Bilirubin transport

The porphyrin constituent of haem is reduced to bilirubin, transported to the liver and excreted in the bile as a glucuronide. Iron is recycled, transferred in the blood as transferrin and stored in tissues as ferritin. 

Wang, P., Kim, R.B., Chowdhury, J.R. and Wolkoff, A.W. (2003) The human organic anion transport protein SLC21A6 is not sufficient for bilirubin transport. The Journal of Biological Chemistry, 278, 20695-20699. 

There are various types of interference with the biliary system, and this can lead to bile stasis or damage to the bile ducts, ductules or canaliculi. In some cases such as with chlorpromazine, damage to the hepatocytes may ensue. Thus, some foreign compounds such as the antibiotic rifampicin, interfere with bilirubin transport and conjugation giving rise to hyperbilirubinaemia. Other compounds, icterogenin for example, cause bile stasis and bilirubin deposits in the canaliculi. This canalicular damage may also... 

Plasma bilirubin may be increased due to drug-related inhibition of uridine diphosphate glucuronosyltransferase (Zucker et al. 2001) or inhibitors of hepatic bilirubin transporters. By contrast, plasma bilirubin concentration may fall following administration of some mixed-function oxidase inducers, which may enhance the metabolism and excretion of bilirubin. 

Kamisako T, Kobayashi Y, Takeuchi K, Ishihara T, Higuchi K, Tanaka Y, Gabazza EC, Adachi Y. Recent advances in bilirubin metabolism research the molecular mechanism of hepatocyte bilirubin transport and its clinical relevance. J Gastroenterol 2000 35 659-664. 

Broderson, R. (1980). Bilirubin transport in the newborn infant reviewed with relation to ker-nicterus. J. Pediatr. 96 349-356... 

Hemoglobin Breakdown and Bilirubin Formation 385 Bilirubin Transport 385 Bilirubin Excretion 387 Urobilinogens 388 Jaundice 389 Neonatal Jaundice... 

The bilirubin transported in the plasma is eliminated from it by uptake in the liver cell. Again, the mechanism of transfer of bilirubin from plasma to hepatic cell is not known. 

Bilirubin formed in peripheral tissues is transported to the hver by plasma albumin. The further metabolism of bihtubin occuts primarily in the hver. It can be divided into thtee processes (1) uptake of bilirubin by hver parenchymal cells, (2) conjugation of bilirubin with glucuronate in the endoplasmic reticulum, and (3) secretion of conjugated bilirubin into the bile. Each of these processes will be considered separately. 

In the liver, the bilirubin is removed from albumin and taken up at the sinusoidal surface of the hepato-cytes by a carrier-mediated saturable system. This facilitated transport system has a very large capacity, so that even under pathologic conditions the system does not appear to be rate-limiting in the metabolism of bilirubin. 

Since this facilitated transport system allows the equilibrium of bilirubin across the sinusoidal membrane of the hepatocyte, the net uptake of bilirubin will be dependent upon the removal of bilirubin via subsequent metabolic pathways. 

Biliverdin is an early product of catabohsm and on reduction yields bilirubin. The latter is transported by albumin from peripheral tissues to the hver, where it is taken up by hepatocytes. The iron of heme and the amino acids of globin are conserved and reutilized. 

Another important function of albumin is its ability to bind various ligands. These include free fatty acids (FFA), calcium, certain steroid hormones, bilirubin, and some of the plasma tryptophan. In addition, albumin appears to play an important role in transport of copper in the human body (see below). A vatiety of drugs, including sulfonamides, penicilhn G, dicumarol, and aspirin, are bound to albumin this finding has important pharmacologic implications. 

The sinusoids transport both portal and arterial blood to the hepatocytes. The systemic blood delivered to the liver contains nutrients, drugs, and ingested toxins. The liver processes the nutrients (carbohydrates, proteins, lipids, vitamins, and minerals) for either immediate use or for storage, while the drugs and toxins are metabolized through a variety of processes known as first-pass metabolism. The liver also processes metabolic waste products for excretion. In cirrhosis, bilirubin (from the enzymatic breakdown of heme) can accumulate this causes jaundice (yellowing of the skin), scleral icterus (yellowing of the sclera), and tea-colored urine (urinary bilirubin excretion). 

Increased total, direct, and indirect bilirubin concentrations indicate defects in transport, conjugation, or excretion of bilirubin. 

Cui, Y., et al. Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6J. Biol. Chem. 2001, 276, 9626-9630. 

BBB). It is suggested75 that conformation-stabilizing intramolecularly hydrogen-bonded bilirubin is involved in transport of 90. 

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