Protein Biochem 2

Question 1

Steps of urea cycle

Answer 1

• occurs in mitochondria and cytosol
• Antiporter ORNT1 (and 2 some) ornithine transported in, citrulline out of mito
  1. ornithine to citrulline by carbamoyl phosphate synthetase I
  2. citrulline +aspartate to argininosuccinate by argininosuccinate synthase
  3. Argininosuccicate to arginine by argininosuccinate lyase
  4. Arginine to ornithine + urea by arginase

Question 2

Carbamoyl phosphate synthetase I

Answer 2

-in mitochondria
-rxn: bicarb +ammonia –> carbamoyl phosphate (uses 2 of 3 ATPs in urea cycle)
Enzyme allosteric activator: N-acetylglutamate
-arginine is an activator of N-acetylglutamate synthase which catalyzes:
acetyl CoA+ glutamate to N-acetylglutamate

-10 mutations found in carbamoyl phosphate synthetase I that can lead to early onset of associated “urea cycle disorder” (with increased ammonia in blood)

Question 3

Transport of ammonia

Answer 3

• ammonia can’t be transported in blood
• Glutamine can “hold” 2 ammonia groups, works for transport (to kidneys, where removed in urine as ammonia; and to liver where it is removed as urea– thru blood to kidney)
• Glutamine synthetase catalyzes glutamate –> glutamine for transport to liver (synthesis uses ATP)
• Glu dehydrogenase = control pt for protein metabolism: controls the direction of either nitrogen removal or incorperation into amino acids

In muscle:
Alanine used instead of glutamine (alanine glucose cycle)
-buildup of pyruvate from glycolysis which can be converted to alanine
-liver can use alanine to convert back to pyruvate and glucose remade can be delivered back to muscle

Kidney removes urea and ammonia

Question 4

Arginine in nerve and muscle function

Answer 4

• NO synthase converts arginine to citrulline to produce NO (vasodilator)
• In urea cycle, arginine –> ornithine by arginase or catalyzed by several enzymes (amidinotransferase, methyltransferase, & kinase) to produce creatine phosphate for energy (muscle)

Question 5

AA breakdown: ketogenic or glucogenic

Answer 5

Ketogenic: no net production of glucose
Glucogenic: produces pyruvate or Kreb cycle intermediates

Question 6

Glucogenic aa

Answer 6

Ala, arg, asn, asp, cys, glu, gln, gly, his, pro, ser, met, thr, val

• Oxaloacetate (4C) from aspartate
• aspartate transamination yields oxaloacetate
• aspartate is converted to fumarate in urea cycle
• fumarate is converted to oxaloacetate in Krebs

Asparagine hydrolyzed by asparaginase yielding aspartate, which can be converted to OAA by transamination
-(enz also anti cancer drug)

Question 7

Ketogenic aa

Answer 7

leucine (leu)
lysine (lys)

-breakdown gives Acetyl-CoA ( acetoacetate)(only 2 C)

Question 8

Ketogenic and glucogenic aa

Answer 8

tyrosine, isoleucine, phenylalanine, tryptophan

tyr, iso, phe, trp

Question 9

Decarboxylation of branched chain aa

Answer 9

• leucine (ketogenic), valine(glucogenic), isoleucine (both)
  1. Deamination by branched-chain aminotransferase to produce alpha keto acids
  2. Decarboxylation by branched-chain alpha keto acid dehydrogenase complex (deficiency? buildup of alpha keto acids in urine: Maple syrup urine disease; could be lethal if not treated)

Question 10

Thyroid chemistry

Answer 10

• tyrosine is used to make T4 (prohormone) that is converted to T3 (hormone) via Deiodinase
• TSH: stimulates iodide (I-) uptake and stimulates release of T4, T3
• Thyroid peroxidase: oxidizes iodide (I-) to I2
• Thyroglobulin (Tg): Contains Tyr residues iodinated by thyroid peroxidase to form T4, T3
• thyroxin binding globulin (TBG): Transports T4, T3

Question 11

Porphyrins

Answer 11

-ex: heme
-cyclic molecules made of 4x pryoles primarily produced in liver
-porphyrins bind Fe2+
Production of porphyrin:
1. Gly + succinyl CoA–> delta-aminolevulinic acid (ALA), cat by delta-aminolevulinate synthase (inhibited by heme/hemin)
2. 2xALA –>porphobilinogen (cat by delta-aminolevulinate dehydratase, which is Zn dependent)
3. Porphobilinogen–»» protoporphyrin IV (cat by 4 enz)
4. Protoporphyrin IX–> heme (cat by Ferrochelatase)

Question 12

Porphyrias

Answer 12

-diseases involving porphyrin synthesis (ie defects in heme synthesis)

Question 13

Lead poisoning

Answer 13

-inhibits delta-aminolevulinic acid dehydratase and ferrochelatase

replaces Zn and Fe respectively

Question 14

Porphyrin (heme) degradation

Answer 14

heme–> biliverdin (green)–> bilirubin (red-orange) –> bilirubin diglucuronide –> urobilinogen–> stercobilin (brown)

Bilirubin (also an anti-ox) transported in blood via albumin
Bilirubin conjugated with glucuronic acid (in liver) to make bilirubin diglucuronide (conjugated bilirubin) via bilirubin glycuronyltransferase
In intestine, bilirubin diglucuronide is oxidized–> stercobilin

Jaundice: when bilirubin cannot be oxidized properly

• can’t break down plethora of heme
• neonatal jaundice: not making bilirubin glucuronyl-transferase yet (treatable with light therapy)

Question 15

2 Nitrogens entering urea cycle

Answer 15

Aspartate
Ammonia

-incorp into urea

Question 16

Glu dehydrogenase

Answer 16

• control pt for protein catabolism
• goes both ways
• ATP, GTP inhibits enz
• ADP, GDP activates enz

Glu dehydrogenase controls how/whether you will get rid of nitrogen in form of glutamine

(alpha ketoglutarate to glutamate via glu dehydrogenase; bi directional)

-Genetic mut in ATP/GTP binding site results in hyperinsulinism- hyperammonemia syndrome: elevated levels of ammonia in blood (gain of func mut)