Biochemistry of Specialized Tissues( liver)

Dr. Samina Hyder Haq

Assistant professor

Collage of Science

King Saud university

Liver characteristics The largest glandular organ in the body. It is one of the few internal organ capable of regeneration. 25% of

the liver tissue can regenerate into whole liver. Superficially has four lobes – right, left, caudate, and quadrate The falciform ligament:

Separates the right and left lobes anteriorly Suspends the liver from the diaphragm and anterior abdominal

wall. It is supplied with Hepatic art carries oxygen rich blood from

the aorta and The portal vein carries blood containing digested food from

the small intestine, stomach, spleen, pancrease and large intestine.

Anatomy of Liver

Liver Histology

Bile System

Liver Function1. It performs 500 jobs and 1,000 essential enzymes.

The functional unit is hepatocytes.

2. Produces and excrete bile

3. Perform several role in

Carbohydrate metabolism.

Excreted directly

Stored in gallbladder

gluconeogenisis

glucogenolysis

glycogenesis

Breakdown of insulin & other hormones

Functions of liver Protein metabolism

Lipid metabolismCholestrosynthesis

Lipogenesis(triglyceroids)

Serum Albumen

Soluble plasma Fibrenactin

Varios globulins

Liver function Produces coagulation factors Storage( Glycogen, vit B12, iron, Cu+,many other vitamins stored

in liver and perform function when activated by the liver Vit B, C, A, D, E, K

In the first trimester liver main site of RBC later bone marrow.

Liver responsible for Immunonological effect the reticuloendithelial system of the liver. Liver contain many analogical active cells act as a sieve for antigen carried to it, via portal system, get rid of bacteria, drug, chemicals.

Liver Function

Breakdown

Ammonia to urea

Iinsulin & other hormones

Haemoglobin creating metabolides(bilurbin

Breaks down toxins (drugs) Breakdowns metabolites of toxic substances Metabolise breakdown alcohol

Liver function Test1. ALT: alanine aminotransferase (Found primarily in

hepatocytes released when cells are hurt or destroyed.)

2. AST: aspartate aminotransferase (Found in many sources, including liver, heart, muscle, intestine, pancreas

3. Alkaline Phosphatase & Bilirubin(Liver AP rises with obstruction or infiltrative diseases (i.e., stones or tumors)

The most abundant bile acids in human bile are chenodeoxycholic acid (45%) and cholic acid (31%). These are referred to as the primary bile acids. Within the intestines the primary bile acids are acted upon by bacteria and converted to the secondary bile acids,

Structure of Conjugated cholic acids

Synthesis of Bile Within the liver the carboxyl group of primary and secondary bile

acids is conjugated via an amide bond to either glycine or taurine before their being re-secreted into the bile canaliculi. These conjugation reactions yield glycoconjugates and tauroconjugates, respectively. The bile canaliculi join with the bile ductules, which then form the bile ducts. Bile acids are carried from the liver through these ducts to the gallbladder, where they are stored for future use. The ultimate fate of bile acids is secretion into the intestine, where they aid in the emulsification of dietary lipids. In the gut the glycine and taurine residues are removed and the bile acids are either excreted (only a small percentage) or reabsorbed by the gut and returned to the

liver..

Composition of Bile A yellow-green, alkaline solution containing

bile salts, bile pigments, cholesterol, neutral fats, phospholipids, and electrolytes

Bile salts are cholesterol derivatives that: Emulsify fat Facilitate fat and cholesterol absorption Help solubilize cholesterol

Enterohepatic circulation recycles bile salts The chief bile pigment is bilirubin, a waste

product of heme

Gallbladder Thin-walled, green muscular sac on the

ventral surface of the liver Stores and concentrates bile by absorbing its

water and ions Releases bile via the cystic duct, which flows

into the bile duct

Regulation of bile Acidic, fatty chyme causes the duodenum to

release: Cholecystokinin (CCK) and secretin into the

bloodstream Bile salts and secretin transported in blood stimulate the liver to

produce bile Vagal stimulation causes weak contractions of the gallbladder. Cholecystokinin causes:

The gallbladder to contract The hepatopancreatic sphincter to relax

As a result, bile enters the duodenum

Regulation of bile release

Detoxification of Alcohol by liver Ethanol has been a part of the human diet for

centuries. However, its consumption in excess can result in a number of health problems, most notably liver damage.

Ethanol cannot be excreted and must be metabolized, primarily by the liver. This metabolism occurs by two pathways. The first pathway comprises two steps. The first step, catalyzed by the enzyme alcohol dehydrogenase, takes place in the cytoplasm:

:

Ethanol metabolism The second step, catalyzed by aldehyde

dehydrogenase, takes place in mitochondria.

ethanol consumption leads to an accumulation of NADH. This high concentration of NADH inhibits gluconeogenesis by preventing the oxidation of lactate to pyruvate. In fact, the high concentration of NADH will cause the reverse reaction to predominate, and lactate will accumulate. The consequences may be hypoglycemia and lactic acidosis.

The NADH glut also inhibits fatty acid oxidation. The metabolic purpose of fatty acid oxidation is to generate NADH for ATP generation by oxidative phosphorylation, but an alcohol consumer's NADH needs are met by ethanol metabolism. In fact, the excess NADH signals that conditions are right for fatty acid synthesis. Hence, triacylglycerols accumulate in the liver, leading to a condition known as “fatty liver.”

The second pathway for ethanol metabolism is called the ethanolinducible microsomal ethanol-oxidizing system (MEOS). This cytochrome P450-dependent pathway generates acetaldehyde and subsequently acetate while oxidizing biosynthetic reducing power, NADPH, to NADP+. Because it uses oxygen, this pathway generates free radicals that damage tissues. Moreover, because the system consumes NADPH, the antioxidant glutathione cannot be regenerated exacerbating the oxidative stress.

Liver mitochondria can convert acetate into acetyl CoA in a reaction requiring ATP. The enzyme is the thiokinase that normally activates short-chain fatty acids.

However, further processing of the acetyl CoA by the citric acid cycle is blocked, because NADH inhibits two important regulatory enzymes— isocitrate dehydrogenase and α-ketoglutarate dehydrogenase.

The accumulation of acetyl CoA has several consequences. First, ketone bodies will form and be released into the blood, exacerbating the

acidic condition already resulting from the high lactate concentration. The processing of the acetate in the liver becomes inefficient, leading to a buildup of acetaldehyde. This very reactive compound forms covalent bonds with many important functional groups in proteins, impairing protein function. If ethanol is consistently consumed at high levels, the acetaldehyde can significantly damage the liver, eventually leading to cell death.

Liver Cirrhosis

Liver damage(from excessive ethanol consumption occurs in three stages. 1. The first stage is the development of fatty liver.

2. In the second stage—alcoholic hepatitis—groups of cells die and inflammation results. This stage can itself be fatal.

3. In stage three—cirrhosis—fibrous structure and scar tissue are produced around the dead cells. Cirrhosis impairs many of the liver's biochemical functions. The cirrhotic liver is unable to convert ammonia into urea, and blood levels of ammonia rise. Ammonia is toxic to the nervous system and can cause coma and death. Cirrhosis of the liver arises in about 25% of alcoholics, and about 75% of all cases of liver cirrhosis are the result of alcoholism. Viral hepatitis is a nonalcoholic cause of liver cirrhosis.

Jaundice

Jaundice is a yellowish discoloration of the skin and of the whites of the eyes caused by abnormally high levels of the pigment bilirubin in the bloodstream.