BCH 3120 Lecture Notes - Lecture 16: Keto Acid, Deamination, Transamination
March 1, 2017
Amino Acid Catabolism
Amino Acid Metabolism
Amino acid will be broken down into NH3 and the carbon skeleton
-Deamination: NH3 will be eliminated from the aa
•NH3 will be detoxified and eliminated through the urea cycle - will usually be converted to urea and then
excreted
-Carbon skeleton can be converted into multiple things:
•Glucogenic metabolites: converted into pyruvate to produce glucose
•Ketogenic: acetyl-CoA and ketone bodies
Deamination
Transamination must occur first: NH3 will be transferred
-Catalyzed by aminotrasferase
-Converts amino acids into α-keto acids
-NH3 will be transferred to α-ketoglutarate, converting it into glutamate and creating an α-keto acid
-Occurs in the cytoplasm
1
March 1, 2017
-
-NB: can occur will all aa’s except for proline
-NB: requires PLP co-factor
•PLP reacts with the aa to form PLP-aa imine
•PLP will then act as an electron sink to allow for deprotonation, converting the C-N single bond of the aa into a
double bond
-There will also be reprotonation at a different C
•The imine will then undergo hydrolysis to form the α-keto acid and PMP
•αKG then reacts in the reverse direction with PMP to make glutamate and PLP
Glutamate can be converted back into α-ketoglutarate by glutamate dehydrogenase
-
-Allosterically controlled:
•Inhibited by GTP and NADH
-When GTP and NADH are high, there is abundant energy and there is no need to degrade glutamate
•Activated by ADP and NAD+
-Need to make more ATP
-Increases αKG increases TCA flux
-Glutamate formation tends to be preferred
-Occurs in the mitochondria
-Exergonic
-Can use NAD+ or NADP+
-Also releases NH4+, which will be excreted - mediated by the urea cycle
2
March 1, 2017
Urea Cycle
Urea: contains 2 N - one from free NH3 and one from aspartate
-Aspartate will be converted to fumarate
-Fumarate can be converted into oxaloacetate
Needs 3 ATP: will produce 2 ADP and 1 AMP
-4 ATP equivalents because PPi will be further hydrolyzed into 2 Pi
Details of the Urea Cycle
3