0:00 In this video, we're going to talk about bilirubin metabolism. 0:08 Bilirubin metabolism is important because hyperbilirubinemia is a condition 0:13 where you 0:14 have high amounts of bilirubin that can lead to jaundice, which is yellowing of 0:18 the skin 0:18 and of the eyes, for example, and this could indicate something sinister. 0:25 So bilirubin is formed by breakdown of heme present in hemoglobin. 0:32 So the story starts with an old red blood cell, which enters what's called the 0:36 reticuloendothelial 0:37 system, which is in your liver and in your spleen. 0:41 Here they are engulfed by macrophages. 0:44 The red blood cells contain many hemoglobin molecules, which are broken down to 0:50 heme and 0:51 globin, hence the name hemoglobin. 0:53 Heme is further broken down by two enzymes. 0:57 Heme oxygenase, followed by biliridin reductase, forming bilirubin and iron. 1:04 The iron and the globin is recycled to make more red blood cells. 1:14 The bilirubin formed is in an unconjugated form, so it's unconjugated bilirubin 1:20 , and 1:20 it is lipid soluble. 1:24 And so it has to bind to something, and albumin is the protein which acts as a 1:29 transporter. 1:30 So this unconjugated bilirubin is bound to albumin, but it also can bind to 1:35 other things 1:35 such as high density lipoproteins, and less often, it can circulate freely in 1:41 an unbound 1:41 form. 1:44 Biilirubin is also formed by the breakdown of other things, such as myoglobin 1:49 and cytochrome 1:50 enzymes. 1:51 Anyway, this albumin bilirubin complex circulates around and enters the liver 1:56 system where disassociates. 1:59 The unconjugated bilirubin is taken up efficiently by the hepatocytes, while 2:03 the albumin remains 2:04 in circulation. 2:07 Biilirubin enters the hepatocytes through facilitated diffusion, essentially 2:10 through 2:10 a concentration gradient. 2:13 Here they undergo what is called glucuronidation. 2:17 This process makes substances such as the bilirubin more water-soluble, which 2:23 allows 2:24 it to be excreted in bile and in urine. 2:29 Glucuronidation is carried out by a family of enzymes called uridine, diphospho 2:36 glucuronate, 2:38 glucuronosoltransferase, or UGT. 2:42 In the case of bilirubin, it is bilirubin UGT. 2:49 The unconjugated bilirubin is now conjugated bilirubin, and is water-soluble. 2:55 It is secreted into the bilirubin system, and is a component of bile. 3:02 Conjugated bilirubin travels down the bile duct, where it joins with the 3:05 pancreatic duct, 3:07 and into the duodenum through the ampulovata. 3:11 The conjugated bilirubin is now in the small intestine, where it continues its 3:17 journey. 3:18 Majority of bilirubin here is conjugated, 98% obviously, and only a small 3:24 proportion 3:25 is unconjugated bilirubin. 3:29 Conjugated bilirubin remember is water-soluble, and so it is not absorbed 3:34 across the lipid 3:35 membrane of the small intestinal epithelium. 3:38 In comparison, the unconjugated bilirubin fraction is partially reabsorbed, and 3:45 undergoes 3:47 interohapatic circulation, which is where it travels through the portal system 3:52 back 3:52 to the liver, so interohapatic liver circulation. 3:59 This unconjugated bilirubin can then undergo glucuronidation again to become a 4:04 conjugated 4:05 bilirubin and water-soluble. 4:08 Going back to this conjugated bilirubin actually continues travelling to the 4:12 large intestine, 4:14 where it is exposed to so much bacteria. 4:17 Here the bilirubin is reduced by bacterial enzymes to a series of molecules 4:22 termed urobulinogens. 4:28 Urobulinogens are partly absorbed in the bowel, and undergoes again interohap 4:34 atic circulation, 4:37 where the urobulinogen will enter the liver to get processed again. 4:41 Now the fraction that is actually not cleared by the liver will enter the 4:46 general circulation 4:47 and is partly excreted in urine. 4:51 Urobulinogen gives urine its yellow color. 4:58 Majority of urobulinogens is actually excreted in feces. 5:02 The urobulinogens here are further oxidized to form urobilins, including a stur 5:02 cobilin. 5:11 Oxidized urobulinogens, which I mentioned, gives feces its brown color. 5:19 So in summary, bilirubin is a breakdown product of hemoglobin. 5:22 Initially it is unconjugated, enters the liver, and becomes conjugated, which 5:29 is water-soluble. 5:30 It then gets further digested, oxidized by bacteria, and this oxidized form is 5:37 urobulinogen. 5:39 It can be reabsorbed, or excreted in feces. 5:42 And if you have high amounts of bilirubin, this can lead to jaundice, which is 5:45 yellow 5:45 in the skin and of the conchunctiva. 5:48 High amounts of bilirubin, hyperbilirubinemia, can be an indication of an 5:53 underlying disease. 5:55 This will be discussed in a separate video. 6:00 [MUSIC]
