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Amino acids catabolism usually begins by the removal of the amino group through:-Transamination - oxidative deamination
Amino group is then dispose as urea. Carbon skeleton produced from standard amino acids are then degraded to form seven metabolic product :- acetyl-CoA - acetoacetyl-CoA - pyruvate - a-ketoglutarate - succinyl CoA - fumarate - oxaloacetate
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Those amino acids that can be converted to acetyl-CoA and acetoacetyl-CoA are referred to as KETOGENIC because they can be converted to either fatty acids or ketone bodies.
Those aa than can be degraded to pyruvate, a-ketoglutarate, succinyl-CoA , fumarate and oxaloacetate, are referred to as GLUCOGENIC they can be used in gluconeogenesis. All amino acids except lysine and leucine are at least partly glucogenic. Lys and leu are purely ketogenic. Amino acid that yield acetyl-CoA can be divided into 2 groups:i) Those that yield pyruvate as intermediate ii) Those not involves pyruvate as intermediate Group (i) includes Ala, Cys, Gly, Ser, and Thr. (ACGST) Group (ii) includes Phe, Lys, Leu, Trp, and Tyr. (FKLWY)
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NH3
NH3
NH3
UREA CYCLE
In the matrix of mitochondria of hepatocytes 1. HCO3- + +NH4
carbamoyl phosphate synthase
2ATP
2ADP + Pi + 3H+
Bicarbonate react with ammonium ion to form carbamoyl O phosphate. 2ATP are used- one to activate the II NH C bicarbonate, another to phosphorylate the carbamate, 2 - H The reaction is irreversible.
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O
II
O
II I
NH2 C O -P OO-
Ornithine transcarbamyolase
Pi
Carbamoyl phosphate react with ornithine to form citrulline. Citrulline is then transported to the cytoplasm.
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In the cytosol
H O I II + H3N C C I CH2 I CH2 I CH citrulline I 2 N H I C O I NH2 H O I II + H3N C C OO I CH2 ATP I CH 2 H O AMP + PPi I I II COO CH H3N+ C C OI I 2 I N H CH2 CH2 I I + I C NH - CH C=O I I INH 2 COOO aspartate argininosuccinate synthase argininosuccinate
H O argininosuccinate lyase I II + H3N C C O I CH2 I COOCH2 I I COO CH CH2 I I II N H CH2 CH I I I C NH - CH COOI I NH2 fumarate COOargininosuccinate
arginase
Arginase catalysed the hydrolysis of arginine to form ornithine and urea. Note: Three ATPs is consumed in the synthesis of one molecule of urea.
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malate
a-keto acid
Aspartate argininosuccinate cycle temporarily shut down the citric acid cycle to allow the conversion of oxaloacetate to aspartate
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a-amino-b-ketobutyrate
CoASH a-amino-b-ketobutyrate lyase Acetyl CoA
Threonine
NADH + H+
NAD+
N5, N10 methylene THF
H2O
+
glycine
cysteine
THF CoASH
a-amino-b-ketobutyrate
NAD+
NH4
cysteine sulfate
transamination desulfuration NAD+
serine
Ser. dehydratase
+
pyruvate
CO2
Alanine
Acetyl-CoA
The catabolic pathway of Thr, Gly, Ser, Ala, and Cys to acetyl-CoA with pyruvate as intermediate
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Tryptophan
NH3-CH-COOI CH2 I
Phenylalanine
Tyrosine
alanine
Leucine
Lysine
formate
+
fumarate
a-ketoadipate
Acetoacetate
Acetoacetyl-CoA
Acetyl-CoA
Catabolic pathway of Trp, Phe, Tyr, Leu, and Lys to acetyl-CoA (pyruvate is not an intermediate)
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Glutamate-g-semialdehyde
Histidine
Glutamate
glutamine
a-ketoglutarate
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Propionyl-CoA
Methylmalonyl-CoA
Succinyl-CoA
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Aspartate
Oxalaoacetate
Tyr acetoacetate
Phe Cys
Ala
Thr
Trp
Acetoacetyl-CoA a-ketoadipate Trp Lys Asp oxaloacetate malate Asn fumarate citrate Acetyl-CoA
Arg
Pro
Krebs cycle
Glutamate -g-semialdehyde
glu
His
Val 22
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