Liver metabolism.

1. Mammalian Liver
• The Mammalian Liver The liver is the largest
gland in the body and the second largest organ
after the skin.
• The liver is situated under the diaphragm on the
right side of the abdominal cavity Numerous
metabolic reactions occur within the liver and it is
an important organ of homeostasis

2. Blood Supply
• The liver receives blood from two sources
• The hepatic artery delivers oxygenated blood to
the liver
• The hepatic portal vein delivers blood, rich in
digested food molecules, from the small intestine
Blood leaves the liver along the hepatic vein and
enters the vena cava

3. • The liver is composed of a large number of
lobules Each lobule contains many vertical rows
of liver cells (hepatocytes) arranged radially
around a central blood vessel called the central
vein Branches of the hepatic artery and hepatic
portal vein supply blood to the capillaries of each
lobule Running between the lobules in the
opposite direction to the blood, are fine ducts,
carrying bile from the liver cells towards the
main bile duct

4. • Blood flow molecules enter liver cells blood flows
into central vein bile from liver cells flow of bile Part
of Liver Lobule Hepatocytes bear numerous microvilli
at their surfaces in contact with the sinusoids,
thereby increasing the surface area for facilitating
the exchange of materials; numerous mitochondria
within the cytoplasm reflects their high demand for
ATP to provide for the numerous endergonic
reactions Branch of hepatic portal vein Liver cells;
Hepatocytes Sinusoid Phagocytic Kupffer cell Central
vein of lobule (to hepatic vein) Branch of hepatic
artery Branch to bile duct Bile canaliculus Fine
channels, called canaliculi, collect bile from the liver
cells and carry it towards the bile duct

5. • Sinusoids Sinusoids are dilated capillaries in which
the lining epithelial cells and basement membrane
are discontinuous Sinusoids have larger diameters
than other capillaries with distinct gaps in their
lining The structure of the sinusoidal capillaries
allows for the ready exchange of materials
(including macromolecules) between the blood
and the liver cells Epithelial lining cells Basement
membrane.
• Carbohydrate Metabolism Protein Metabolism
Lipid Metabolism Haemoglobin and Hormone
breakdown and Detoxification Storage of Vitamins
and Minerals Bile Production

6. • Carbohydrate Metabolism The liver’s major role in
the metabolism of carbohydrates is that of glucose
homeostasis
• Under the influence of the hormones insulin and
glucagon (secreted by the Islets of Langerhans of the
pancreas) and adrenaline from the adrenal glands,
blood glucose concentrations are regulated and
adjusted to meet the metabolic demands of the
tissues
• The digestion of polysaccharides and disaccharides in
the gut yields the monosaccharides glucose, fructose
and galactose; these sugars are transported to the
liver along the hepatic portal vein

7. • Carbohydrate Metabolism In the liver, most of
the fructose and galactose molecules are
converted to glucose; the liver plays a significant
role in the control of blood glucose
concentrations in three major ways:
• Glycogenesis; activation of the liver enzymes that
convert glucose into glycogen for storage
• Glycogenolysis; activation of the liver enzymes
that convert glycogen into glucose when blood
glucose levels fall
• Gluconeogenesis; activation of the liver enzymes
that convert non-carbohydrates into glucose in
response to low blood glucose concentrations

8. • Glycogenolysis; the conversion of stored
glycogen into glucose when blood sugar levels
fall glucagon and adrenaline Glycogenesis; the
conversion of glucose into glycogen when blood
sugar levels rise insulin
• Gluconeogenesis is the conversion of non-
carbohydrates, such as amino acids and glycerol,
into glucose by the liver When the demand for
glucose depletes the glycogen stores, non-
carbohydrate sources are converted by the liver
into glucose

