09 Urea Cycle Flashcards
How is excess nitrogen handled?
Urea Cycle
What is the urea cycle part of?
Energy production, regulation of glucose levels, fatty acid biosynthesis, ketone body synthesis
Pyridoxal phosphate is a key cofactor in
amino acid metabolism
What are two PLP dependent transamination reactions
- aspartate + PLP to oxaloacetate +PMP
- alpha-ketoglutarate + PMP glutamate + PLP
PING PONG
transaminases are
an important assay for tissue damage
Alanine Transaminase
ALT or GOT (glutamate-oxaloacetate transaminase)
Heart and Liver damage
appear in serum after heart attack, drug toxicity, or infection-leak from injured cells
PLP acts as a what sink
electron
How are amino groups collected and transported to the liver for excretion?
- transaminases- funnels the amino groups to glutamate. There’s a lot of dif transaminase
- Glutamine Synthase- key regulator of cellular nitrogen metabolism
- Glutamine - transports amino groups from extrahepatic tissues to liver
What’s the glucose alanine cycle?
alanine transports ammonia from active skeletal muscle to liver.
- contracted muscles produce pyruvate from glucose
- lactate and pyruvate are produced from glycolysis and ammonia from breakdown of amino acids
- products must go to the liver where ammonia is excreted and pyruvate and lactate is converted to glucose
How is ammonium ion generated?
It’s generated from the oxidative deamination of glutamate in the liver
What does GDH stand for?
Glutamate dehydrogenase- a mitochondrial enzyme
What form are the amino acids collected in, in the liver?
form of glutamate
How is GDH is activated?
ADP and NAD+, low energy
How is GDH inhibited?
It’s inhibited GTP and NADH, high energy
How is urea cycle regulated?
Allosteric activation of carbamoyl-phosphate-synthase-I by N-acetylgluatmate
degradation of proteins and amino acids: oxidation of the carbon skeleton
The coidation of the carbon skeleton is a critical role of vitamin B6 (PLP) in amino acid metabolism.
Oxidation of the carbon skeleton occurs when
- Normal protein synthesis & degradation (Leftover AA)
- Diet rich in protein (AA are not stored)
- Starvation or uncontolled diabetes
What are the two classifications of amino acids?
glucogenic (glucose) or ketogenic (fats or ketone bodies)
Urea Cycle and TCA Cycles can be linked: what can happen to fumarate?
converted to malate and metabolized in cytosol or transported into mitochondria
Urea Cycle and TCA cycles can be linked: who is the nitrogen donor
Asp ormed from OAA & Glu
Humans can synthesized 10/20 common amino acids.
Nonessential: Alanine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Serine, Proline, Tyrosine
Building blocks for synthesis of non essential amino acids come from…
glycolysis and the TCA
What are the classes of PLP catalyzed reactions, three classes
Transamination Reaction -Amino acid synthesis and breakdown
Decarboxylation Reactions - Synthesis of of neurotransmitters
Beta and y-elimination/replacement- amino acid synthesis
Stereo-electronic control of PLP reactions
sigma bond to be cleaved is orientated with pi orbitals
Synthesis of an essential amino acid
Tryptophan Synthase alpha beta complex from salmonella.
alpha and beta sites are ~25 A apart
Alpha and beta sites are connected by 25~30A tunnel substrate channeling
Another example of substrate channeling: Carbamoyl Phosphate Synthase (E. Coli)
- 96 A tunnel
- prevents loss of intermediates
- protects unstable intermediates from rapid breakdown
- increases local concentration of NH3
An example of carbamoyl phosphate synthase
One example is in mammals:
- Enzymes of the urea cycle channel substrates
- only urea is released into the general pool of metabolites
