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.
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
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
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
Pyruvate is the point of entry for Ala, Ser, Cys, Thr and Trp
CatabolicPathways forIle, Leu, Val(not in theliver)
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.
Branched amino acids share the same enzymes for the first 2 reactions Leu Acetyl CoA Ile Acetyl CoA Val Succinyl CoA
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!!
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)
Inborn errors The catabolism of Phe is very important also. Enzyme defects in Phe catabolism lead to several genetic diseases.
Diseases related with Phe catabolism Phenylketonuira (PKU) Phenylalanine hydroxylase Alkaptonuria homogentisate 1,2-dioxygenase Tyrosinemia II tyrosine amino transferase Tyrosineamia I -hydroxyphenylpyruvate dioxygenase
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!!”
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