The brain controls all the body’s vital functions and therefore has to have a constant supply of fuel.

In the Fed state (two - four hours after ingestion of a normal meal) the brain uses its preferred
source; glucose as it can cross the blood brain barrier and it uses this to maintain the membrane
potentials and for the synthesis of neurotransmitters. The brain uses the enzyme hexokinase to
activate glycolysis and this enzyme has a low Km / high affinity for glucose so there is no
competition with the brain for glucose.
Skeletal muscle fuel depends on the activity level with the active muscle preferring glucose
and resting muscle preferring fatty acids. Amino acids can also be used by skeletal muscles
occasionally. Cardiac muscle has a completely aerobic metabolism and uses glucose, fatty acids
and ketone bodies as fuels.
The role of adipose tissue is to store energy in the form of fat. The adipocytes esterify fatty
acids (FA) into triacylglycerols (TAGs) which is then stored. The adipocytes use an intermediate
from glycolysis to form glycerol-3-phosphate and so therefore use glucose as a fuel.
The liver is a major organ as several processes which help control the metabolic fuels in the
body take place there e.g. making glucose from glucogenic fuels (gluconeogenesis) and
deamination of amino acids.The liver receives the absorbed dietary fuel from the small intestine
first via the hepatic portal vein. During the Fed state, most of the glucose it receives is not used as
fuel but its stored as glycogen. The main sources of energy the liver uses are fatty acids and alpha
keto-acids from the degradation of amino acids.
The kidney is responsible for the filtering and excretion of waste and toxic substances from
blood as well as osmoregulation. During the fed state, the kidney takes its energy requirements
from glucose and fatty acids.

Fasting

Fasting is the period starting from four hours after ingestion of a meal and no nutrients have been
taken in during that time. causes the levels of glucose, amino acids, TAGs in the plasma to fall. The
fall in glucose levels causes an increase in glucagon secretion and a decrease in insulin secretion
from the pancreas. This triggers a set of catabolic reactions to maintain a constant supply of
glucose to the brain.

The glucagon signals the fasting state and stimulates glycogen breakdown in
hepatocytes(glycogenolysis). It does this by binding to the receptors in the cells leading to
phosphorylation and activation of .......
The liver also converts amino acids from breakdown of muscle protein, lactate from anaerobic
metabolism in muscle and glycerol from breakdown of TAGs to glucose - gluconeogenesis. This
releases glucose. The entry of glucose into muscle and adipose tissue decreases due to low levels
of insulin, as they have insulin dependent transporters (GLUT 4) and so more glucose can go to
the brain which has insulin independent GLUT 1 transporters. The liver also synthesises ketone
bodies which can cross blood brain barrier and be used by the brain.

The liver Beta oxidation of fats .......

The liver cannot use the ketone bodies as they lack the transferase enzyme needed for the.........

Hormone sensitive lipase enzymes are activated by glucagon and hydrolyse TAGs in adipose
tissue to glycerol which goes to the liver and fatty acids which are released into the blood and
transported to a range of tissues to be used as fuel. The fatty acids are also converted to acetyl
CoA which enters the Krebs cycle therefore producing energy for the adipose tissue.

During first few days of fasting because of low insulin levels, there is rapid breakdown of skeletal
muscle protein into amino acids which are transported to the liver. These muscles also have a store
of glycogen which they can use to make pyruvate in glycolysis but they cannot unlike the liver,
metabolise glycogen into glucose because they do not have the glucose - 6 - phosphotase enzyme
to hydrolyse the glucose - 6 - phosphate back into glucose. The skeletal muscle use fatty acids and
ketone bodies synthesised in liver as fuels during fasting to conserve glucose.

Because of gluconeogenesis, there is a lot of nitrogenous waste product in the form of urea that
needs to be excreted by the kidneys because of the conversion of the amino acids.

Starvation

As starvation (prolonged fasting from two days onwards) continues, our body protein and fat levels
are severely depleted. This leads to muscle wastage and when the body loses one third of its total
protein it has fatal consequences. There are final mechanisms to counteract the rate of depletion of
protein. The kidney becomes responsible for 50% of gluconeogenesis and so the kidneys
contribute to the glucose in the blood. Also more ketone bodies are recovered form the kidney and
the muscles use fatty acids rather than the ketone bodies to make ATP. This causes the levels of
ketone bodies in the blood to rise so the brain can now use more ketone bodies instead of glucose.
This reduces the need for gluconeogenesis and so the rate of breakdown of muscle for amino
acids decreases which decreases rate of muscle wastage / proteolysis. This also leads to fall in
deamination of amino acids and so urea production is decreased.The rase in ketone bodies also
limits lipolysis for the same reason. The liver and adipocytes continue to use fatty acids during
prolonged starvation.

Death will occur with continues starvation due to impairment of the immune system which needs
proteins to make antibodies.