Catabolism of the Carbon Skeletons of Amino Acids Twenty amino acid carbon skeletons are funneled into only seven mols. Several enzyme cofactors play important roles in amino acid metabolism. Ten amino acids are degraded to Acetyl- CoA. The dehyrdation of tryptophan is the most complex pathway.
Transcript
1. Catabolism of the Carbon Skeletons of Amino Acids Twenty
amino acid carbon skeletons are funneled into only seven mols.
Several enzyme cofactors play important roles in amino acid
metabolism. Ten amino acids are degraded to Acetyl-CoA. The
dehyrdation of tryptophan is the most complex pathway.
2. Ketogenic amino acids aas that are degraded to Acetyl CoA or
acetoacetyl CoA Leu Lys Glucogenic amino acids aas that are
degraded to pyruvate, -KG, succinyl CoA, fumarate, or OAA 14 aas
Both ketogenic and glucogenic amino acids (PITT) Phe Ile Tyr
Trp
3. Catabolism of the carbon skeletons of amino acidsThe C
skeletons of 20 amino acids arefunneled into only 7 molecules:
Pyruvate Acetyl CoA Acetoacetyl CoA -Ketoglutarate Succinyl CoA
Fumarate Oxaloacetate
4. Important factors in amino acid metabolism 1-Carbon transfer
is a common type of reaction in amino acid metabolism. CO2 Biotin
1-C transfer tetrahydrofolate -CH3 S-Adenosylmethionine
5. Pyruvate is the point of entry for Ala, Ser, Cys, Thr and
Trp
6. Catabolicpathway forAsp and Asn
7. Met requires SAM Met is converted to succinyl CoA in 9
steps. S-adenosylmethionine (SAM), formed along this pathway, is an
important molecule for transferring methyl groups!
8. Trp as precursor
9. CatabolicPathways forIle, Leu, Val(not in theliver)
10. Branched amino acids are not degraded in liver Leu, Ile,Val
are primarily oxidized to their corresponding - ketoacids in
extrahepatic tissues like muscle, adipose, kidney, and brain
tissue. Branched chain aminotransferase is specific to these
tissues.
11. Branched amino acids share the same enzymes for the first 2
reactions Leu Acetyl CoA Ile Acetyl CoA Val Succinyl CoA
12. 2nd enzyme -ketoacid dehydrogenasecomplex may be
defectiveThis causes Maple syrup disease Mental retardation Infant
deaths Burnt maple syrup odor in the body and urine of the patient
The levels of -ketoacids and the branched chain amino acids are
high!!
13. Screeningtest forMSUD
14. Oxygenases are required for thedegradation of aromatic
amino acids Molecular oxygen is used to break an aromatic ring. The
degradation of Phe starts with hydroxylation. Enzyme: Phe
hydroxylase This enzyme is called monooxygenase (or mixed- function
oxygenase) because one atom of O2 appears in the product (tyr) and
the other in H2O The reductant is tetrahydrobiopterin(made in the
body, not a vitamin)
15. Inborn errors The catabolism of Phe is very important also.
Enzyme defects in Phe catabolism lead to several genetic
diseases.
16. Diseases related with Phe catabolism Phenylketonuira (PKU)
Phenylalanine hydroxylase Alkaptonuria homogentisate
1,2-dioxygenase Tyrosinemia II tyrosine amino transferase
Tyrosineamia I -hydroxyphenylpyruvate dioxygenase
17. Degradation ofPhe and Tyr
18. alkaptonuria In 1902, Archibald Garrod described this
disease. Large amounts of homogentisate excreted in the urine.
Zacutus Lusinatus, in 1646, wrote about a patient who passed black
urine: none of the predicted evils ensued, he married, began a
large family, and lived a long healthy life, always passing urine
as ink!!
19. PKU Elevated levels of Phe in blood due to the deficiency
of Phe hydroxylase Autosomal recessive Impaired brain development,
mental retardation Treatment: diet low in Phe