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Chapt. 39
Ch. 39
Student Learning Outcomes:
• Explain basic synthesis of nonessential amino acids
• Uses glucose derivatives (glycolysis, TCA)
• N sources often other aa
• Describe important cofactors:
• PLP (from Vitamin B6) for transaminations
• FH4 (tetrahydrofolate) for 1C;
• BH4 (tetrahydrobiopterin) for hydroxylation
• (Phe → Tyr)
• Explain general regulation of amino acid synthesis
(feedback inhibition, transcription inhibition)
• Degradation of aa often distinct from synthesis path
Overview synthesis of nonessential amino acids
Overview synthesis of nonessential amino acids:
• Met donates the S to Cys
• C skeletons come from glucose, glycolysis, TCA compounds
• Aa that can be synthesized are often used for other N cmpds:
•
•
•
Gly → purine, pyrimidine
Asp → purine, pyrimidine
Gln → neurotransmitter
Fig. 39.1*
Overview Degradation of amino acids
Overview: degradation of amino acids:
A. Gluconeogenic: Pyruvate, TCA intermediates
B. Ketogenic: Acetyl CoA, ketone bodies
Fig. 2
Some genetic disorders of amino acid metabolism
Degradation
path
enzyme
disease
symptoms
PKU classic
alcaptonuria
mental retardation
black urine, arthritis
Phe
phe hydroxylase (PAH)
homogentisate oxidase
Tyr
fumarylacetoacetate hydrolase tyrosinemia I
tyrosine aminotransferase
tyrosinemia II
Met
cystathionase
cystathionine b-synthase
cystathionuria benign
homocystinemia cardiovascular,
neurological
Gly
glycine transaminase
(Gly → oxalate)
oxaluria type 1 renal failure
Ca-oxalate stones
liver failure, death
neurological
Metabolism of Phe/Tyr
Phe and Tyr:
• PKU from absence PAH (autosomal
recessive); 1/104 births; all babies tested;
give special diet of low Phe (essential aa)
High Phe in blood → neurological
• Tyr is made from Phe
various defects in degradation
neurological, liver failure
Fig. 39.15
Cysteine metabolism
Cysteine metabolism:
• C, N from Ser, S from Met
• Met donates S to Cys via Homocys
•
Removal of –CH3
• Cystathionine precursor of Cys
• Feedback regulation of synthase
•
Adjust for dietary Cys
• Lack of synthase → homocyst(e)inemia
Figs. 39.6 Cys