Degradation Heme

heme breakdown

degradation begins inside macrophages of spleen, remove old , damaged (senescent) erythrocytes circulation. in first step, heme converted biliverdin enzyme heme oxygenase (hmox). nadph used reducing agent, molecular oxygen enters reaction, carbon monoxide (co) produced , iron released molecule ferrous ion (fe). co acts cellular messenger , functions in vasodilation.

in addition, heme degradation appears evolutionarily-conserved response oxidative stress. briefly, when cells exposed free radicals, there rapid induction of expression of stress-responsive heme oxygenase-1 (hmox1) isoenzyme catabolizes heme (see below). reason why cells must increase exponentially capability degrade heme in response oxidative stress remains unclear appears part of cytoprotective response avoids deleterious effects of free heme. when large amounts of free heme accumulates, heme detoxification/degradation systems overwhelmed, enabling heme exert damaging effects.

in second reaction, biliverdin converted bilirubin biliverdin reductase (bvr):

bilirubin transported liver facilitated diffusion bound protein (serum albumin), conjugated glucuronic acid become more water-soluble. reaction catalyzed enzyme udp-glucuronosyltransferase.

this form of bilirubin excreted liver in bile. excretion of bilirubin liver biliary canaliculi active, energy dependent , rate limiting process. intestinal bacteria deconjugate bilirubin diglucuronide , convert bilirubin urobilinogens. urobilinogen absorbed intestinal cells , transported kidneys , excreted urine (urobilin, product of oxidation of urobilinogen, responsible yellow colour of urine). remainder travels down digestive tract , converted stercobilinogen. oxidized stercobilin, excreted , responsible color of feces.