Proteins II

Question 1

Where does the urea cycle occur?

Answer 1

mitochondria and cytosol

Question 2

Where does transition in urea cycle from mitochondria to cytosol occur?

Answer 2

Antiporter (ORNT1 and 2) transport ornithine in and citrulline out of mitochondria

Question 3

What does carbomyl phosphate synthetase I do?

Answer 3

mitochondrial enzyme
combines HCO3- with NH3 to form carbomyl phosphate

Key regulated step in urea cycle

enzyme requires N-acetylglutamate for activation

Question 4

What kick starts the urea cycle?

Answer 4

CPS-I (carbomyl phosphate synthetase I)

REQUIRES N-acetylglutamate for activation

Question 5

What is used to transfer ammonia from peripheral tissue

Answer 5

glutamine

• to the kidneys where it is removed in the form of ammonia through urine
• to liver where it is removed in the form of urea (through blood to kidney)

Question 6

What is used to transfer ammonia from muscle

Answer 6

alanine

Question 7

Glutamate dehydrogenase

Answer 7

removes NH3 from glutamate to yield alpha-ketoglutarate and NH3 or vice versa

Liberates NH3 from glutamate or adds NH3 to form glutamate
Ubiquitous in liver/kidney/muscle/periphery

Question 8

What dictates directionality of Glu Dehydrogenase?

Answer 8

relative concentration of Glu, alpha-ketoglu, NH3

Key regulatory point in protein catabolism

Question 9

ATP GTP ADP GDP

Regulation of Glu dehydrogenase?

Answer 9

ATP and GTP are allosteric inhibitors… does this make intuitive sense? If we have lots of energy are we going to be anabolic or catabolic? Anabolic - we are building so we want to inhibit urea cycle

ADP and GDP are allosteric activators… does this make intuitive sense? If we are energy low, we are going to need to breakdown - catabolize –> urea cycle activation :)

Question 10

Why is arginine significant in the urea cycle?

Answer 10

Well, in addition to it being an intermediate (precursor to the production of ornithine and urea via arginase) it can be complexed with glycine to yield creatine phosphate in muscles… which is important for energy

Question 11

In addition to the interconversion of aspartate and oxaloacetate via transamination, aspartate can also be converted to ________ in the urea cycle which can then enter the Krebs cycle and be converted to?

Answer 11

Aspartate–>Fumerate –> Oxaloactate

Question 12

Branched chain amino acids

Answer 12

leucine
isoleucine
Valine

Question 13

MSUD

Answer 13

Genetic deficiency in branched chain alpha-keto acid dehydrogenase

leads to high concentration of branched chain keto acids (as they have already been deaminated) in urine adn gives a characteristic odor

Question 14

TSH

Thyroid stimulating hormone?

Answer 14

stimulates iodide (I-) uptake

stimulates release of T4, T3

Question 15

Thyroid peroxidase

Answer 15

Oxidizes iodide (I-) to I2

Question 16

Thyroglobulin (Tg)

Answer 16

Big ass protein that contains Tyrosine residues that are to iodinated to form T4, T3

Question 17

Thyroxin binding globulin (TBG)

Answer 17

Transports T4 and T3

Question 18

Which form is more active T3 or T4?

Answer 18

T3

Question 19

T3 and T4 are made from which aa

Answer 19

Tyrosine

Question 20

Inherited defects in heme synthesis

Answer 20

Porphyrias

Question 21

gamma-aminolevulinate synthase

gamma-ALA synthase

Answer 21

Enzyme regulating first step of heme production - the smooshing together of Glycine and Succinyl-CoA

also product (gamma-ALA) elevated in urine in tyrosinemia type I?

Question 22

Which micronutrient is involved in heme synthesis?

Answer 22

Zinc

Gamma-ALA dehydratase in zince depedent

Question 23

Lead is known to poison which synthetic pathway?

Answer 23

Lead poisoning –> anemia because it can replace zinc or iron in enzymes involved in heme synthesis

Zn in ALAdyhyratase
Fe in ferrochelatase

Question 24

Heme inhibits? in Heme synthesis

Answer 24

Initial enzymes
ALA-S1
ALA-S2

Question 25

Where does heme synthesis occur?

Answer 25

In mitochondria and cytoplasm

Question 26

Heme degradation?

Answer 26

Heme–>Biliverdin–>Bilirubin–>Bilirubin-diglucuronide–>Stercobilin

Question 27

Bilirubin is transported?

Answer 27

By albumin

Question 28

High bilirubin–?

Answer 28

jaundice

Question 29

Bilirubin is an?

Answer 29

anti-oxidant

Question 30

Crigler Najjar syndrome

Answer 30

Defect in bilirubin glucuronyl-transferase

Question 31

Gilbert syndrome

Answer 31

Defect in bilirubin glucuronyl transferase - less severe

Question 32

Dubin Johnson syndrome

Answer 32

Defect in bilirubin transporter - secrete conjugated bilirubin into bile (to bile, MRP2)

Question 33

What causes neonatal jaundice frequently?

Answer 33

low levels of bilirubin glucuronyl transferase - treat with fluorescent light which converts bilirubin to more polar products allowing removal similar to conjugated bilirubin

Question 34

What are the two nitrogen contributors to the urea cycle?

Answer 34

Aspartate - comes from transamination reaction with Glutamate (AST)

NH4+ directly - comes from glutamate dehydrogenase (ALT generated glutamate from Alanine to yield pyruvate)

Question 35

Tyrptophan metabolism results in the formation of

Answer 35

seratonin, melatonin, niacin