Download Biochemistry of Specialized Tissues( liver)

Biochemistry of
Specialized Tissues( liver)
Dr. Samina Hyder Haq
Assistant professor
Collage of Science
King Saud university
Liver characteristics
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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 Function
It performs 500 jobs and 1,000 essential enzymes.
The functional unit is hepatocytes.
Excreted directly
2. Produces and excrete bile
Stored in gallbladder
3. Perform several role in
gluconeogenisis
Carbohydrate metabolism.
1.
glucogenolysis
glycogenesis
Breakdown of insulin & other
hormones
Functions of liver
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Protein metabolism
Serum Albumen
Soluble plasma Fibrenactin
Varios globulins
Cholestrosynthesis
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Lipid metabolism
Lipogenesis(triglyceroids)
Liver function
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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
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In the first trimester liver main site of RBC later
bone marrow.
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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
Ammonia to urea
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Breakdown
Iinsulin & other hormones
Haemoglobin creating metabolides(bilurbin
Breaks down toxins (drugs)
Breakdowns metabolites of toxic substances
Metabolise breakdown alcohol
Liver function Test
1.
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)
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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
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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
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A yellow-green, alkaline solution containing
bile salts, bile pigments, cholesterol, neutral
fats, phospholipids, and electrolytes
Bile salts are cholesterol derivatives that:
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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
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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
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Acidic, fatty chyme causes the duodenum to
release:
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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
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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.
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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:
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Ethanol metabolism
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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.
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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.
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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.
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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.
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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.
2.
3.
The first stage is the development of fatty liver.
In the second stage—alcoholic hepatitis—groups of cells die and
inflammation results. This stage can itself be fatal.
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
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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.