Simmons III Flashcards
What does HGPRTase do?
- Takes purine base and combines with PRPP to make IMP or GMP
- Converts back to nucleotide
What is Lesch Nyhan syndrome?
- deficient HGPRTase
- Compulsive aggressiveness and self mutilation leading children to eat their own lips
What is gout?
- Accumulation of Na urate crystals in joints and uric acid stones in kidney
- Hyperuricemia & Hyperuricosuria can cause
Why do less women get gout?
Estrogen enhances uric acid excretion
Gout treatment?
- 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
What is ALA?
Aminolevulinic acid - product in first rate limiting step of heme synthesis by combination of Glycine and Succinyl CoA
What is Porphyrias?
Diseases that derive from defects heme production pathway
Usually effect NS or skin
What are Porphyrinogens?
- Compounds that have no double bond at bridging carbons & are colorless
- Light can non enzymatically oxidized Porphyrinogens into Porphyrins
What is Acute intermittent porphyria?
- 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
Treatment of Acute intermittent porphyria?
Glucose infusion to increase insulin which lowers ALA synthase
As such diets can worsen symptoms as lower insulin
Heme infusion to provide negative feedback
What is variegate porphyria?
- 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
What do you need to stay out of light for?
Variegate porphyria
What does liver do to bilirubin?
Conjugates it making it more soluble
What is heme degraded into?
Iron & bilirubin
What is globin broken into?
Free AAs
How does bilirubin become exreted in feces?
Bacterial in LI deconjugate bilirubin so it can be excreted in feces
What is Hyperbilirubinemia?
- 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
Signs of biliary obstruction?
- 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
What happens in infantile biliubemia?
- 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
