amino acid metabolism iii. brake down of amino acids, glucoplastic and ketoplastic amino acids...
TRANSCRIPT
Amino acid metabolism III. Brake down of amino acids, glucoplastic
and ketoplastic amino acids
Figures:
Lehninger-4ed; chapter: 18
Stryer-5ed; chapter: 23
Overview of amino acid catabolism in mammals
Summary of amino acid catabolism: fates of the carbon chain
Purely ketogenic amino acids: can yield ketone bodies in the liver• leucine (Leu) very common in proteins• lysine (Lys)
Glucogenic amino acids: can be converted to glucose and glycogen • alanine (Ala) • cysteine (Cys) • glycine (Gly) • serine (Ser) • asparagine (Asn) • aspartate (Asp) • methionine (Met) • valine (Val) • arginine (Arg) • glutamine (Gln) • glutamate (Glu) • histidine (His) • proline (Pro)
Mixed amino acids (both ketogenic and glucogenic): • tryptophan (Trp) • phenylalanine (Phe) • tyrosine (Tyr) • threonine (Thr) • isoleucine (Ile)
Enzyme cofactors in amino acid catabolism
These cofactors transfer one-carbon groups in different oxidation states:• Biotin (most oxidized: COO–)• Tetrahydrofolate (intermediate ox. state: methylene, methenyl,
formyl, formimino groups, and sometimes methyl)• S-Adenosylmethionine (most reduced: methyl)
Conversion of one-carbon units in tetrahydrofolate
The preferred cofactor for biological methyl group transfer: adoMet
The only other known reaction in which triphosphate is displaced from ATPoccurs in the synthesis of coenzyme B12!
This Me group is about 1,000 times morereactive than the Me group from N5-Me-tetrahydrofolate!
Coenzyme B12-dependent reactions in mammals:• methionine synthase reaction
• rearrangament of L-methylmalonyl-CoA to succinyl-CoA
Vitamin B12 deficiency disease: metabolic folates become trapped in theN5-methyl form!
Minor pathway in humans:10-30% of Thr catabolism
Oxidative cleavage pathway(the 2 C-atoms from Glydo not enter the citric acidcycle!!!)
Another pathway of Gly degradation:
D-amino acid oxidase:• is present at high levels in the kidney• has as primary function the detoxification of ingested D-amino acids
Calcium oxalate: 75% of kidney stones!
Try and Phe are precursors for biologically active molecules!
The first step in Phe degradation requires the cofactor tetrahydrobiopterin:
(mixed function oxidase)
Mixed function oxidases: catalyze simultaneous hydroxylation of a substrate by anoxygen atom of O2 and reduction of the other oxygen atom to H2O
(Urea cycle)
Allosteric activator: ADPAllosteric inhibitor: GTP
The primary pathway for Thrdegradation in humans!
• much of the catabolism of amino acids takes place in the liver• branched-chain amino acids are oxidized as fuels primarily in the muscles, adipose, kidney, and brain tissue
(absent in the liver!)
• branched-chain -keto acid dehydrogenase complex
• pyruvate dehydrogenase complex
• -ketoglutarate dehydrogenase complex
similar structure, same reaction mechanism
catalyze homologous reactionsfive cofactors: thiamine pyrophosphate
FADNADlipoatecoenzyme A
inactive enzyme complex = phosphorylated form!(when the dietary intake of branched-chain amino acids is low)