Amino acid metabolism

Nitrogen balance
Dietary protein
amino acid pool
protein
synthesis
N excretion
(NH4+. urea)
catabolism,
biosynthesis
normal N balance: N ingested = N excreted
negative N balance: N ingested < N excreted
positive N balance: N ingested > N excreted

excess dietary amino acids (in excess over that required for
protein synthesis) are not stored but are degraded and
carbon skeletons used for glucose biosynthesis or energy
production.

proteins are constantly turning over and must therefore be
constantly replaced by protein synthesis. This requires a
steady supply of all 20 amino acids.

Protein sparing: if carbohydrate or fat intake is inadequate,
some dietary protein will be used for energy production,
reducing availability of amino acids for protein synthesis.
As carbohydrate and fats in diet increase, need for dietary
protein decreases.

Kwashiorkor: adequate caloric intake, but inadequate
protein intake.
Amino acid catabolism

accounts for ~ 10% of energy requirement of adults

When:

excess protein in diet

protein degradation exceeds demand for new protein

starvation when carbohydrates are not available

protein storing seeds such as beans, peas, etc.

Glucogenic vs ketogenic amino acids
 ketogenic: yield AcCoA or AcAc as end products of
catabolism
 glucogenic: are degraded to pyruvate or a member of
the TCA cycle (succinylCoA, OAA, -ketoglutarate,
fumarate). In absence of sugars, glucogenic amino
acids permit continued oxidation of fatty acids by
maintaining TCA cycle intermediates.
 glucogenic and ketogenic: yield both ketogenic and
glucogenic products.
 ile, phe, tyr and trp are glucogenic. leu and lys are
ketogenic. All others are glucogenic.
N catabolism
general strategy:
 removal of N from amino acid by transamination
(generally first or second step of amino acid catabolic
pathways)
 collection of N in glutamic acid
 deamination of glutamic acid with release of NH4+
 Removal of NH4+ by : i. secretion; or ii. conversion to
urea or other less toxic form.
i and ii. Transamination; see text p 537 and fig 17.7. see also
section 7.7, p212 on pyridoxal phosphate.
iii. glutamate dehydrogenase (see p 533 for reaction)
 located in mitochondria
 operates near equilibrium
iv. removal of NH4+
 in liver by urea cycle and formation of urea
 in other tissues collection of N in glutamine or alanine
for transport to liver
 formation of glutamine -glutamine synthetase (see
fig 17.4)
 glutamine transported to liver or kidney
where it is broken down to glutamate and
NH4+ by glutaminase.
 in kidney NH4+ is secreted in urine with an
anion such as -OH butyrate.
+
 in liver NH4 is used to make urea.
 formation of alanine - "alanine glucose cycle"
 in skeletal muscle pyruvate acts as acceptor
in transaminase reaction. Ala is transported
to the liver where it undergoes
transamination to yield pyruvate that is used
for gluconeogenesis. The glucose is released
and can return to muscle where is
glycolytically degraded back to pyruvate.
 N metabolism in kidney
 glutamine converted to glutamate + NH4+ by
glutaminase and NH4+ is secreted in urine
along with an anion.
 during acidosis glutamine is shunted from
liver to kidney to conserve bicarbonate in
the liver (ie less NH4+ used for synthesis of
urea) and extra NH4+ production in kidney


is secreted with anions (eg ketone bodies) in
urine.
-ketoglutarate produced in kidney is used
for production of HCO3-, which is released
to blood (see p 563) and glucose.
Urea cycle
 occurs in liver mito and cyto
 urea secreted in urine - up to 30 g/day
 source of N - glutamate dehydrogenase, glutaminase
 Reactions of:
 carbamylphosphate synthase - mito
 produces carbamyl phosphate from 2
ATP, CO2 and NH4+
 committed step
 activated by N'Ac glutamate
 ornithine transcarbamylase - mito
 tightly coupled to carbamylphosphate
synthase so that carbamyl phosphate is
rapidly added to ornithine to form
citrulline
 arginosuccinate synthtase - cyto
 aspartate transported into mito in
exchange for glu.
 arginosuccinate lyase - cyto
 yields arginine and fumarate.
 fumarate used for synthesis of glucose
(fumarate
malate OAA PEP
etc.
 arginase - cyto
 yields urea and ornithine
 ornithine transported back into mito
 absent from kidney which cannot make
urea but is a source of arginine.
Interorgan relationships in N metabolism
Epithelial cells
of intestine
Several
steps
Glu’NH2
cittruline
Glu’NH2
Liver
Kidney
cittruline
Arg
Arginine
Arginine
Several
steps
Urea
Urea
cycle
Ornithine
Several
steps
creatine
glutamate
To urine
Muscle
creatine
P-creatine
creatinine
non-enzymatic
Adapted from Devlin,
Biochemistry with Clinical Corrleation
4th ed.
Alanine - glucose cycle
Muscle
glucose
2 pyruvate
-aa
-ka
2 alanine
glucose
2 alanine
Liver
glucose
2 alanine
-ka
2 pyruvate
-aa