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 FH 4 (tetrahydrofolate) for 1C; BH 4 (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 Fig. 39.1* 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

Overview Degradation of amino acids Fig. 2 Overview: degradation of amino acids: A.Gluconeogenic: Pyruvate, TCA intermediates B. Ketogenic: Acetyl CoA, ketone bodies

Some genetic disorders of amino acid metabolism Degradation pathenzymediseasesymptoms Phephe hydroxylase (PAH)PKU classicmental retardation homogentisate oxidasealcaptonuriablack urine, arthritis Tyrfumarylacetoacetate hydrolase tyrosinemia I liver failure, death tyrosine aminotransferasetyrosinemia IIneurological Metcystathionasecystathionuriabenign cystathionine b-synthasehomocystinemia cardiovascular, neurological Glyglycine transaminaseoxaluria type 1renal failure (Gly → oxalate) Ca-oxalate stones

Metabolism of Phe/Tyr Fig Phe and Tyr: PKU from absence PAH (autosomal recessive); 1/10 4 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

Cysteine metabolism Figs Cys Cysteine metabolism: C, N from Ser, S from Met Met donates S to Cys via Homocys Removal of –CH 3 Cystathionine precursor of Cys Feedback regulation of synthase Adjust for dietary Cys Lack of synthase → homocyst(e)inemia