building blocks for protein synthesis precursors of nucleotides and heme source of energy neurotransmitters precursors of neurotransmitters and hormones Outline of amino acid degradation The liver is the major site of degradation for most amino acids but muscle and kidney dominate the degrad ID: 775046
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Slide1
Amino acid metabolism
Slide2Metabolic uses of amino acids
building blocks for protein synthesis
precursors of nucleotides and heme
source of energy
neurotransmitters
precursors of neurotransmitters and hormones
Slide3Outline 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
Slide4Amino acid breakdown pathways join mainstream carbon utilization at different points of entry
Slide5Transamination of amino acids
Slide6The reaction mechanism of transamination
Slide7The ping pong bi bi mechanism of transamination
Slide8Nitrogen 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
Slide9The urea cycle, part 1: carbamoylphosphate synthetase
Slide10The urea cycle, part 2: subsequent reactions
Slide11The urea cycle in context
Slide12The urea cycle spans mitochondria and cytosol
Slide13The glucose-alanine cycle
Slide14Nitrogen transport by glutamine
Slide15The central role of glutamate in nitrogen disposal
Slide16Control of ammonia levels in the liver lobule
Slide17Regulation of the urea cycle
Slide18Hereditary 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
Slide19Asparagine degradation
Slide20Serine dehydratase
Slide21Serine-pyruvate transaminase
Slide22Degradation of leucine
Slide23Degradation of phenylalanine and tyrosine
Slide24Phenylketonuria (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
Slide25The Guthrie test for diagnosing phenylketonuria
Slide26Ochratoxin A inhibits phenylalanyl-tRNA synthetase
Slide27Tyrosinemia
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