Porphyins, Heme, Bile Flashcards
Where are porphyrins found?
Myoglobin
Hemoglobin
Cytochrome C
How is delta-aminolevalinate synthesized?
Succinyl-CoA + glycine
What enzyme catalyzes synthesis of delta-aminolevalinate?
Aminolevulinic acid synthase (ALAS)
What does ALAS need as a coenzyme?
Pyridoxal phosphate (PLP) vitamin B6
How is porphobilinogen created?
2 aminolevalinate
What enzyme catalyzes porphobilinogen synthesis?
Aminolevulinic acid dehydratase (ALAD)
What can vitamin B6 deficiency cause?
Anemia
What is protoporphyrin?
Heme B without Fe2+
What are two isoforms of ALAS?
ALAS 1: all cells (x-linked)
ALAS 2: liver bone marrow
What is hemin?
Heme with Fe3+ (oxidized form)
What does increase hemin level indicate?
Too much heme A, B and C
What does too much hemin cause?
Inhibition of ALAS enzyme
What do heavy metals inhibit?
ALAD
What does decreased ALAD cause?
Accumulation of ALA
What is ALAD deficiency called?
Doss porphyria
ALAD porphyria
What do you treat doss porphyria?
Prophylactic hemin to slow ALAS and decrease porphyrin accumulation
What is heme broken down into?
Biliverdin + Fe3+
How does bilirubin get transported in the blood?
Albumin
Biliverdin is broken down to bilirubin by what?
Biliverdin reductase
What happens to bilirubin in the liver?
It is glycosylated to bilirubin diglucoronide
What is indirect and direct bilirubin?
Indirect (unconjugated): not glycosylated
Direct (conjugated): glycosylated
What enzyme conjugates bilirubin to glucose?
Uridine diphosphogluconurate glucuronosyltransferase (UDP-Glucuronosyltransferase)
What is Gilbert’s syndrome?
Decreased UDP-glucuronosyltransferase
What does Gilbert’s syndrome cause?
Increased indirect and decreased direct bilirubin and increased bilirubin in the blood (jaundice)
What does CO act as?
A vasodilator helping blood flow in tissue injury caused by heme oxidase
What is the most important antioxidant in the body?
Bilirubin
What is elevated in a liver deficiency or blocked bile duct?
Alkaline phosphatase (ALP)
What are the two primary bile salts/acids?
Cholic acid
Chenodeoxycholic acid
How are primary bile salts turned to secondary bile salts?
Removal of a hydroxyl group by bacteria
How are secondary bile salts made more soluble?
Liver adds a taurine or glycine
What activates transcription of HMG-CoA reductase?
SREBP
When does HMG-CoA reductase get activated?
When cholesterol is low
What inhibits transcription of 7alpha-hydroxylase gene when cholesterol is low?
SREBP
Why does SREBP inhibit 7alpha-hydroxylase gene?
To not waste cholesterol on bile production
What stimulates transcription of 7alpha-hydroxylase gene when cholesterol is too high?
Liver X receptor (lowers cholesterol by increasing bile acids)
What inhibits transcription of the 7alpha-hydroxylase gene when bile acid levels are too high?
Farnesoid X receptor (bile acids are too high)
Most important enzyme in classical pathway:
Cholesterol 7alpha-Hydroxylase
Most important enzyme in acidic pathway:
Sterol 27-Hydroxylase
