METABOLISM OF

THE CSKELETONS

Amino Acid Carbon

Skeletons
Amino acids, when deaminated, yield keto acids that, directly or via additional
reactions, feed into major metabolic
pathways (e.g., Krebs Cycle).
Amino acids are grouped into 2 classes,
based on whether or not their carbon
skeletons can be converted to glucose:

glucogenic
ketogenic.

Carbon skeletons of glucogenic amino

acids are degraded to:
pyruvate, or
a 4-C or 5-C intermediate of Krebs Cycle.
These are precursors for gluconeogenesis.

Glucogenic amino acids are the major

carbon source for gluconeogenesis when
glucose levels are low.
They can also be catabolized for energy,
or converted to glycogen or fatty acids for
energy storage.

Carbon skeletons of ketogenic amino acids

are degraded to:

acetyl-CoA, or
acetoacetate.
Acetyl CoA, & its precursor acetoacetate,
cannot yield net production of oxaloacetate,
the gluconeogenesis precursor.

For every 2-C acetyl residue entering Krebs

Cycle, 2 C leave as CO2.
Carbon skeletons of ketogenic amino acids
can be catabolized for energy in Krebs
Cycle, or converted to ketone bodies or
fatty acids.
They cannot be converted to glucose.

OXALOACETATE

ALPHA-KG

ALPHA-KG
PROLINE GLUTAMATE
(OXIDATION)
ARGININE (arginase)
ORNITHINE GLUTAMATE
HISTIDINE (histidase)
UROCANIC ACID Nformimino-glutamate
GLUTAMATE

H2N

H
N

Tetrahydrofolate (THF)

HN
O

pteridine

N
H

CH2
HN

COO

O
C

-aminobenzoate

N
H

C
H

C C COO
H2 H 2

glutamate

Histidine is first converted to glutamate.

The last step in this pathway involves the
cofactor tetrahydrofolate.
Tetrahydrofolate (THF), which has a pteridine
ring, is a reduced form of the B vitamin
folate.

H2N

H
N

H
H

HN

N5
O

HN

H
H

CH2
10N

N5-formimino-THF

N5-formimino-THF is involved in the pathway

for degradation of histidine.
Reactions using THF as donor of a single-C unit
include synthesis of thymidylate, methionine, fmethionine-tRNA, etc.

HC
N

In the pathway of
histidine
degradation,
Nformiminoglutama
te is converted to
glutamate by
transfer of the
formimino group
to THF, yielding
N5-formimino-THF.

CH2
NH

C
H

H
C

COO

NH3+

histidine

NH4+

H2O
H2O
H
C

OOC

HN

CH2

CH2 COO

N-formiminoglutamate

NH

C
H

THF
N 5-formimino-THF

OOC

H
C

CH2

NH3+

CH2 COO

glutamate

PYRUVATE

FUMARATE

The 4-C Krebs Cycle intermediate

succinyl-CoA is produced from
isoleucine, valine, & methionine.
Propionyl-CoA, an intermediate on these
pathways, is also a product of b-oxidation
of fatty acids with an odd number of C
atoms.

H3C
H3C

H2 H2 H
C C C

methionine

COO

NH3+

H2 H2 H
C C C

CH2

NH3+
Adenine

ATP PPi + Pi
H

OH

H
OH

N5-methyl-THF

methylated acceptor
adenosine H2O

H2 H2 H
C C C

homocysteine

S-adenosylmethionine
(SAM)

acceptor

THF

HS

COO

COO

H2 H2
C C

S
CH2

COO

NH3+
Adenine

NH3+

H
C

OH

H
OH

Methionine S-Adenosylmethionine by ATP-

S-adenosylhomocysteine

The branched chain amino acids initially

share in part a common pathway.
Branched Chain a-Keto Acid
Dehydrogenase (BCKDH) is a multisubunit complex homologous to Pyruvate
Dehydrogenase complex.
Genetic deficiency of BCKDH is called
Maple Syrup Urine Disease (MSUD).
High concentrations of branched chain keto
acids in urine give it a characteristic odor.

Transaminase
Phenylalanine
Phenylpyruvate
(Phenylketone)
Phenylalanine Deficient in
Hydroxylase
Phenylketonuria

Genetic
deficiency of
Phenylalanine
Hydroxylase
leads to the
Tyrosine
Melanins
disease
Multiple
phenylketonu
Reactions
ria.
Fumarate + Acetoacetate
Phenylalanine
deamination
via transaminase) accumulate in blood & urine.
&
Mental
retardation results unless treatment begins
phenylpyruvat
immediately
after birth. Treatment consists of limiting
e (the product
phenylalanine intake to levels barely adequate to support
of
growth.
Tyrosine, an essential nutrient for individuals with
phenylalaninemust be supplied in the diet.
phenylketonuria,

Transaminase
Phenylalanine
Phenylpyruvate
(Phenylketone)
Phenylalanine Deficient in
Hydroxylase
Phenylketonuria
Tyrosine

Melanins

Multiple
Reactions
Fumarate + Acetoacetate

Tyrosine is a precursor for synthesis of

melanins and of epinephrine and
norepinephrine.
High [phenylalanine] inhibits Tyrosine
Hydroxylase, on the pathway for synthesis of
the pigment melanin from tyrosine.