Hemoglobin Breakdown

Presentation Notes on Hemoglobin Life Cycle / Span/ Fate and Breakdown Products & Pathway for Medical Biology Students in word/ .ppt/ .pdf Format

FATE OF HEMOGLOBIN

As stated previously, when the erythrocytes (RBC) become old, they rupture, mostly in spleen (as well as in the liver and bone marrow). The Hb, is liberated from the ruptured RBC and phagocytozed by the phagocytes of reticulo endothelialsystem.Within the phagocytes, the tetrapyrrole ring is opened up, that is, the haem is converted into a compound where the four pyrrole rings lie side by side.The iron is still attached with the tetrapyrrole straight chain compound and probably the globin also remains attached with it. Subsequently both globin and iron are removed. The tetrapyrrole straight chain compound thus formed (free from iron and globin) is called biliverdin.     
                             
Biliverdin is oxidized to form bilirubin. All these changes occur within the phagocyte of the reticuloendothelial system.'Bilirubin now comes out of the phagocyte and, in the plasma, combines with albumin and is transported in, the plasma as bilirubin-albumin complex. This complex is fre­quently called "free bilirubin" by the clinicians and clinical biochemists.

               The free bilirubin ultimately enters the liver and here the albumin is removed from the free bilirubin and most of the 'bilirubin is conjugated with glucuronic acid (a derivative of glucose), to form bilirubin glucuronides, which is water soluble. A small amount of bilirubin is conjugated with sulphate radicals to form bilirubin sulphate. The conjugated water soluble bilirubin is called "conjugated bilirubin".

The conjugated bilirubin is discharged into the biliary canaliculi and gets                                                    mixed up with bile. This is the main coloring matter of the bile.Via the bile, the conjugated bilirubin ultimately enters the duodenum. In the intestine, when it comes in contact with the intestinal bacteria, bilirubin glucuronide is hydrolyzed by bacterial enzymes and non-conjugated bilirubin, which also is, unfortunately, called free bilirubin, is formed (unfortunate, because the term 'free', can create a confusion; whether it means bilirubin albumin complex or it is bilirubin obtained by unconjugation of the glucuronides). This free bilirubin is reduced to form urobilinogens and sterco bilinogens. Part of the urobilinogens and stercobilino­gens are absorbed by blood which then circulate in the blood and is excreted via the urine. The rest (ie. that part which was not absorbed from the gut) is excreted via stool. Golden yellow color of the stool is due to these pigments (stercobilinogen), and if the stool be kept exposed to the sun and air, the color becomes blackish because of oxidation of these pigments.

The conjugation (with glucuronic acid) of bilirubin in liver is catalyzed by the enzyme glucurony ltransferase.Many drugs, especially some steroids compete with bilirubin for conjugating with glucuronic acid. Unless bilirubin conjugates with glucuronic acid it cannot be excreted via bile. So excessive use of these drugs often lead to accummulation of "free bilirubin" in the plasma (jaundice).

All conditions which produce excessive erythrocyte destruction, eg., malaria, mismatched blood transfusion, erythroblastosis fetalis, bites by some types of poisonous snakes, thus lead to excessive "free bilirubin' (ie, bilirubin-­albumin complex) formation, and jaundice, clinically called,hemolytic jaundice, develops. But the urine' does not contain free bilintbin in hemolytic jaundice, as the compound (ie, bilintbin-albumin complex) cannot pass the renal filter (owing to its big size). Instead, the urine contains excessive urobilinogen. The normal bilirubin concentration of plasma is between 0:5 to 1.0 mg/100 ml, which rises greatly in hemolytic jaundice.

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