Nitrogen Metabolism

Question 1

• What is the first step in nitrogen removal?

Answer 1

• Oxidative deamination

Question 2

• What is the rate limiting step in N2 metabolism?

Answer 2

• Converting ammonia to carbamoyl phosphate via carbamoyl phosphate synthetase and NASG

Question 3

• Who is the star of N2 flow in the liver?
• Who is the star of N2 flow in the other tissues?

Answer 3

• Glutamate (liver has a mate)
• Glutamine

Question 4

• What ion are amino acids commonly transported with?

Answer 4

• Na+

Question 5

• Where in the nephron does AA reabsorption occur?

Answer 5

• Proximal convuluted tubule

Question 6

• Hartnup disease is a defect in transport of what type of amino acids?
• What amino acids will you see elevated in urine?
• What is Trp (one of the AAs of Hartnup) a common precursor for?
• What are the symptoms of Hartnup?
• Tx?

Answer 6

• Non-polar or neutral
• Ala, Ser, THr, Val, Leu, Ile, Phe, Tyr, Trp, Gln, Asn, His
• Serotonin, Melatonin, Niacin (precursor for NAD)
• Failure to thrive, nystagmus, photosensitivity
• Tx-niacin repletion and high protein diet (can also do nicotinamide supplementation)

Question 7

• Why is NA (vitamin b3) a good tx for Hartnup?

Answer 7

• Can make NAD without need for de novo pathway using tryptophan

Question 8

• A defect in what type of amino acid transport leads to cytinuria?
• How is the disease inherited?
• What is the common presentation?

Answer 8

• Dibasic
• AR
• Cystine crystals in kidneys, renal colic

COAL stones

Question 9

• What is the biochemical defect in PKU (Classical)?
• What is Phe converted to instead?
• What are the common symptoms?
• How is it treated?

Answer 9

• Phe cannot be converted to Tyr
• Converted to phenypyruvate and phenynllacetate (musty urine odor) and phenylacetate
• Severe impairment of brain function
• Tyr supplementation and dietary limit of Phe

Question 10

• What is the biochemical defect in non-classical PKU?
  *

Answer 10

• Deficiency in THB (Defects in synthesis or regeneration of BH4)
• THB is a cofactor for phenylaline hydroxylase

Question 11

• What are the key diagnosis and treatment plans for a patient with PKU?

Answer 11

• Diagnose before 2 weeks of age
• Levels > 360 umol/L
• Treat with THB (if non-classical)

Question 12

• What enzymatic defect is present in Type I Tyrosinemia?
• What is excreted that is toxic to the liver and kidneys?
• What is their presentation?
• How is it treated?

Answer 12

• Fumarylacetoacetate hydroxylase
• Converts fumarylacetoacetate to fumarate (like the last step in the pathway she gave us)
• Excrete succinylacetone (interferes w/ TCA cycle)
• Renal tubule dysfunction, lack of heme, cabbage like smell
• Liver transplant or Nitisinone (Prevents formation of funarylacetoacetate so it does not have to be broken down)

Question 13

• What enzymatic deficiency is present in type II tyrosinemia?
• What are presenting sx?

Answer 13

• Tyrosine aminotransferase (can’t convert tyrosine to p-hydroxyphenylpyruvate)
• Photophobia, skin lesions

Question 14

• What enzymatic deficiency is present in Type III tyrosinemia?
• What are common presenting sx?

Answer 14

• P-hydroxyphenylpyruvate oxidase
• Intermittent ataxia

Question 15

• What enzymatic deficiency is present in individuals with alkaptonuria?
• Describe key characteristics of the disease

Answer 15

Defect in homogentisate oxidase

AR

Black urine disease

Auto-oxidation of homogensitic acid produces dark pigments in urine and bone

Black pigment in intervertebral discs, degenerative arthritis, onchonosis

Question 16

• Ammonia Toxicity is excessive ammonia d/t disorders in the _ or _ failure and can have highly toxic effects on the CNS
• _ can permeate membranes and cause pH imbalance, swelling of astrocytes-causing _ edema and hypertension
• Can be due to a deficiency in the _ enzyme that converts glutamate to alphaketoglutarate
• Glutamate is essential for the formation of the _ NTX
• Issues with _ cycle of metabolism

Answer 16

• urea cycle, liver
• NH3, cerebral
• glutamate dehydrogenase
• GABA
• TCA

Question 17

• Gout is characterized by high levels of _ in the blood
• Primary hyperuricemia v. Secondary? (which is more common?)
• _ deposits in joints of extremeties and in kidneys
• What kind of diet/population is at risk?
• Tx options?

Answer 17

• Urate/uric acid
• Secondary is more common (secondary is underexcretion of uric acid) and primary is caused by the overproduction of uric acid
• Sodium urate
• Purine rich diet (beans, spinach, meats, alcohol), diabetics, men
• Allopurinol-xanthine oxidase inhibitor OR Colchine-decreases movement of granulocytes to affected areas

Question 18

• Acidemia stimulates the reabsorption of uric acid in the kidney via _ transporter

Answer 18

URAT1

Question 19

• Xanthine oxidase is responsible for what two reactions?
• What would there be a buildup of if allopurinol is used?

Answer 19

• Converting hypoxanthine to xanthine
• Converting xanthine to uric acid
• Hypoxanthine

Question 20

• Hyperammonemia occurs with defects in what three transporters? What else can cause it?
• What is the treatment?

Answer 20

• Mitochondrial ornithine carries, mitochondrial Asp/Glu carrier, dibasic amino acid transporter
• Defects w/ enzymes of the urea cycle
• Tx- limiting protein consumption (and components that conjugate and promote excretion of ammonia)

Question 21

• Most cases of hyperammonemia are inherited in which fashion?
• What is an exeption and how is this inherited?
• What is the common presentation with this case?

Answer 21

• AR
• X linked; Ornithine transcarboxylase enzymatic deficiency hyperammonemia
• Orotic aciduria

Question 22

• What is important about CYTOSOLIC Carbamoyl phosphate synthase II?***
• What stimulates it and what inhibits it?
• What is an intermediate in this pathway?

Answer 22

• First step of de novo pyrimidine synthesis (Does not require NAG)
• PPP, UTP
• Orotic acid

Question 23

• Orotic aciduria from _ deficiencies IS NOT accompanied by hyperammonemia or reduced BUN?

Answer 23

• UMP synthase deficiencies

Question 24

• Reacting plasma with _ reagent in presence or absence of _ will measure _ and _ bilirubin
• Difference between the two will give you _ bilirubin levels
• What is the difference between direct/indirect bilirubin>?

Answer 24

• Diazo, methanol, total, direct
• Indirect
• Direct=conjugated=water soluble
• Indirect=unconjugated=insoluble

Question 25

* Blue light is used to treat _ in newborns by aiding in the _ of bilirubin * Severe jaundice occurs when?

Answer 25

* Jaundice, conjugation * When there is a need to replace the number of red blood cells * Abnormal blood cell chapes * RH incompatability * Cephalohematoma (her son had this so I would know it) * Infection * Enzymatic deficiencies * Premature birth * Hemolytic anemias