Chapt. 39

Ch. 39Student 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

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 intermediatesB. Ketogenic: Acetyl CoA, ketone bodies

Some genetic disorders of amino acid metabolismDegradation path enzyme disease symptomsPhe phe hydroxylase (PAH) PKU classic mental retardation

homogentisate oxidase alcaptonuria black urine, arthritis

Tyr fumarylacetoacetate hydrolase tyrosinemia I liver failure, deathtyrosine aminotransferase tyrosinemia II neurological

Met cystathionase cystathionuria benigncystathionine b-synthase homocystinemia cardiovascular, neurological

Gly glycine transaminase oxaluria type 1 renal failure (Gly → oxalate) Ca-oxalate stones

Metabolism of Phe/Tyr

Fig. 39.15

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 Phevarious defects in degradation

neurological, liver failure

Cysteine metabolism

Figs. 39.6 Cys

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