vi cũng có thể dẫn đến sự hình thành của các sản phẩm phản ứng độc hại. Với một số hóa chất chỉ có một phản ứng enzyme có liên quan, trong khi đó với các hợp chất khác, nhiều phản ứng, thường liên quan đến nhiều đường, cần thiết cho việc sản xuất các chất chuyển hóa phản ứng cuối cùng. | HEPATIC ELIMINATION 209 Figure Enterohepatic circulation as indicated by . Polar xenobiotic conjugates are secreted into the intestine via the bile duct and gall bladder. Conjugates are hydrolyzed in the intestines released xenobiotics are reabsorbed and transported back to the liver via the portal vein. the chemical can be reprocessed . biotransformed and eliminated. This process is called entero-hepatic circulation Figure . A chemical may undergo several cycles of entero-hepatic circulation resulting in a significant increase in the retention time for the chemical in the body and increased toxicity. The liver functions to collect chemicals and other wastes from the body. Accordingly high levels of chemicals may be attained in the liver resulting in toxicity to this organ. Biotransformation of chemicals that occur in the liver sometimes results in the generation of reactive compounds that are more toxic than the parent compound resulting in damage to the liver. Chemical toxicity to the liver is discussed elsewhere Chapter 14 . Active Transporters of the Bile Canaliculus The bile canaliculus constitutes only about 13 of the contiguous surface membrane of the hepatocyte but must function in the efficient transfer of chemical from the hepatocyte to the bile duct. Active transport proteins located on the canalicular membrane are responsible for the efficient shuttling of chemicals across this membrane. These active transporters are members of a multi-gene superfamily of proteins known as the ATP-binding cassette transporters. Two subfamilies are currently recognized as having major roles in the hepatic elimination of xenobiotics as well as endogenous materials. The P-glycoprotein ABC B subfamily is responsible for the elimination of a variety of structurally diverse compounds. P-glycoprotein substrates typically have one or more cyclic structures a molecular weight of 400 or greater moderate to low lipophilicity log Kow 2 and high hydrogen donor .
