Bilirubin, biosynthesis

Knowledge of the biochemistry of the porphyrins and of heme is basic to understanding the varied functions of hemoproteins (see below) in the body. The porphyrias are a group of diseases caused by abnormalities in the pathway of biosynthesis of the various porphyrins. Although porphyrias are not very prevalent, physicians must be aware of them. A much more prevalent clinical condition is jaundice, due to elevation of bilirubin in the plasma. This elevation is due to overproduction of bilirubin or to failure of its excretion and is seen in numerous diseases ranging from hemolytic anemias to viral hepatitis and to cancer of the pancreas. 

The catabolism of haemoglobin yields haem, which is subsequently converted to bilirubin in a two-step process that takes place in the hepatocyte. First, the microsomal enzyme haem oxygenase cleaves the porphyrin ring of haem, generating biliverdin in an energy-utilising reaction. Following this, biliverdin is converted to bilirubin by the cytosolic enzyme biliverdin reductase. As the liver is the active site for biosynthesis of porphyrin and haem, deficiencies in some enzymes of the porphyrin pathway may lead to insufficient haem production and an increase in porphyrin levels, which causes acute porphyria attacks. 

T. S. C. Wang, Analytical Chemistry of Bilirubins New Methods, Caffeine Complexation, Stability, and Biosynthesis of Conjugates. Diss. Abstr. Int. 

Protoporphyrin IX is a precursor for the biosynthesis of heme, chlorophyll, and cytochrome. Bile pigment is also derived from heme. The structure of bilirubin, the main component of this bile pigment, is shown [7]. Bilirubin is also a main component of the crude drug Go-Oh (bezoar, concave) prepared from the unhealthy calculus in the gallbladder or bile duct of cattle. Bezoar is an animal preparation used for detoxification, as an antipyretic, and as a cardiotonic. The biosynthesis of chlorophylls and bacte-riochlorophylls from protoporphyrin IX has been reviewed [8]. 

Plasma proteins are manufactured in the liver and their serum levels are reduced when the ability of hepatocytes to synthesize proteins is impaired. The ammonia level rises when hepatocyte damage prevents biosynthesis of amnrania to urea. Bilirubin can increase as a result of either hepatocyte dysfunction or cholestasis. Prothrombin time increases because of the reduced availability of coagulation factors normally synthesized by hepatocytes. Sorbitol dehydrogenase (SDH) is a liver-specific enzyme that is released when... 

---