Amino acid catabolism

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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
- leu, lys         glucogenic are degraded
to pyruvate or a member of the TCA cycle
(succinylCoA, OAA, a-ketoglutarate,
fumarate). In absence of sugars,
glucogenic amino acids permit continued
oxidation of fatty acids by maintaining TCA
cycle intermediates. - ile, phe,
tyr, trp         glucogenic and ketogenic
yield both ketogenic and glucogenic
products. - all others
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• N catabolism
•  
• General strategy
•      removal of N from amino acid by
  transamination (generally
• first or second step of amino acid
  catabolic pathways) and
•         collection of N in glutamic acid
•         deamination of glutamic acid with
  release of NH4
• -glutamate dehydrogenase

3. Collection of N in glutamine or alanine
for delivery to liver
      removal of NH4 by i. secretion or
ii. conversion to urea or other less toxic
form.
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Vitamine B6 family
Pyridoxine
Pyridoxal
Pyridoxamine
Pyridoxal phosphate
See Horton page 212 section 7.7 pyridoxal
phosphate
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Transamination reaction
see text p 537 and fig 17.7.
Lys-protein
NH

a-aminoacid-1
Schiff base with enzyme
R1
H-C-COO-
Lys-protein
NH
Schiff base with substrate
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R1
H-C-COO-
Lys-protein
NH
Schiff base with substrate
Lys-protein
NH2

a-ketoacid-1
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R2
H-C-COO-
Lys-protein
NH
Schiff base with substrate
Lys-protein
NH2

a-keto acid
a-ketoacid-2
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Lys-protein
NH

a-amino acid-2
Schiff base with enzyme
R2
H-C-COO-
Lys-protein
NH
Schiff base with substrate
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Net reaction
a-amino acid-1 a-ketoacid-2
PLP
a-amino acid-2 a-ketoacid-1
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Alanine-glucose cycle
Muscle
glucose
2 pyruvate
2 a-aa
2 a-ka
2 alanine
2 alanine
glucose
Liver
glucose
2 pyruvate
2 Glu
2 a-kG
2 NH4
2 alanine
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• glutamate dehydrogenase (see p 533 for reaction)
• - release or capture of NH4
•         - located in mitochondria
•         - operates near equilibrium

NAD
NADH
glutamate H2O
a-ketoglutarate NH4
NADP
NADPH
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3. transport of N to the liver - glutamine
synthetase - glutaminase - alanine/glucose
cycle
1. Glutamine synthetase
2. Glutaminase
Note glutamate can be used for glucose
synthesis. How?
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MUSCLE
NH4
GluNH2
Pyr
Glu
a-ka
Glucose
a-aa
Ala
a-KG
LIVER
Urea
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Urea cycle
Where Liver mito/cyto Why disposal of
N Immediate source of N glutamate
dehydrogenase glutaminase Fate of urea liver
kidney urine How much 30g urea /
day
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Reactions of urea cycle
1. Carbamyl phosphate synthetase I (mito)
carbamyl phosphate

• committed step
• by NAc glutamate

2. Ornithine transcarbamylase (mito)
Pi
carbamyl phosphate
ornithine
citrulline
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3. Arginosuccinate synthetase (cyto)

AMP PPi
ATP
arginosuccinate
4. Arginosuccinate lyase (cyto)

fumarate
arginine
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5. Arginase (cyto)
urea
ornithine
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NH3
aKG
2ATP
HCO3
2ADP Pi
NADH H
NAD
ornithine
glutamate
asparate
MITO
CYTO
ornithine
citrulline
asparate
glutamate
ATP
AMP PPi
fumarate
See fig 17.26
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