Bookshelf

Function

Bile Production

Bile is an important fluid as it helps excrete material not excreted by the kidneys and aids in the absorption and digestion of lipids via the secretion of bile salts and acids. Bile is produced by hepatocytes and is mainly composed of water, electrolytes, bile salts, bile acids, cholesterol, bile pigment, bilirubin, and phospholipids, in addition to other substances. Bile is secreted from hepatocytes into the bile canaliculi, where it travels from smaller ducts to the larger ducts, eventually ending up in the duodenum or being stored in the gallbladder for storage and concentration as determined by the duct and sphincter of Oddi pressures. Following secretion of bile into the duodenum, it undergoes enterohepatic circulation, where it performs its job in the bowel, and bile components that are not excreted are recycled by conversion into bile acids by gut bacteria for reuse by absorption in the ileum and transported back to the liver.

Bạn đang xem: Bookshelf

Fat-Soluble Vitamin Storage and/or Metabolism

Xem thêm : How to Prune Ginkgo Tree

Most fat-soluble vitamins reach the liver via intestinal absorption in the form of chylomicrons or VLDL. The liver stores and/or metabolizes fat-soluble vitamins. As discussed earlier, vitamin A is stored in Ito cells. It can undergo oxidation into retinal followed by retinoic acid for phototransduction, or retinoic acid can be conjugated into glucuronide for secretion into bile. Whether vitamin D3 comes from the skin, animal products, or plant products, it must undergo 25-hydroxylation by the hepatic CYP-450 system, which is further hydroxylated in the kidney to achieve its functional form. The hepatic CYP-450 system then hydroxylates carbon 24 to render vitamin D inactive. The liver receives vitamin E in its alpha and gamma-tocopherol forms. Alpha-tocopherol is integrated with VLDL or HDL in the liver and is then secreted back into circulation while the liver metabolizes the gamma-tocopherol form for excretion. While vitamin K is not stored or metabolized in the liver, its presence is essential as the liver enzyme gamma-glutamyl carboxylase requires it for gamma-carboxylation of coagulation factors II, VII, IX, X, and protein C and protein S.

Drug Metabolism

Another critical function of the liver is metabolism and/or detoxification of xenobiotics. The liver uses lysosomes for some of these substances, but biotransformation is a major route of metabolism and detoxification. The liver functions to transform xenobiotics mainly by converting them from a lipophilic form to a hydrophilic form through 2 reactions: phase I and phase II. These reactions mainly take place in the smooth endoplasmic reticulum of hepatocytes. Phase I reactions create a more hydrophilic solute via oxidation, reduction, and hydrolysis using primarily the cytochrome P450 (CYP450) family of enzymes. The product of phase I has an oxygen species that reacts better with enzymes involved with phase II reactions. Phase II reactions conjugate the metabolites created in phase I to make them more hydrophilic for secretion into blood or bile. There are three main avenues for conjugation performed in phase II reactions: conjugation to glucuronate, glutathione, or sulfate. Conjugation to glucuronate, such as with bilirubin, takes place in the smooth endoplasmic reticulum. Substances undergoing sulfate conjugation, such as alcohols, are usually done in the cytosol due to the location of the needed enzymes. Most glutathione conjugation occurs in the cytosol, with a minority occurring in the mitochondria. It is essential that glutathione is reduced, and depletion of reduced glutathione for conjugation can allow the buildup of toxic metabolites, as seen in acetaminophen overdose. Some describe the transport of metabolites produced from these reactions as phase III. Other organs, such as the kidney and gut, can aid drug metabolism. Multiple factors such as age, gender, drug-drug interactions, diabetes, pregnancy, liver or kidney disease, inflammation, or genetics, to name a few, affect drug metabolism. [3]

Xem thêm : Aging in Place

Bilirubin Metabolism

The liver plays a significant role in the breakdown of heme. Hemolysis takes place in multiple locations throughout the body, including the liver, spleen, and bone marrow. Heme is broken down into biliverdin, which is then reduced to unconjugated bilirubin. The liver receives unconjugated bilirubin bound to albumin from the circulation. The unconjugated bilirubin then undergoes conjugation via the uridine diphosphate glucuronyltransferase (UGT) system, a phase II process, to become hydrophilic. The newly conjugated bilirubin is then secreted via bile canaliculi into the bile, or small amounts dissolve in the blood, where it then gets filtered for excretion by the kidneys. Most conjugated bilirubin enters the bile and is excreted with bile in feces as it is not absorbable by the intestinal wall. Some bilirubin is converted to urobilinogen or unconjugated bilirubin by gut bacteria for reabsorption to undergo enterohepatic circulation.[4][5]

Other Functions

The liver plays a role in thyroid hormone function as the site of deiodination of T4 to T3. The liver manages the synthesis of nearly every plasma protein in the body, and some examples include albumin, binding globulins, protein C, protein S, and all the clotting factors of the intrinsic and extrinsic pathways besides factor VIII.

Nguồn: https://buycookiesonline.eu
Danh mục: Info