9. Protein Metabolism
• During digestion, proteins are hydrolysed into
their constituent amino acids and transported to
the liver along the hepatic portal vein Unlike
glucose, excess amino acids cannot be stored in
the liver; excess dietary amino acids undergo
deamination and are also converted into glucose
and triglycerides Transamination reactions occur
in the liver; this involves the conversion of one
amino acid into another and is the process by
which non-essential amino acids are synthesised

10. • The fate of surplus amino acids within the liver
cells involves:
• Deamination; the removal of the amino group
from an amino acid, producing ammonia and a
keto acid; the toxic ammonia is converted into
urea, which is transported to the kidneys for
excretion; the keto acid may enter the
respiratory pathway to yield ATP or, may be used
for the synthesis of glucose and fatty acids
• Gluconeogenesis; liver cells can convert amino
acids into carbohydrate
• Lipogenesis; liver cells can convert amino acids
into fats

11. • Surplus amino acids cannot be stored and
undergo deamination in the liver
• The amino group of the amino acid, together with
a hydrogen atom, is removed to form ammonia
and a keto acid
• The highly toxic ammonia enters and is converted
into urea
• The keto acid either enters the respiratory
pathway and generates ATP, or it is converted into
carbohydrates or fats
• The less toxic urea is excreted by the kidneys

12. Lipid Metabolism
• The lipids are a diverse group of molecules and
include cholesterol, triglycerides and
phospholipids
• The liver synthesises, modifies, releases and
eliminates lipids, playing a major role in their
homeostatic regulation
• Surplus cholesterol and phospholipids are
eliminated in the bile; the liver manufactures
bile, which is stored in the gall bladder and
secreted into the duodenum of the gut

13. • The roles of the liver in lipid metabolism include:
Lipogenesis; the synthesis of triglycerides from
glucose when glycogen stores are depleted; the
resulting triglycerides can be stored or utilised in
the production of cholesterol and phospholipids
• The synthesis of cholesterol and phospholipids
The modification of cholesterol and triglycerides
(combined with liver proteins) to produce water-
soluble lipoproteins for transport to other body
tissues
• The elimination of surplus cholesterol and
phospholipids in the bile

14. • Liver cells synthesise triglycerides from glucose
or amino acids (lipogenesis) when glycogen
stores are full
• The liver synthesises most of the cholesterol and
phospholipid found in the body and regulates
their concentrations in the blood
• The resulting triglycerides can be stored or used
to synthesise other lipids, such as cholesterol and
phospholipids
• Excess cholesterol and phospholipid is removed
in the bile and delivered to the gut for
elimination

15. • The synthesis, release and elimination of
cholesterol and phospholipids is regulated by the
liver
• Surplus cholesterol and phospholipid is eliminated
in the bile
• Cholesterol and triglycerides are combined with
liver proteins to render them soluble for transport
in the blood (lipoproteins)

16. • Good’ and ‘Bad’ Cholesterol Low density lipoproteins
(LDLs) are loosely termed ‘bad cholesterol’ since
excess LDLs remain in the bloodstream and deposit
cholesterol in and around the muscle fibres in arteries
(forming fatty plaques); this may lead to
atherosclerosis (narrowing of the arteries) LDLs attach
to specific receptors on the surfaces of cells and are
taken into the cells by endocytosis where the
cholesterol is released When a cell’s cholesterol needs
are met, the production of LDL receptors is shut
down, and the receptors already present are gradually
removed; the lack of receptors raises plasma LDL
levels, making it more likely that plaques will develop
in the arteries

17. • Fatty deposits begin to build up in the artery
wall Fatty deposits (plaques) build up in large
quantities; calcium deposits harden the
arteries; blockage is extreme and blood flow is
seriously affected.
• High density lipoproteins (HDLs) are associated
with a decreased risk of atherosclerosis HDLs
remove excess cholesterol from body cells and
transport it to the liver for elimination;
accumulation of cholesterol in the blood is
prevented and the risk of fatty plaque
formation in the arteries is reduced ‘Good’ and
‘Bad’ Cholesterol.