1. Figures: Lehninger-4ed; chapter: 18 Stryer-5ed; chapter: 23
Amino acid metabolism III. Brake down of amino acids, glucoplastic and ketoplastic amino acids
Figures:
Lehninger-4ed; chapter: 18
Stryer-5ed; chapter: 23

2. Overview of amino acid catabolism in mammals

4. Summary of amino acid catabolism: fates of the carbon chain

5. 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)

6. Mixed amino acids (both ketogenic and glucogenic):
• tryptophan (Trp)
• phenylalanine (Phe)
• tyrosine (Tyr)
• threonine (Thr)
• isoleucine (Ile)

7. 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)

8. Conversion of one-carbon units in tetrahydrofolate

9. 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!

10. 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!

11. Minor pathway in humans:
10-30% of Thr catabolism

12. Oxidative cleavage pathway
(the 2 C-atoms from Gly
do not enter the citric acid
cycle!!!)

13. 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!

15. Try and Phe are precursors for biologically active molecules!

16. 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

17. (Urea cycle)
Allosteric activator: ADP
Allosteric inhibitor: GTP

19. The primary pathway for Thr
degradation in humans!

20. • 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!)

21. • 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)