Amino Acid Metabolism

Question 1

Amino Acid Degradation

Answer 1

• we cannot store excess aa so they must be degraded
• degraded as fuel or biosynthetic intermediates
• a-amino group removed and most nitrogen excreted as urea
• carbon skeletons broken down into TCA cycle intermediates

Question 2

Fate of Carbon Skeletons

Answer 2

Glucogenic: converted to glucose
- OA, pyruvate, a-KG, fumarate, succinyl-CoA
- converted to glucose via gluconeogenesis
Ketogenic: converted to acetyl CoA
- ketone bodies
- 7 intermediates can be formed from all 20 aa

Question 3

Transamination

Answer 3

Removal of a-amino group

• transfer of amino group of a-keto acid
• catalysed by aminotransferases (transaminases)
• uses pyruvate phosphate as a cofactor
• collect amino groups from all 20 aa to form glutamate

A-amino acid 1 + a-keto acid 2 = a-keto acid 2 + a-amino acid 2
A-amino acid 1 + a-keto glutarate = a-keto acid 2 + glutamate

Question 4

Aspartate Aminotraferase

Answer 4

aspartate + a-keto glutarate = OA + glutamate

Question 5

Alanine Aminotransferase

Answer 5

alanine + a-keto glutarate = pyruvate + glutamate

Question 6

Removal of a-amino group from glutamate

Answer 6

Glutamate Dehydrogenase reaction

• oxidative deamination
• glutamate forms Schiff base intermediate (oxidation)
• hydrolysis of ammonia forms a-keto glutarate

Question 7

Urea Cycle

Answer 7

• cytosol and matrix
  1. ammonia combine with bicarbonate to form caramoyl phosphate
  2. transfer of carbamoyl group
  3. condensation with aspartate
  4. cleavage of fumarate
  5. hydrolysis releasing urea
• product: ornithine that can recombine with the carbamoyl group of carbamoyl phosphate

Question 8

Net Reaction of Urea Cycle

Answer 8

CO2 + NH3 + 3ATP + aspartate + 2H20 = urea + 2 ADP + 2 Pi + AMP + PPi + fumarate

Question 9

Carbamoyl Phosphate Formation

Answer 9

1. bicarbonate phosphorylated
   - reacts with ATP to give carbonyl phosphate
2. ammonia attacks carbonyl gorup of carbonyl phosphate to form carbamate
3. phosphorylate carbamate activated donor of carbamoyl group
   - final product is carbamoyl phosphate
   - uses 2 ATP

Question 10

Link of TCA and Urea Cycles

Answer 10

Arginino succinate formed from citrulline and aspartate and can be converted to arginine in the urea cycle and fumarate that goes into the TCA cycle
- OA converted into aspartate using glutamate and asp-aminotransferase

Question 11

Nitrogen Metabolism

Answer 11

• role of glutamine: don’t wanna excrete all nitrogen as some is needed for synthesis of nucleotides, aa, etc
• some ammonium incorporated into glutamine that is a nitrogen donor
• glutamine synthase

Question 12

Pyridoxal Phosphate Structure

Answer 12

• slightly basic pyridine ring attached to a slightly acidic hydroxyl group
• can form stable tautomer in which pyridine nitrogen is protonated and positively charged
• aldehyde group forms covalent Schiff base intermediates with lysine and amino acid substrate
• protonated PLP is an electron sink stabilizing carbanions
• selective cleavage of carbon bond: bond being broken must be perpendicular to the pi orbitals of the electron sink (stereoelectronic control)