatment
protein-limited diet
arginine substitution
alternate pathway therapy

19. Asparagine degradation

20. Serine dehydratase

21. Serine-pyruvate transaminase

22. Degradation of leucine

23. Degradation of phenylalanine and tyrosine

24. Phenylketonuria (PKU)
homozygous defect of phenylalanine hydroxylase
affects one in 10,000 newborns among Caucasians; frequency differs with race
excess of phenylalanine causes symptoms only after birth; intrauterine development normal
cognitive and neurological deficits, probably due to cerebral serotonin deficit
treatment with phenylalanine-restricted diet
some cases are due to reduced affinity of enzyme for cofactor THB, can be treated with high dosages of THB

25. The Guthrie test for diagnosing phenylketonuria

26. Ochratoxin A inhibits phenylalanyl-tRNA synthetase

27. Tyrosinemia homozygous defect of fumarylacetoacetate hydrolase
fumarylacetoacetate and preceding metabolites back up
fumaryl- and maleylacetoacetate react with glutathione and other nucleophiles, causing liver toxicity
the drug NTCB inhibits p-hydroxyphenylpyruvate dioxygenase, intercepting the degradative pathway upstream of the toxic metabolites
dietary restriction of tyrosine required to prevent neurological deficit