protein metabolism I

Question 1

Describe the control points for the urea cycle.

Answer 1

1. glutamate dehydrogenase controlls direction of N removal or incorporation into glutamate. 2. carbamoyl phosphate synthetase 1

Question 2

regulators of glutamate dehydrogenase

Answer 2

1. relative concentrations of Glu, alpha-ketoglutarate and NH3. 2. ATP and GTP are allosteric inhibitors while ADP and GDP are activators

Question 3

how does ornithine get into the mitochondria

Answer 3

ORNT1 (and ORNT2) antiporter- ornithine transported in, citrulline transported out

Question 4

regulators of carbamoyl phosphate synthetase 1

Answer 4

N-acetylglutamate is allosteric activator. Arginine is an activator of N-acetylglutamate synthase which catalyzes Acetyl CoA + glutamate > N-acetylglutamate.

Question 5

List the means of ammonia transport in the blood.

Answer 5

1. Liver: Urea Cycle produces urea for transport
   through blood to kidney. 2. Peripheral Tissue: Gln & Ala produced for transport to Liver. 3. Muscle: Ala produced for transport to Liver whre alanine enters alanine-glucose cycle. 4. Kidney: Removes urea and remove ammonia (from Gln). 1. Liver: Urea Cycle produces urea for transport
   through blood to kidney. 2. Peripheral Tissue: Gln & Ala produced for transport to Liver. 3. Muscle: Ala produced for transport to Liver whre alanine enters alanine-glucose cycle. 4. Kidney: Removes urea and remove ammonia (from Gln).

Question 6

What causes hyperinsulinism-hyperammonemia syndrom

Answer 6

Genetic mutation in ATP/GTP binding site on glutamate dehydrogenase leads to gain of function mutation- elevated levels of ammonia in blood

Question 7

describe cross talk in the urea cycle

Answer 7

arginine can be converted back into citrulline via NO synthase in a rxn that produces nitric oxide OR arginine can be converted into ornithine via arginase OR arginine can be converted into ornithing plus creatine phosphate by amidinotransferase, methyltransferase and kinase

Question 8

glucogenic vs ketogenic aa

Answer 8

Glucogenic: produces pyruvate or Kreb Cycle intermediates, such as OAA which comes from aspartate transamination. Ketogenic: produces no net production of glucose, such as lysine and leucine which produce Acetyl CoA when broken down.

Question 9

why are lysin and leucine ketogenic

Answer 9

They are broken down into Acetyl CoA which enters the Krebs cycle, but both carbons are removed as CO2, thus there is nothing left for production of glucose

Question 10

Why is oxaloacetate a glucogenic aa

Answer 10

aspartate is converted to OAA via AST. Aspartate is also converted to fumarate in urea cycle which is then converted to OAA in krebs cycle.

Question 11

Function of asparaginase

Answer 11

Converts asparagine to aspartate. Can be used as an anti-cancer drug to deprive cells of asn

Question 12

list branched chain amino acids

Answer 12

leucine, valine and isoleucine

Question 13

describe decarboxylation of BCAAs

Answer 13

BCAAs are deaminated by branched chain amin aminotransferases into alpha-ketoacids. Then they are decarboxylated by branched chain alpha-ketoacid dehydrogenase complex to form acyl CoA derivatives

Question 14

Maple syrup urin disease

Answer 14

occurs when the branched chain alpha ketoacid dehydrogenase complex is deficient and there is consequently a build up of the a-keto acids in urine (“sweet smelling”). Can be lethal if not treated

Question 15

What aa is thyroid hormone produced from

Answer 15

Tyrosine > T4 (prohormone) > T3 (hormone via deiodinase)

Question 16

How does TSH work

Answer 16

TSH stimulates iodide uptake and stimulates release of T4, T3

Question 17

How are T3 and T4 transported from thyroid through blood

Answer 17

thyroxin binding globulin

Question 18

steps in thyroid synthesis

Answer 18

TSH stimulates iodide uptake > Thyroid peroxidase oxidizes idodide (I-) to iodine (I2) > thyroglobulin enters cell and 2-5 tyrosines are iodinated to form T4, T3 > thyroid binding globulin transports T3, T4 from cell

Question 19

porphyria

Answer 19

inherited defect in heme (porphyrin) synthesis

Question 20

structure of porphyrins

Answer 20

Such as heme- cyclic molecules made of 4X pyroles primarily produced in liver. They bind Fe2+ iron

Question 21

Porphyrin production

Answer 21

glycine + succinyl CoA > d-aminolevulinic acid (d-aminolevulinate synthase) > d-ALA transferred from mitochondria to cytosol > prophobilinogen (d-aminolevulinate dehydratase) > protoporphyrin IX(mitochondria) > heme (ferrochelatase)

Question 22

Which enzymes does lead inhibit

Answer 22

(d-Aminolevulinate dehydratase, ferrochelatase) ”lead poisining”.

Question 23

list steps in prophyrin degradation

Answer 23

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

Question 24

how is bilirubin transported in blood

Answer 24

via albumin

Question 25

Neonatal jaundice- cause and treatment

Answer 25

bilirubin diglucuronide is not produced fast enough by low levels of bilirubin glycuronyltransferase. Treated with fluorescent light which converts bilirubin to more polar products which can be removed

Question 26

List disorders of bilirubin glucuronyl transferase

Answer 26

Crigler-Najjar syndrome and gilbert syndrome

Question 27

List disorders of bilirubin transport

Answer 27

Dubin Johnson syndrome