Lecture 12

Lecture 12 - Lecture 12 Biliruin synthesis and metabolism...

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Lecture 12 – Biliruin synthesis and metabolism of bilirubin Bilirubin is the degradation product of heme and is colored (in contrast to bile acids) (they are not good for our body -- it needs to leave the body!) Heme is a tetrapyrrole with Fe 2+ complexed in the center. Heme is made in the liver and then exported to tissues via a heme-binding protein (haptoglobin). Heme-containing molecules: Hemoglobin (~70%) Myoglobin Cytochrome P450 - Heme Degradation to Bilirubin o Old red blood cells are taken up by phagocyte the heme is oxidize to bilirubin o Bilirubin will be transfer to blood and binds to albumin Unconjugated bilirubin Unconjugated bilirubin is released into plasma from reticuloendothelial cells which form bilirubin from the breakdown of red blood cells and heme products. Bilirubin is tightly bound to albumin. Hepatic extraction is not very efficient – 20% first pass clearance. The liver only take up 20% of the bilirubin (not like BA) - Bilirubin conjugation o Here is hepatocyte and unconjugate bilirubin in the blood stream and is taken up by OATP2 and exported into the ER and modified to conjugation (UDP- glycuronyl transferase) o Bilrubin can have two glucuronic acid or one the majority has two o Efficient conjugation in the hepatocyte by UDP glucuronyl transferase. o Conjugation greatly increases the aqueous solubility of bilirubin. o Bilirubin mono- and diglucuronides are transported by the canalicular transporter MRP2. o Conjugated bilirubin is able to be filtered by the kidney and excreted in urine . - Bilirubin in the bilitary tract and small intestine o Bilirubin diglucuronide is not absorbed during its transport in the biliary tract Bilirubin enters the bile duct it is not absorbed or altered in the biliary tree Contrast to the BA – o Rate of biliary secretion of bilirubin = rate of formation which is about 300 mg/ day. o At the small intestine, bilirubin diglucuronide similarly remains unaltered. - Bilirubin conversion to urobilinogen o Urobilinogen Colorless compound formed by bacteria in the intestine from bilirubin Can form stercobilin. Intrahepatic Urobilinogen Cycle:
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Lecture 12 - Lecture 12 Biliruin synthesis and metabolism...

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