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, a-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 acids
The C skeletons of 20 amino acids are
funneled into only 7 molecules:
– Pyruvate
– Acetyl CoA
– Acetoacetyl CoA
– a-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.
Catabolic
pathway for
Asp 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.
Catabolic
Pathways for
Ile, Leu, Val
(not in the
liver)

10.
Branched amino acids are not
degraded in liver
 Leu, Ile,Val are primarily oxidized to
their corresponding a- 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 a-ketoacid dehydrogenase
complex may be defective
This causes “Maple syrup disease”
 Mental retardation
 Infant deaths
 Burnt maple syrup odor in the body
and urine of the patient
 The levels of a-ketoacids and the
branched chain amino acids are high!!

13.
Screening test
for MSUD

14.
Oxygenases are required for the
degradation 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 of
Phe 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

20.
Alternative
Pathway for Phe
degradation in
PKU