Transcript Amino acid metabolism III. Brake down of amino acids

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
This Me group is about 1,000 times more
reactive than the Me group from N5-Me-tetrahydrofolate!
The only other known reaction in which triphosphate is displaced from ATP
occurs in the synthesis of coenzyme B12!
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 the
N5-methyl form!
Minor pathway in humans:
10-30% of Thr catabolism
Oxidative cleavage pathway
(the 2 C-atoms from Gly
do not enter the citric acid
cycle!!!)
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 an
oxygen atom of O2 and reduction of the other oxygen atom to H2O
(Urea cycle)
Allosteric activator: ADP
Allosteric inhibitor: GTP
The primary pathway for Thr
degradation 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 reactions
five cofactors: thiamine pyrophosphate
FAD
NAD
lipoate
coenzyme A
inactive enzyme complex = phosphorylated form!
(when the dietary intake of branched-chain amino acids is low)