Wk 9 A Matter of Opinion
LO: ENERGY METABOLISM
With regard to the production of energy:
a) Describe in overview the role of carbohydrates, fats and proteins in providing energy to the major
organs of the body (liver, muscle, heart, brain) in the fed state.






Carbohydrates, fats and proteins are absorbed from the GIT -> enter bloodstream-> supplied to organs.
Nutrients rapidly removed from the blood either directly oxidised to provide energy or stored (energy reserve for
periods of fasting).
Storage organs are adipose tissue (fat storage), liver (glycogen and some fat) and muscle (glycogen and some fat).
For several hours after food ingestion there is an abundance of circulating nutrients -> trigger secretion of insulin
and inhibit the release of glucagon.
Liver is the nutrient synthesis and distribution centre.
After a meal the liver is the first organ to receive nutrients from the GIT via the portal blood supply, then muscle,
brain and adipose tissues.
Carbohydrates
1.
Liver increases its uptake of glucose as the glucokinase now works at higher concentrations of glucose and converts it to
glucose-6-phosphate.
2. Liver- glycogenesis  synthesizing glycogen from excess glucose (via glycogen synthase)
3. Glycolytic rates in the liver are also increased due to the elevated insulin: glycogen ratio. This produces acetyl CoA which
can be used for fatty acid synthesis which go on to form triacylglycerides (TAG) which is then transported via the blood
to the adipose tissue (activated by insulin), or energy production via the TCA cycle for hepatic anabolic activity.
4. Gluconeogenesis is inhibited during the fed state due to the high insulin.
5. Muscle- glucose is converted into muscle glycogen. The uptake of glucose in muscle cells is stimulated by insulin.
6. Brain- uptake of glucose for oxidative phosphorylation.
7. Adipose Tissue- uptake of triacylglycerides (TAG) from the blood which have been synthesised from glucose. Storage of
triacylglycerides (TAG) in tissue (activated by insulin)
NOTE: Glycogen stores in the liver are used primarily to maintain blood glucose concentration whereas muscle glycogen is
not reconverted into glucose for export to other tissues. Muscle glycogen only provides energy for the activities of muscle
cells.
Fats
Fats comprise the major energy reserve of the body and being present in the diet, are also synthesised from excess dietary
carbohydrate and protein.
1. Fat acid synthesis is stimulated by insulin which stimulates increased Acetyl CoA and NADPH production through its
effects on glycolysis. In fact, in the liver and adipose tissue, most acetyl CoA produced is used for fat synthesis.
2. Triacylglycerol synthesis from fatty acids is also increased and transported to muscle tissue to use as energy, or to
adipose tissue for storage. These are stimulated by insulin.
Proteins/ Amino Acids
Proteins are absorbed in the small intestine -> free amino acids in the body. This pool of free amino acids is constantly
replenished by ingested amino acids or degraded body proteins and steadily loses amino acids by incorporation into new
tissues. Alanine, glutamic acid, glutamine and glycine are the four major amino acids in the pool.
Adipose tissue has an increase influx of glucose and dietary fat after a meal due to the effects of insulin. The adipocytes
increase glucose transport and glycolysis while dietary fats are stored as triacylglycerol synthesis increases.
Skeletal muscle also increases its uptake of glucose in the fed state as well as glycogen synthesis  due to insulin. Fatty acids
are transported, however are of secondary importance as the major fuel of muscle in the well-fed state is glucose. Amino
acid uptake is also increased as expected to replace degraded muscle protein since the last meal.
The Brain exclusively uses glucose for fuel in the fed state. Fatty acids don’t cross the BBB efficiently.
b) How are the body's tissue components (carbohydrates, fats and proteins) mobilised during fasting?
Carbohydrates
1.
2.
3.
Blood glucose from the diet starts to run out (3-4 hours post-meal), insulin levels decrease and glucagon levels increase
(produced in pancreatic beta and alpha cells, respectively). The increased glucagon to insulin ratio causes rapid
mobilisation of liver glycogen, which is exhausted within the first 8-12 hours.
The liver first uses glycogen degradation (glycogenolysis), then gluconeogenesis to maintain blood glucose levels.
Gluconeogenesis in the liver begins 4-6 hours after the last meal as liver glycogen diminishes.
Fats
Wk 9 A Matter of Opinion
1.
2.
3.
LO: ENERGY METABOLISM
Under starvation or stress, fatty acids are mobilised from triacylglycerol deposits in adipose tissue for utilisation by the
muscle and liver, where they are activated and split into glycerol and fatty acids, for -oxidation, resulting in acetyl-CoA,
which can then be utilised by the TCA cycle. This is primarily activated by glucagon.
In the post-absorptive state in starvation fatty acid oxidation from adipose tissue provides the liver its major source of
energy. It doesn’t use glucose for itself.
The liver also uniquely synthesises ketone bodies from the fatty acid for use as fuel by peripheral tissue. Occurs when
acetyl CoA from fatty acid metabolism exceeds the oxidative capacity of the TCA cycle in the liver. Important as ketone
bodies can be used as an alternate fuel source by most tissues including the brain. This preserves the need for
gluconeogenesis from amino acids thus reducing the degradation of essential protein.
Protein/ Amino Acids:
1.
2.
3.
4.
5.
6.
Major source for gluconeogenesis are glucogenic amino acids.
Body’s stores of protein are constantly being hydrolysed to amino acids and resynthesised.
Most protein burned during starvation comes from the liver, spleen and muscles
In the presence of low insulin and high cortisol, muscle protein breakdown is increased and protein synthesis is
decreased, releasing the amino acids into the blood.
Glucagon stimulates amino acid uptake in the liver.
Amino acid breakdown involves transfer of the N group to a keto-acid acceptor such as -Ketoglutarate
(transamination), followed by the removal of the N group (deamination) to form ammonia and leaving a carbon
skeleton:
 Most of the ammonia (NH4+) formed by the deamination of Amino Acids in the liver is converted to urea which is
excreted in the urine as a waste product
 The carbon skeletons of these amino acids are then converted to oxaloacetate where they can be used for
gluconeogenesis
 As glycogen stores are gradually depleted, gluconeogenesis becomes increasingly active, until 100% of the body’s
glucose is produced by this process.
Overview of the fasting state
Adipose tissue due to the low levels of insulin, depresses glucose uptake and therefore less fatty acid and triacylglycerol
synthesis. Also circulating adrenalin activates hormone sensitive lipase and triacylglycerol is broken down to fatty acids. The
fatty acids are released into the blood and bound to albumin for transport to various tissues for fuel. Fatty acid uptake by
adipose tissue is also depressed.
Skeletal muscle uptake of glucose is depressed as it does so via insulin-dependent transport proteins and insulin levels are
low during starvation. Initially the muscle uses up its glycogen stores to produce glucose. As it can’t release the glucose into
the blood, because it lacks glucose-6-phosphatase, the glucose enters glycolysis. After this, inside the first two weeks of
starvation, skeletal muscle uses both ketone bodies and fatty acid oxidation for fuel. After about 3 weeks skeletal muscle
switches exclusively to fatty acid oxidation. Muscle protein is degraded to supply amino acids for gluconeogenesis in the liver
during the first few days of starvation. After several weeks of starvation this muscle degradation is minimised to preserve
muscle and also the brain has decreased its need for glucose by now using ketone bodies.
The Brain during the first few days of starvation uses glucose exclusively. In prolonged starvation its switches from glucose to
ketone bodies and reduces the need for gluconeogenesis from amino acids derived from muscle protein as gluconeogenesis
would be unsustainable at the rates required.
c) How are blood glucose levels maintained?




