Title: Transamination; Urea Cycle; Oxidation of ?-Keto Acids
1Lecture 12
- Transamination Urea Cycle Oxidation of ?-Keto
Acids
2Catabolism The Big Picture
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4Transamination General Reaction (Liver)
O
COO
C
COO
PLP
O
C
COO
COO
5Pyridoxal Phosphate in Transamination
O
H
O
C
HO
O
P
O
O
6?-KG in Transamination
7Transamination
8Why pyridoxal phosphate?
Electron sink that stabilizes intermediate
9PLP General Role in AA Metabolism
Decarboxylases
R
CH
COO
NH
Transaminase
CH
- Forms Schiff base
- Stabilizes intermediates (electron sink)
10Glutamate Dehydrogenase
11Glutamine Transport of Ammonia
12Transport of amino groups
13Disposal 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
14Urea Cycle Summary
15Synthesis of Carbamoyl Phosphate
16Synthesis of Carbamoyl Phosphate
17Urea Cycle
O
O
C
O
P
O
C
O
O
NH
CH
CH
COOH
COOH
Ornithine
Citrulline
18Urea Cycle-Argininosuccinate synthetase
NH
COOH
O
C
C
CH
COOH
ATP
NH
NH
CH
COOH
AMP
COOH
Aspartate
CH
CH
COOH
COOH
Argininosuccinate
Citrulline
19Urea Cycle-Argininosuccinate Lyase
20Urea Cycle-Arginase
21Regulation of Urea Cycle
22AA Catabolism Via Citric Acid Cycle
23Amino acid degradation
- One of seven metabolic intermediates
- Glucogenic
- Pyruvate
- ?-ketoglutarate
- Succinyl-CoA
- Fumarate
- Oxaloacetate
- Ketogenic (Leucine)
- Acetyl CoA or acetoacetate
24Amino 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.
25C3 family is converted to pyruvate
26Glycine degradation
Serine hydroxymethyl transferase
One carbon transfer is important.
Pyruvate
27Tetrahydrofolate and 1-Carbon Transfer
H
N
Glutamate
H
H
O
5
HN
10
C
CH
COO
O
Pteridine
COO
Can transfer C in several oxidation states
Methyl, methylene, formyl, etc.
281 Carbon carriers
29Various Oxidation States
30Various Oxidation States
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