Simmons III

Question 1

What does HGPRTase do?

Answer 1

• Takes purine base and combines with PRPP to make IMP or GMP
• Converts back to nucleotide

Question 2

What is Lesch Nyhan syndrome?

Answer 2

• deficient HGPRTase

- Compulsive aggressiveness and self mutilation leading children to eat their own lips

Question 3

What is gout?

Answer 3

• Accumulation of Na urate crystals in joints and uric acid stones in kidney
• Hyperuricemia & Hyperuricosuria can cause

Question 4

Why do less women get gout?

Answer 4

Estrogen enhances uric acid excretion

Question 5

Gout treatment?

Answer 5

• Anti Inflammatories such as NSAIDS
• Colchicine - slows movement of granulocytes
• Uricosuric drugs - enhances uric acid excretion
• Allopurinol - inhibits xanthine oxidase to stop formation of uric acid

Question 6

What is ALA?

Answer 6

Aminolevulinic acid - product in first rate limiting step of heme synthesis by combination of Glycine and Succinyl CoA

Question 7

What is Porphyrias?

Answer 7

Diseases that derive from defects heme production pathway

Usually effect NS or skin

Question 8

What are Porphyrinogens?

Answer 8

• Compounds that have no double bond at bridging carbons & are colorless
• Light can non enzymatically oxidized Porphyrinogens into Porphyrins

Question 9

What is Acute intermittent porphyria?

Answer 9

• Deficient porphobilinogen deaminase
• Need to have at least 50% deficiency
• ALA and porphobilinogen increase in body and are toxic to neurons
• As heme is negative feedback, heme production does not drop as no negative feedback
• Causes nerve damages leading to acute pain, tachycardia, hypertension etc

Question 10

Treatment of Acute intermittent porphyria?

Answer 10

Glucose infusion to increase insulin which lowers ALA synthase
As such diets can worsen symptoms as lower insulin
Heme infusion to provide negative feedback

Question 11

What is variegate porphyria?

Answer 11

• Defect in protoporphyrinogen oxidase
• Heme production does not drop much
• Back up of more intermediates
• Intermediates are porphyrinogens which can be converted to porphyrins in skin by light and porphyrics and be converted to 1 O 2 by light which can destroy tissue
• Causes neural damage and skin lesions
• Patients need to stay out of light

Question 12

What do you need to stay out of light for?

Answer 12

Variegate porphyria

Question 13

What does liver do to bilirubin?

Answer 13

Conjugates it making it more soluble

Question 14

What is heme degraded into?

Answer 14

Iron & bilirubin

Question 15

What is globin broken into?

Answer 15

Free AAs

Question 16

How does bilirubin become exreted in feces?

Answer 16

Bacterial in LI deconjugate bilirubin so it can be excreted in feces

Question 17

What is Hyperbilirubinemia?

Answer 17

• Causes jaundice changing skin color
• Above 1 mg/dl but signs show at 2
• Conjugated bilirubinemia is benign - just shows you something is wrong
• Unconjugated bilirubinemia is benign up to 25mg/dl at which point it overcomes albumins ability to bind it
  Can cause encephalopathy causing retardation and seizures

Question 18

Signs of biliary obstruction?

Answer 18

• conjugated bilirubin as it has already made to liver

- Dark urine as it is in blood, white feces as rubin cant make it to LI

Question 19

What happens in infantile biliubemia?

Answer 19

• Newborns have fragile blood cells leading to hemolysis
  Immature liver that is not good at conjugating this lysed RBC so it appears in blood
• Blue light is absorbed by unconjugated bilirubin turning it into a soluble isomer which will not get into brain and can be more easily excreted