The maintenance of blood glucose concentrations is achieved by the liver and kidneys (lesser extent).
Continual supply of glucose is necessary for the nervous system and erythrocytes.
Even when fat is supplying the majority of caloric needs- still a requirement for a basal supply of glucose.
Glucose is delivered by the blood and is derived from the diet, gluconeogenesis (conversion of amino acids,
propionate and lactate into glucose) and glycogenolysis (glucose derived glycogen stores).
Metabolic and Hormonal Controls of Blood [Glucose]
Glucokinase/ Hexokinase
 Hexokinase is inhibited by glucose-6-phosphate but glucokinase (found only in the liver and essentially performs the
same catalytic reaction as hexokinase) is not affected by the concentration of glucose-6-phosphate, therefore, liver
uptake of glucose can exceed that of other tissues and organs.
Insulin
 Produced by beta cells of islets of Langerhans (pancreas).
 Secreted in response to hyperglycaemia.
 Triggers for insulin release are: amino acids, free fatty acids, ketone bodies, glucagon, secretin and the drug tolbutamide.
 Adrenaline and noradrenaline block insulin release.
Wk 9 A Matter of Opinion

LO: ENERGY METABOLISM
Insulin causes uptake of glucose into adipose tissues and muscle tissue due to recruitment of insulin transporters ->
enhances glucose uptake.
 There is no direct effect of insulin on glucose uptake by hepatic cells but it does enhance it indirectly through actions on
enzymes controlling glycolysis and gluconeogenesis.
Glucagon
 Produced by α-cells of pancreas.
 Secretion is stimulated by hypoglycaemia.
 Causes glycogenolysis in liver by activating phosphorylase.
 Does not affect muscle phosphorylase.
 Enhances gluconeogenesis from amino acids and lactate.
Growth Hormone
 Secretion of Growth Hormone from the anterior pituitary stimulated by hypoglycaemia and as such decreases the
glucose uptake in certain tissues eg muscle.
 Mobilises free fatty acids from adipose tissue (which in turn inhibits glucose utilisation).
 Chronic administration of Growth Hormone may lead to diabetes as it produces hyperglycaemia which stimulates insulin
release, eventually causing β-cell exhaustion.
Glucocorticoids
 Secreted by adrenal cortex.
 Increase gluconeogenesis.
 Inhibit utilization of glucose in extrahepatic tissues.
 Antagonistic to insulin.
Adrenaline / Noradrenaline
 Secreted by adrenal medulla in response to stress stimuli (eg fear, excitement, hemorrahage, hypoglycaemia etc).
 Stimulates glycogenolysis in liver and muscle by stimulating phosphorylase.
 MUSCLE – glycogenolysis forms lactate (no G6Pase).
 LIVER – main product in increased [glucose] in blood.
Thyroid Hormone
 Hyperthyroidism – fasting blood glucose is elevated.
 Hypothyroidism – fasting blood glucose is low (decreased ability to utilize glucose and less sensitive to insulin).
The Brain
 The brain switches to ketone bodies in periods of starvation to conserve glucose and protein.
The Role of the Kidneys
 Kidneys have regulatory effect if [glucose] in blood is too high.
 Capacity of tubular system in kidneys to reabsorb glucose is limited to 350mg/min of glucose.
 When there is increased [glucose], the excess glucose passes into urine, resulting in GLYCOSURIA.
 Renal threshold for glucose is 9.5-10.0mmol / L of venous blood glucose concentration.