Cambridge Pre-U Biology

S14: Homeostasis

Learning Outcomes
■ describe the structure and function of the liver to include its role in blood sugar control,
deamination, transamination and detoxification
■ outline the causes, diagnosis, effects and treatment of type 1 and type 2 diabetes

■ explain the principles of operation of dip sticks containing glucose oxidase enzymes, and
biosensors that can be used for quantitative measurement of glucose.

S14.1  Structure of the liver

The liver is a large lobed organ located in the abdomen of mammals with a very good blood
supply through the hepatic artery and the hepatic portal vein. This high demand for blood
reflects the liver’s high level of metabolic activity in its homeostatic, immunological and
detoxification roles. Liver tissue consists of many thousands of lobules made up of specialised
liver cells, known as hepatocytes.
Figure S14.1 shows the position of the liver in the abdomen and surrounding organs. It
also shows that the liver receives oxygenated blood from the aorta via the hepatic artery and 1
deoxygenated blood from the stomach and intestines via the hepatic portal vein. The hepatic
portal vein also carries blood from the pancreas to the liver. This means that the hormones
insulin and glucagon are delivered directly to the liver when they are secreted.
Figure S14.2a shows the appearance of lobules in a section through liver tissue. At the edge
of each lobule are branches of the hepatic artery and the hepatic portal vein. Blood flows
from these branches through narrow blood spaces called sinusoids into the intralocular
vein – a branch of the hepatic vein in the centre of each lobule. Figure S14.2b shows the area
where sinusoids drain into a branch of the hepatic vein. Hepatocytes are arranged in rows
that radiate out from the central vein.

aorta
diaphragm posterior
blood vena cava
from
hepatic
artery blood to
hepatic
portal vein
blood
gall bile liver
bladder hepatic
portal
bile bile vein
duct
small
intestine

Figure S14.1  The gross structure of the liver and its associated organs and blood supply.
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Figure S14.2  Photomicrographs of liver tissue. a Liver lobules separated by connective tissue,
b an enlarged view of the area around a branch of the hepatic vein in the centre of a lobule.

branch of
hepatic portal vein Kupffer cell
(macrophage)
hepatocyte endothelial sinusoid
cell contains blood

branch of branch of bile canaliculus

hepatic artery 2
bile duct contains bile
branch of
hepatic vein

Figure S14.3  A simplified diagram of part of a liver lobule.

Each lobule is supplied with oxygen-rich blood via the hepatic artery and with nutrient-rich
blood from the gut via the hepatic portal vein. The blood from these two blood vessels mixes
in spaces between the hepatocytes known as sinusoids. The sinusoids carry the blood past
Kupffer cells to the intralobular vein, a branch of the hepatic vein which drains the blood
from the liver (Figure S14.2b). Between rows of hepatocytes, blind-ending canals called bile
canaliculi lead to the bile ducts, which carry bile to the gall bladder. Hepatocytes make bile
salts and bile pigments which flow along these bile canaliculi. The bile is stored in the gall
bladder and periodically released into the bile duct where it flows into the duodenum.

S14.2 Functions of the liver

Blood glucose control
Under the influence of insulin and glucagon, hepatocytes contribute to the regulation of
blood sugar (see ‘The control of blood glucose’, Chapter 14).

Deamination
Hepatocytes are responsible for the breakdown of excess amino acids into ammonia and keto
acids, and finally into urea (see ‘Excretion’, Chapter 14).

Transamination
During amino acid degradation, the amine group is transferred to a keto acid (usually α–
ketoglutarate) forming glutamic acid, a process known as transamination. This is catalysed
by specific aminotransferase enzymes.
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– –
COO COO

CH2 CH2
R R
CH2 CH2 +
+ +
H C NH3 + C O
C O H C NH3
COO– COO–
COO– COO–
α-ketoglutarate amino acid glutamic acid keto acid

The amine group from glutamic acid can then be transferred back to another keto acid
forming other amino acids, known as non-essential amino acids.
In mammals, only some of the amino acids can be synthesised by transamination (the
non-essential amino acids). Mammals lack the enzymes required for transamination of
around ten of the amino acids (known as essential amino acids) and so these need to be
supplied in the diet of the organism.
Example: the production of the non-essential amino acid alanine from aspartic acid.
aspartic acid + α-ketoglutarate → oxaloacetate + glutamic acid
glutamic acid + pyruvate → α-ketoglutarate + alanine

