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  • Title: [Bilirubin metabolism (author's transl)].
    Author: Seyfried H, Klicpera M, Leithner C, Penner E.
    Journal: Wien Klin Wochenschr; 1976 Aug 13; 88(15):477-82. PubMed ID: 793184.
    Abstract:
    The degradation of haemoglobin haeme of senescent red blood cells - involving NADPH-dependent haeme oxygenase and biliverdin reductase - in the reticuloendothelial cells of the spleen, bone marrow and liver accounts for 80 to 90% of the 250 to 300 mg of bilirubin formed in 24 hours. The remaining 10 to 20% derive from catabolism of other haemoproteins and from the destruction of maturing red blood cells in the marrow. In studies with isotopically-labelled metabolic precursors of haeme this fraction can be found in the early-labelled peak. In plasma virtually all the bilirubin is tightly bound to plasma proteins, largely albumin, because it is only sparingly soluble in aqueous solutions at physiological pH. In the sinusoids unconjugated bilirubin dissocates from albumin, enters the liver cells across the cell membrane through non-ionic diffusion and is bound by the two cytoplasmic proteins Y (or ligandin) and Z. Little is known about the transfer of unconjugated bilirubin from these binding proteins to the smooth endoplasmatic reticulum, where it is converted to a water-soluble ester glucuronide by bilirubin UDP-glucuronyl transferase. The physiological significance of non-glucoronide conjugates (sulphate, disaccharides) is only of minor importance. Following conjugation, bilirubin is transferred rapidly across the canalicular membrane into the bile canaliculi. This process is energy-dependent and occurs against a concentration gradient. The epithelial lining of the intestine and of the gall bladder, which can easily reabsorb lipid-soluble unconjugated bilirubin, is virtually impermeable to organic anions of the size and charge of conjugated bilirubin, thereby ensuring efficient excretion of this pigment. In the intestinal tract bilirubin is reduced to urobilinogen, which is subsequently reabsorbed to some extent into the enterohepatic circulation, removed from plasma by the liver and excreted unchanged in the bile. This rapid bacterial reduction of bilirubin makes it unlikely that unconjugated bilirubin is formed and absorbed to an appreciable degree. The residual part of urobilinogen is further reduced to urobilin, stercobilin and dipyrrolmethenes and excreted in the faeces.
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