09 Urea Cycle

Question 1

How is excess nitrogen handled?

Answer 1

Urea Cycle

Question 2

What is the urea cycle part of?

Answer 2

Energy production, regulation of glucose levels, fatty acid biosynthesis, ketone body synthesis

Question 3

Pyridoxal phosphate is a key cofactor in

Answer 3

amino acid metabolism

Question 4

What are two PLP dependent transamination reactions

Answer 4

1. aspartate + PLP to oxaloacetate +PMP
2. alpha-ketoglutarate + PMP glutamate + PLP
   PING PONG

Question 5

transaminases are

Answer 5

an important assay for tissue damage

Question 6

Alanine Transaminase

Answer 6

ALT or GOT (glutamate-oxaloacetate transaminase)

Question 7

Heart and Liver damage

Answer 7

appear in serum after heart attack, drug toxicity, or infection-leak from injured cells

Question 8

PLP acts as a what sink

Answer 8

electron

Question 9

How are amino groups collected and transported to the liver for excretion?

Answer 9

1. transaminases- funnels the amino groups to glutamate. There’s a lot of dif transaminase
2. Glutamine Synthase- key regulator of cellular nitrogen metabolism
3. Glutamine - transports amino groups from extrahepatic tissues to liver

Question 10

What’s the glucose alanine cycle?

Answer 10

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

Question 11

How is ammonium ion generated?

Answer 11

It’s generated from the oxidative deamination of glutamate in the liver

Question 12

What does GDH stand for?

Answer 12

Glutamate dehydrogenase- a mitochondrial enzyme

Question 13

What form are the amino acids collected in, in the liver?

Answer 13

form of glutamate

Question 14

How is GDH is activated?

Answer 14

ADP and NAD+, low energy

Question 15

How is GDH inhibited?

Answer 15

It’s inhibited GTP and NADH, high energy

Question 16

How is urea cycle regulated?

Answer 16

Allosteric activation of carbamoyl-phosphate-synthase-I by N-acetylgluatmate

Question 17

degradation of proteins and amino acids: oxidation of the carbon skeleton

Answer 17

The coidation of the carbon skeleton is a critical role of vitamin B6 (PLP) in amino acid metabolism.

Question 18

Oxidation of the carbon skeleton occurs when

Answer 18

• Normal protein synthesis & degradation (Leftover AA)
• Diet rich in protein (AA are not stored)
• Starvation or uncontolled diabetes

Question 19

What are the two classifications of amino acids?

Answer 19

glucogenic (glucose) or ketogenic (fats or ketone bodies)

Question 20

Urea Cycle and TCA Cycles can be linked: what can happen to fumarate?

Answer 20

converted to malate and metabolized in cytosol or transported into mitochondria

Question 21

Urea Cycle and TCA cycles can be linked: who is the nitrogen donor

Answer 21

Asp ormed from OAA & Glu

Question 22

Humans can synthesized 10/20 common amino acids.

Answer 22

Nonessential: Alanine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Serine, Proline, Tyrosine

Question 23

Building blocks for synthesis of non essential amino acids come from…

Answer 23

glycolysis and the TCA

Question 24

What are the classes of PLP catalyzed reactions, three classes

Answer 24

Transamination Reaction -Amino acid synthesis and breakdown
Decarboxylation Reactions - Synthesis of of neurotransmitters
Beta and y-elimination/replacement- amino acid synthesis

Question 25

Stereo-electronic control of PLP reactions

Answer 25

sigma bond to be cleaved is orientated with pi orbitals

Question 26

Synthesis of an essential amino acid

Answer 26

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

Question 27

Another example of substrate channeling: Carbamoyl Phosphate Synthase (E. Coli)

Answer 27

• 96 A tunnel
• prevents loss of intermediates
• protects unstable intermediates from rapid breakdown
• increases local concentration of NH3

Question 28

An example of carbamoyl phosphate synthase

Answer 28

One example is in mammals:

• Enzymes of the urea cycle channel substrates
• only urea is released into the general pool of metabolites