Detoxification
The hepatocytes contain enzymes which can inactivate a wide range of toxins in the blood.
This includes:
• the breakdown of various drugs (such as aspirin and morphine)
• the breakdown of insecticides (such as carbamates and pyrethroids)
• the dehydrogenation of alcohol
• the breakdown of hormones (such as oestrogen and insulin) 3

• the removal of lactate and ammonium ions from the circulation

The liver removes lactate produced in the blood as a result of anaerobic respiration. It can
convert this lactate to pyruvate using the enzyme lactate dehydrogenase. The pyruvate can
then be removed in two ways;
• Enzymes involved in gluconeogenesis convert pyruvate to glucose. The glucose can then
be used as a respiratory substrate or stored as glycogen.
• Pyruvate can be oxidised in the mitochondria to carbon dioxide and water (aerobic
respiration), releasing energy.
The Kupffer cells are specialised macrophages that line the sinusoids of the lobules. These
cells engulf damaged red blood cells, as well as any antigenic material such as bacteria that
have entered the hepatic portal vein from the gut.

S14.3 More about diabetes

The second form of diabetes is called non-insulin dependent or type 2 diabetes. This form
of diabetes begins later in life and may be due to:
• reduced production of insulin by the β cells of the pancreas
• reduced sensitivity of muscle and liver cells to insulin (insulin resistance).
Many cases of type 2 diabetes may have an underlying genetic cause, but the condition has
also been linked to lifestyle – with a poor diet (high in saturated fats and high in sugars) and
obesity being major contributory factors.
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S14.4 How ADH affects the kidneys

Antidiuretic hormone binds to specific AVPR2 receptors found on the cell surface
membrane of the cells lining the collecting ducts and distal convoluted tubules of the
nephron. These transmembrane receptors are coupled to a G-protein which is activated
when ADH binds. The activated G-protein then activates a membrane-bound enzyme
(see Fig 14.24) called adenylate cyclase which converts ATP to cAMP, a second messenger.
Through a cascade of reactions, an increase in the concentration of cAMP results in
the activation of phosphorylating enzymes which bring about the fusion of aquaporin-
containing vesicles with the cell surface membrane. These aquaporins fuse with the luminal
membrane so increasing the permeability of the cell to water, allowing greater reabsorption
of water.

S14.5 More about biosensors

A biosensor like the one in Figure 14.28 in the Coursebook allows people with diabetes to
check their blood to see how well they are controlling their glucose concentration.
A biosensor consists of a biological recognition layer (the specific enzymes), a
biotransducer component (which converts the chemical signal produced into an electrical
signal) and an electronic system which includes an amplifier (to increase the signal),
processor and display.

glucose + oxygen → gluconolactone + hydrogen peroxide

The oxygen diffuses across an oxygen-permeable membrane (Teflon) to an oxygen electrode.

Here it creates a current that can be displayed to represent glucose concentration – the more
glucose present then the lower the oxygen concentration diffusing across the membrane. As 4
the concentration of oxygen in the blood tends to remain constant, the drop in oxygen will
be proportional to the glucose concentration of the blood sample. This can be converted to
represent the blood glucose variable as a visual display.

Summary
■ The liver is composed of specialised cells called hepatocytes that have important roles in:
• Regulation of blood glucose
• Deamination of amino acids
• Transamination of amino acids by transferring an amine group to a keto acid
• Detoxification of drugs and poisons, including alcohol, ammonia and lactate
■ Type 1 diabetes occurs as a result of autoimmune destruction of pancreatic β cells, so that
insulin production is reduced or absent. In type 2 diabetes, insulin production may be
reduced and the body tissues fail to respond to the insulin that is present. Both type 1 and
type 2 diabetes result in raised plasma glucose concentration after a meal and can have
serious health consequences if not treated with insulin injections, drugs or lifestyle changes.
■ Biosensors use enzyme catalysed reactions to produce an electrical signal that can
then be amplified. They can be used to measure the blood glucose levels of people
who suffer from diabetes. Glucose reacts with oxygen to produce hydrogen peroxide.
An oxygen electrode can be used to measure the oxygen present and convert this into a
voltage for display. More glucose will mean less oxygen available.
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End-of-chapter questions
S14.1 W
 ith the use of diagrams of amino acids from Appendix 1 of the Coursebook,
show how transamination of an amino acid occurs.
S14.2 U
 sing figure 14.23 from the Coursebook, explain how the structure of a
hepatocyte is suited for a high metabolic function.
S14.3 Describe how the liver could bring about a reduction in blood glucose
concentration.