Transamination; Urea Cycle; Oxidation of ?-Keto Acids

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Lecture 12

• Transamination Urea Cycle Oxidation of ?-Keto
  Acids

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Catabolism The Big Picture
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Transamination General Reaction (Liver)
O
COO
C
COO
PLP


O
C
COO
COO
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Pyridoxal Phosphate in Transamination
O
H
O
C
HO
O
P
O
O
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?-KG in Transamination
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Transamination
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Why pyridoxal phosphate?
Electron sink that stabilizes intermediate
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PLP General Role in AA Metabolism
Decarboxylases
R
CH
COO
NH
Transaminase
CH

• Forms Schiff base
• Stabilizes intermediates (electron sink)

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Glutamate Dehydrogenase
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Glutamine Transport of Ammonia
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Transport of amino groups
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Disposal of NH4 in Mammals

• NH4 is toxic amino acids are not

Tissues Liver (mitochondria and cytosol)
Transamination pyruvate?alanine ?-KG?glutamate Glu
tamine synthesis Glutamate NH4? Glutamine
Urea
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Urea Cycle Summary
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Synthesis of Carbamoyl Phosphate
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Synthesis of Carbamoyl Phosphate
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Urea Cycle
O
O
C
O
P
O
C
O

O
NH
CH
CH
COOH
COOH
Ornithine
Citrulline
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Urea Cycle-Argininosuccinate synthetase
NH
COOH
O
C
C
CH
COOH
ATP
NH
NH
CH
COOH
AMP
COOH
Aspartate
CH
CH
COOH
COOH
Argininosuccinate
Citrulline
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Urea Cycle-Argininosuccinate Lyase
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Urea Cycle-Arginase
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Regulation of Urea Cycle
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AA Catabolism Via Citric Acid Cycle
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Amino acid degradation

• One of seven metabolic intermediates
• Glucogenic
• Pyruvate
• ?-ketoglutarate
• Succinyl-CoA
• Fumarate
• Oxaloacetate
• Ketogenic (Leucine)
• Acetyl CoA or acetoacetate

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Amino acid degradation

• C3 converted to pyruvate
• C4 converted to oxaloacetate
• C5 converted to a ketoglutarate
• Branched oxidative decarboxylation
• Met, Trp, Phe, and Tyr are precursors for
• cofactors, hormones.

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C3 family is converted to pyruvate
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Glycine degradation
Serine hydroxymethyl transferase

One carbon transfer is important.
Pyruvate
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Tetrahydrofolate and 1-Carbon Transfer
H
N
Glutamate
H
H
O
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HN
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C
CH
COO
O
Pteridine
COO
Can transfer C in several oxidation states
Methyl, methylene, formyl, etc.
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1 Carbon carriers
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Various Oxidation States
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Various Oxidation States
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