| In excess bilirubin imparts a yellow color to the skin. This is called jaundice.
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| Bilirubin is a catabolic product of heme. About 75% is derived from the hemoglobin of senescent red blood cells, which are phagocytosed by mononuclear cells of the spleen, bone marrow, and liver; in normal adults, this contributes a daily load of 250-350 mg of bilirubin. The ring structure of heme is oxidatively cleaved to biliverdin by heme oxygenase, a P450 cytochrome. Biliverdin is, in turn, enzymatically reduced to bilirubin (Fig. 28.4). The normal plasma concentration of bilirubin is less than 17 μmol/L (1.0 mg/dL); however, increased concentrations (more than 50 μmol/L or 3 mg/dL) are readily recognized clinically, because bilirubin imparts a yellow color to the skin (jaundice). Abnormalities in bilirubin metabolism are important pointers in the diagnosis of liver disease.
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| Bilirubin is metabolized by the hepatocytes and excreted by the biliary system
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Whereas biliverdin is water soluble, bilirubin, paradoxically, is not, and so must be further metabolized before excretion (Fig. 28.5). This occurs in the liver, to which bilirubin is transported as a complex with plasma albumin; the hepatic uptake of bilirubin is mediated by a carrier, and this process may be competitively inhibited by other organic anions. The hydrophilicity of bilirubin is increased by esterification of one or both of its carboxylic acid side chains with glucuronic acid, xylose , or ribose. The glucuronide diester is the major conjugate, and its formation is catalyzed by a uridine diphosphate (UDP)-glucuronyl transferase. Conjugated bilirubin is then secreted by the hepatocyte into the biliary canaliculi.
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| Figure 28.3 The pathway of heme synthesis. Part of the pathway is located in the mitochondria and part in the cytosol. ALA, aminolevulinate, PBG, porphobilinogen. Hemoglobin is discussed in Chapter 4. |
| Conjugated bilirubin in the gut is catabolized by bacteria to form stercobilinogen, also known as fecal urobilinogen,
which is a colorless compound. On oxidation, however, stercobilinogen forms stercobilin (otherwise known as fecal urobilin), which is colored; most stercobilin is excreted in the feces, and is responsible for the color of feces. Some stercobilin may be reabsorbed from the gut and, being water soluble, can then be re-excreted by either the liver or the kidneys.
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