Nitrogen Metabolism

Question 1

The first step in nitrogen metabolism is:

Via which enzyme:

Answer 1

Oxidative deamination via glutamate dehydrogenase

Question 2

Urea cycle

Answer 2

Asp + citrulline –> arginosuccinate –> fumarate (goes to TCA) + Arg –> urea and ornithine (+carbamoyl phosphate) –> citrulline

Question 3

What is the carbon skeleton source for urea cycle reactions?

Answer 3

Aspartate

Question 4

What cannot be resorbed in Hartnup’s?

In cystinuria?

Answer 4

Nonpolar AAs

Dibasic AAs

Question 5

Why is Hartnup’s and Cystinuria a “double whammy” in a sense?

Answer 5

There is poor absorption in both the intestines and malabsorption.

Question 6

Where does reabsorption of AA and Glc occur?

Answer 6

In the PCT

Question 7

What gene/protein function in reuptake of Glc and AA?

Answer 7

SLC

Question 8

Hartnup’s Disease has poor absorption which AAs?

Answer 8

Nonpolar

Ala, Ser, Thr, Val, Leu, Ile, Phe, Tyr, Trp, Gln, Asn and His

Question 9

How does HD manifest? (5)

Answer 9

Infancy to thrive as an infant
Nystagmus
Ataxia
Photosensitivity
Pellegra

Question 10

What is the treatment for HD generally? (3)

Answer 10

Niacin w/ a high protein diet and nicotinamide supplementation.

Question 11

Trp pathway

Answer 11

Trp –> niacin –> NAD+/NADP+

Trp –> 5-hydroxytrptophan –> serotonin –> melatonin

Question 12

How does niacin help in HD?

Answer 12

The de novo pathway does not work due to malabsorption of Trp.
Therefore, Niacin can convert to NAD+/NADP+

Question 13

What are “dibasic” AAs? (4)

Answer 13

COAL
Cys
Orn
Arg
Lys

Question 14

What doe patients present with in cystinuria? (2)

Answer 14

Renal crystals

Renal colic

Question 15

Draw the Phe to Fumarate pathway

Answer 15

Phe –> Tyr –> p-Hydroxyphenylpyruvate –> homogentisate –> Maleylacetoacetate –> Fumarylacetoacetate –> Fumarate

Question 16

Type II tyrosinemia occurs from:

Enzyme

Answer 16

From Tyr –> p-Hydroxyphenylpyruvate

tyrosine aminotransferase

Question 17

Type III tyrosinemia occurs from:

Enzyme

Answer 17

p-Hydroxyphenylpyruvate –> Homogentisate

p-hydroxypyruvate oxidase

Question 18

Alkaptonuria occurs from:

Enzyme

Answer 18

Homogentisate –> Maleylacetoacetate

homogentisate oxidase

Question 19

Type I tyrosinemia occurs from:

Enzyme

Answer 19

Fumarylacetoacetate –> fumarate

fumarylacetoacetate hydrolase

Question 20

PKU is a defect in which enzyme?

Answer 20

PAH

Phenylalanine hydroxylase

Question 21

Instead of being metabolized normally to Tyr, what happens to Phe in PKU?

Answer 21

Phe –> phenylpyruvate –> phenylacetate

Question 22

PKU disrupts what physiologically?

Answer 22

Neurotransmission and blocks AA transport in the brain.

Question 23

Secondary PKU results from:

Answer 23

BH4 deficiency (a cofactor of PAH).

Question 24

What test tests for PKU?

Answer 24

Guthrie test

Question 25

PKU must be found when? What levels of blood Phe are concerning? Treatment of PKU

Answer 25

Before 2 wks >360 umol/L BH4

Question 26

Tyrosinemia

Answer 26

Increased Tyr in the blood.

Question 27

Which tyrosinemia is most common and what is teh treatment?

Answer 27

Type I | Liver transplant

Question 28

Alkaptonuria

Answer 28

AKA black urine disease Caused by accumulation of homogentisate Noted also by black pigmentation in the IV disks Auto recessive

Question 29

Which AA must be supplemented in a patient with PKU?

Answer 29

Tyr

Question 30

Ammonia toxicity

Answer 30

Excessive NH3 | Causes pH imbalance, swelling in the brain

Question 31

Ammonia can cause a depletion of what?

Answer 31

Glutamate, an NT in the brain

Question 32

Gout

Answer 32

Build up of uric acid in the joints due to diets rich in purnies.

Question 33

Treatment of gout

Answer 33

Colchicine, which decreases movement of granulocytes to the affected area. Allopurinol, which inhibits xanthine oxidase

Question 34

Altered uric acid excretion can come from (3):

Answer 34

Poor glomerular filtration, decreased tubular secretion or enhanced tubular resorption.

Question 35

Purine rich foods (6):

Answer 35

Beans, spinach, lentils, alcohol, meat and seafood.

Question 36

Hyperammonemia

Answer 36

Occurs in defects in any of the 6 enzymes in the urea cycle or with 3 transporters.

Question 37

Carbamoyl phosphate synthetase II function

Answer 37

First step in de novo synthesis of pyrimidines

Question 38

CPSaseI isoform chart (3)

Answer 38

Urea cycle Mitochondrial NAG-activated

Question 39

CPSaseII isoform chart (3)

Answer 39

Pyrimidine synthesis Cytosolic PRPP-activated

Question 40

Conjugated (direct) vs. unconjugated (indirect) bilirubin

Answer 40

Conjugated is soluble | Unconjugated is not soluble

Question 41

Jaundice in newborns is due to:

Answer 41

Build up of unconjugated bilirubin as the baby's liver is not matured enough to process. Should return to normal 7-10 days after delivery

Question 42

Physiological jaundice

Answer 42

Jaundice due to adult pathology - sickle cell, liver diseae, anemias, etc.