BILIRUBIN (CONJUGATED AND UNCONJUGATED)


Bilirubin is the end product of the catabolism of heme, derived principally from circulating hemoglobin.

METABOLISM OF BILIRUBIN
The first step in the degradation of the heme group to bilirubin is the cleavage of its α – methane bridge to form biliverdin, a linear tetrapyrrole. This reaction is catalysed by heme oxygenase. Two aspects of this reaction are noteworthy. First, this enzyme is a monooxygenase; O2 and NADPH are required for the cleavage reaction. Second, a methane – bridge carbon is released as carbon monoxide (Stryer,2000). This endogenous production of CO pose a special problem in the evolution of  oxygen carriers (Katzung, 1998).
The central methane bridge of biliverdin is then reduced by biliverdin reductase to form bilirubin.

Bilirubin is transported in the plasma bound tightly to plasma-albumin in the ratio of 1:1 above which dissociation occurs. In pathological conditions that affect the liver, concentration of free bilirubin known as unconjugated or indirect reacting bilirubin increases. Once in the liver, unconjugated bilirubin which is largely water –insoluble is converted to the water soluble (direct –reacting) conjugated bilirubin, which is easily excreted into the bile from where it gets into the gastro-intestinal tract (Katzung, 1998).With in the guts, some bilirubin is excreted with feaces as stercobilirubin and gives colour to faeces. A fraction is hydrolysed back to unconjugated bilirubin and reabsorbed into plasma through enterohepatic circulation.

Why do mammals reduce biliverdin to bilirubin? Resent studies, stryer (2000), have shown that bilirubin is a very effective antioxidant,where as biliverdin is not. In scavenging two hydroperoxy radicals, bilirubin is oxidized to biliverdin which is then rapidly reduced to again form bilirubin. On a molar bases, bilirubin bound to albumin is about a tenth as effective as ascorbate (vitamin C) in affording protection against water – soluble peroxides (Stryer,2000). Bilirubin, urate and ascorbate are the three principal antioxidants in plasma. In membranes, bilirubin is a highly potent antioxidant, rivaling vitamin E in this regard. These studies suggest that the end product of a degradative pathway maybe selected in evolution to exert a beneficial action (Stryer,2000).
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