Module 4

Question 1

Urea cycle occurs in which two places

mitochondria
cytosol
cytoplasm
ECM

Answer 1

mito and cytoplasm

Question 2

5 enzymes of the urea cycle

which 2 need ATP

Answer 2

CPS1 - carbomyl phosphate (2 ATP)
OTC - ornithine trans-carbonmylase 
ASS - argino-succinate synthetase (1 ATP) 
ASL - argino-succinase lyase
A - arginase

Question 3

AA —-> transamination —-> a-keto acid (which will be used in all metabolic intermediates for energy)

what molecule is involved in this process - ultimately leading to glutamate?

Answer 3

a-KG

Question 4

PLP enzyme - what does it do?

what are the 2 products of the reaction it’s in charge of?

Answer 4

COFACTOR: active Vit B6 - carbon and oxygen molecule swapping

alanine (AA) + a-KG (keto acid) —–AAT——> pyruvate + glutamate

AAT - alanine aminotransaminase (second reaction when the molecule is being broken down further (aspartate); the enzyme is ASPARTATE AT

Question 5

glutamate DH - converts a-KG to?

Answer 5

glutamate

Question 6

IN MUSCLE

glutamate + ATP + NH4 —> ______ + ADP

what enzyme?

Answer 6

glutamine

glutamine synthetase

Question 7

IN LIVER - OXIDATIVE DEAMINATION

glutamine –> NH4 + glutamate via - which enzyme?

glutamate (now inside the liver) —> a-KG + NH4 - which enzyme? thus releasing what?

Answer 7

glutaminase

glutamate DH - releasing that ammonia

Question 8

__ ATP per aspartate = _ATP/nitrogen

Answer 8

4

2

Question 9

Which one of these activates CPS1?

arginine
glutamate semialdehyde
ornithinine
n-acetyl-glutamate

Answer 9

N-A Glutamate (sole purpose in life to activate CPS1)

Question 10

Hemodialysis

Answer 10

means of decreasing ammonia in body and blood

Question 11

Folic acid is key to what?

Answer 11

nucleotides - prevent neural tube defects

Question 12

N5, N10 - METHLENE-TETRAHYDROFOLATE

wtf is this?

Answer 12

active form of folate

Question 13

Cystathionine synthase - related to what condition?

Answer 13

homocystinuria

homocystine build up (cannot make cystine)

Question 14

Phenylalanine hydroxylase and dihydrobiopterin reductase - related to what condition?

Answer 14

phenylketonuria

Question 15

Phenylalanine hydroxylase also associated with what other AA’s catabolism?

Answer 15

tyrosine

Question 16

polyphenol oxidase added to urine of patients with this condition - leading to black urine

Answer 16

alcaptonuria - related to melanin

Question 17

Uric acid is formed from the breakdown of pyrimidines or purines?

Answer 17

purines

Question 18

T or F: glutamate has no role in NT

Answer 18

F

Question 19

When the body is infected - positive or negative N balance?

Answer 19

-ve

Question 20

2 purine bases

3 pyrimidine bases

Answer 20

adenine - guanine

uracil, thymine, cytosine

Question 21

What happens if you cannot methylate uracil?

Answer 21

death - cannot replicate DNA

Question 22

Ribose + 5-P + ATP –> AMP + _______? via what enzyme?

Answer 22

PRPP

PRPP synthetase

Question 23

de novo purine synthesis

what is the key controlling enyzme?

Answer 23

glutamine phosphoribosyl amidotransfrase

Question 24

When making _MP = ATP is the energy source and glutamine is the nitrogen donor

When making _MP = GTP is the energy source and aspartic acid is the nitrogen donor

ATP Cost
Costs __ GTP to form AMP
Costs __ ATP to form GMP

Answer 24

GMP
AMP

1
2

Question 25

What enzyme aids in the production of deoxyribonucleotide (removes hydroxyl group from hte sugar)

Answer 25

ribonucleotide reductase

Question 26

____ will shut the enzyme down, a nucleotide will encourage other deoxyribonucleotides to be produced

Answer 26

dATP

Question 27

Purine Metabolism (Diseases) SCID (Severe Combined Immunodeficiency) - what enzyme is dysfunctional?

Answer 27

SCID (Severe Combined Immunodeficiency) o Adenosine deaminase is nonfunctional o Can’t remove amino group from adenosine and convert adenosine to inosine o Deoxyadenosine and derivatives build up o Loss of immune function – No T and B cells o Cells can’t divide because we can’t replicate DNA

Question 28

Purine Metabolism (Diseases) Lesch-Nyan Syndrome - what enzyme is dysfunctional?

Answer 28

``` • Lesch-Nyan Syndrome o Hypoxanthine guanine phosphoribosyltransferase is nonfunctional o Increased levels of PRPP o Decreased levels of GMP and IMP o Increased de novo purine synthesis o Purines and uric acid build up o Potential for gout o Mental retardation o Self mutilation ```

Question 29

Purine Metabolism (Diseases) Primary Gout - what enzyme is dysfunctional?

Answer 29

Primary Gout o PRPP insensitive to feedback control o HGPRT reduced (salvage pathway) o Uric acid build up o Pain in the joints - Often times severe pain in the big toe o It often happens after a person has been partying – rich meals with lots of protein (DNA) and they go to bed and get this terrible pain in the middle of the night in their big toe o

Question 30

Purine Metabolism (Diseases) Von Gierke’s Disease - what enzyme is dysfunctional?

Answer 30

Von Gierke’s Disease § Glucose 6 phosphatase and the transporter protein that allows G6P to enter the ER are not functioning § G6P builds up, encouraging the hexose monophosphate shunt which gives ribose 5 phosphate § Build up of Ribose 5P that leads to an excess of PRPP, which can override the controls for purine synthesis and produce more IMP and GTP than necessary § The resultant nucleotides are not needed so they must be degraded which increases uric acid

Question 31

Purine Metabolism (Diseases) Secondary gout - what enzyme is dysfunctional?

Answer 31

• Secondary Gout o Diet and lifestyle play a role o The kidney is not able to excrete uric acid as sufficiently as it should o Initially it can give pain in the big toe o Pain is so severe that the individual cannot sleep o Genetic propensity for a build-up of uric acid o If someone is overweight, circulation is not as good as it used to be o Alcohol has a negative effect o Can lead to dehydration o Decrease in excretion of uric acid by the kidney o Caviar can lead to increased risk of gout o Gout attack can occur as they are lying down o King’s were susceptible o Lots of good food without any physical activity o Kidney disease can also have an effect on gout o Lifestyle changes are the best way to deal with gout o Pharmaceuticals can be used o Can also occur as a result of: o Leukemia o Chemotherapy o Multiple myeloma o Lead poisoning o Kidney disease

Question 32

Tx for 2ndary gout = allopurinol; blocks what enzyme

Answer 32

xanthene oxidase

Question 33

T or F: folic acid is not involved in pyrimidine base

Answer 33

T

Question 34

T or F: carbamoylphospate synthetase I is one of the enzymes involved in pyrimidine formation

Answer 34

F - this is solely related to urea synthesis

Question 35

Build up of urea in the blood?

Answer 35

kidney failure

Question 36

build up of ammonia in the blood

Answer 36

liver failure