Nitrogen Metabolism

Question 1

first step of nitrogen removal and enzyme involved

Answer 1

oxidative deamination via glutamate dehydrogenase

Question 2

key player in AA metabolism

Answer 2

glutamate

Question 3

source of carbon skeletons for urea cycle generated from transamination reactions

Answer 3

aspartate

Question 4

nitrogen sources for the urea cycle

Answer 4

Glu/Gln

Question 5

inborn errors of AA resorption (2)

Answer 5

hartnup - nonpolar AA

Cystinuria - dibasic AA

Question 6

AA are resorbed in which portion of the nephron

Answer 6

proximal convoluted tubule

Question 7

cystinuria is characterized by defective ________ enzyme in what tissue

Answer 7

shared dibasic-cystine transporter in the proximal renal tubule and JEJUNAL MUCOSA

Question 8

what picks up the slack for the shared dibasic-cystine transporter in the small intestines?

Answer 8

a peptide transporter

Question 9

hartnup is characterized by a defective ________ enzyme in what tissue

Answer 9

neutral AA transporter in the proximal renal tubule and jejunal mucosa

Question 10

most important AA that is ineffectively resorbed in the PCT in patients with hartnup is

Answer 10

tryptophan, precursor for neurotransmitters

Question 11

dibasic AA

Answer 11

COAL
Cystine 
Ornithine 
Argnine 
Lysine

Question 12

neutral AA transporter deficiency

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

Answer 12

hartnup disease

Question 13

Trp is the precursor for what molecules

Answer 13

serotonin
melatonin
niacin (which is a precursor for NAD) - note niacin deficiency

Question 14

manifestations of Hartnup disease

Answer 14

failure to thrive, nystagmus, intermittent ataxia, tremor and photosensitivity
pellagra like dermatosis
attacks triggered by sunlight, drugs, physical stress

Question 15

treatment for hartnup

Answer 15

nicotinic acid

niacin repletion and high protein diet, daily nicotinamide supplementation

Question 16

nitroprusside test indicates

Answer 16

cystinuria

Question 17

cystinuria can dissolve kidney stones by changing their diet to be more

Answer 17

alkalinic

Question 18

phenylketonuria is caused by deficient

Answer 18

Phenylalanine hydroxylase (PAH) 
most common IEM

Question 19

PKU symptoms can be limited by

Answer 19

dietary limitation of Phe and supplementation of Tyr

Question 20

secondary PKU is characterized by

Answer 20

Tetrahydrobiopterin deficiency
THB is a key coenzyme in phenylalanine hydroxylase
defect in synthesis/regeneration of B4

Question 21

PKU babies must be treated before _____ of age
Dietary restrictions begin if blood Phe levels are greater than _____
some patients with milder forms can increase their metabolic control with supplementation with _______

Answer 21

2 weeks of age
6mg/dL
improved metabolic control when treated with THB

Question 22

Tetrahydriobiopterin is a cofactor for what enzyme

Answer 22

phenylalanine hydroxylase

Question 23

synthetic THB treats what IEM

Answer 23

secondary PKU

Question 24

tyrosinemias are characterized by

Answer 24

elevated blood levels of tyrosine

Question 25

deficient fumarylacetoacetate hydrolase results in what form of tyrosinemia and what does the enzyme do

Answer 25

Type I | converts tyrosime to fumarate

Question 26

type I tyrosinemia is characterized by deficient

Answer 26

fumarylacetoacetate hydrolase

Question 27

Type I tyrosinemia babies have a _____ like smell and excrete ______, which is toxic to liver and kidneys, interferes with the TCA cycle, causes renal tubule dysfunction and inhibits biosynthesis of heme

Answer 27

cabbage | secrete succinylacetone

Question 28

type II tyrosinemia is characterized by

Answer 28

defective tyrosine aminotransferase | results in photophobia/skin lesions

Question 29

type III tyrosinemia is characterized by

Answer 29

defective p-hydroxyphenylpyruvate oxidase and results in intermittent ataxia

Question 30

what type of tyrosinemia is most common and used to require a liver transplant?

Answer 30

type I deficient fumarylacetoacetate hydrolase buildup of succinylacetone

Question 31

defective homogentisate oxidase, an enzyme in tyrosine degradation pathway, results in black urine and bones is termed

Answer 31

alkaptonuria

Question 32

a buildup of homogentistic acid is due to what enzyme in alkaptonuria

Answer 32

homogentisate oxidase

Question 33

NH3 toxicity MoA

Answer 33

permeates membranes | pH imbalance, swelling of astrocytes in the brain --> cerebral edema/intracranial hypertension

Question 34

enzyme that catalyzes the oxidative deamination of glutamate to alpha-ketoglutarate

Answer 34

glutamate dehydrogenase

Question 35

ammonia depletes what NT

Answer 35

glutamate

Question 36

gout is a buildup of

Answer 36

uric acid in the blood and deposition of sodium urate crystals primary hyperuricemia --> overproduction of uric acid Secondary hyperuricemia --> underexcretion of uric acid

Question 37

diets rich in ________ along with what other foods/drinks trigger gout

Answer 37

purines | alcohol, meat, seafood

Question 38

treatments of gout

Answer 38

colchicine decreases the movement of granulocytes to the affected areas use of allopurinol inhibits xanthine oxidase

Question 39

hyperammonemia is caused by defects in what enzymes

Answer 39

six enzymes of the urea cycle or 3 specific transporters | mitochondrial ornithine carriers, mitochondrial Asp/Glu carrier, dibasic AA transporter

Question 40

more severe cases of hyperammonemia are due to defects in what enzymes

Answer 40

3 specific transporters | mitochondrial ornithine carriers, mitochondrial Asp/Glu carrier, dibasic AA transporter

Question 41

ornithine transcarbamoylase deficiency results in what condition

Answer 41

hyperammonemia defects cause excess carbamoyl phosphate which can spill out into cytoplasm metabolized by pyrimidine synthesis pathway to orotic acid then accumulates/excreted in the urine (orotic aciduria) --> decreases BUN

Question 42

first step of de novo pyrimidine synthesis is mediated by what enzyme

Answer 42

carbamoyl phosphate synthetase II - cytosol | unique from mitochondrial isoform

Question 43

carbamoyl phosphate synthetase I

Answer 43

urea cycle mitochondrial NAG activated

Question 44

Carbomyl phosphate synthetase II

Answer 44

pyrimidine synthesis cytosolic PRPP activated

Question 45

Carbamoyl phosphate synthetase I is the rate limiting step for what process

Answer 45

urea cycle deficiency == hyperammonemia creates carbamoyl phosphate which is used added to ornithine to make citrulline (allows urea to exit the mitochondria)

Question 46

bilirubin is conjugated with

Answer 46

glucuronic acid | by UDP glucuronyl transferase

Question 47

unconjugated bilirubin is trasnported to the liver from the spleen using

Answer 47

albumin?

Question 48

heme is broken down to bilirubin in the

Answer 48

macrophage

Question 49

unconjugated bilirubin is water ______ while conjugated bilirubin is water _______

Answer 49

insoluble | soluble

Question 50

jaundice is common in newborns because

Answer 50

placenta handles removal of bilirubin, after birth babies liver must take over the job