Energy Metabolism

Explain the concept of food as a fuel for the production of energy in the body, and how energy
requirements vary during rest, exercise and starvation.

Food is a source of fuel for the body as it can be oxidised to produce energy in the body
It is a source of building blocks for the production of new cells and tissue
It is a source of chemicals that are necessary to conduct reactions within the body
ATP is the energy unit of the body
Proteins, lipids and carbohydrates that make up the major part of the food that we eat must be broken
down into smaller molecules before cells can use them as energy

At rest (The well-fed/ absorptive state)
Immediately after a meal, the blood glucose level rises and stimulates the release of insulin
Major target for insulin are liver, muscle and adipose tissue
Insulin promotes glycogen synthesis in liver and muscle
After glycogen stores are filled, the liver converts excess glucose to fatty acids and triglycerides
Brain tissue and red blood cells are insulin independent. They derive their energy from oxidising
glucose to CO
2
and water in both well-fed and normal fasting states. Only in prolonged fasting
does this change.
Starvation (prolonged)
Levels of glucagon markedly elevated
Lipolysis is rapid; resulting in excess acetyl CoA that is used for ketone synthesis
Levels of both lipids and ketones are thus increased in the blood
Muscles use fatty acids as the major fuel and brain adapts to using ketones for some of its energy
The shift from glucose to ketones as the
major fuel diminishes the amount of protein that must be degraded to support gluconeogenesis.

Exercise
The primary fuel used to support muscle contraction depends on the magnitude and duration of
exercise as well as the major fibres involved
Skeletal muscle has stores of both glycogen and some triglycerides
During moderately high, continuous exercise, oxidation of glucose and fatty acids are both
important, but after 1 to 3 hours of continuous exercise at this level, muscle glycogen stores
become depleted and the intensity of exercise declines to a rate that can be supported by oxidation
of fatty acids
During low-intensity exercise, fat oxidation predominates as the energy source with some
contribution by glucose


Describe the pathways involved in energy metabolism: glycolysis, Gluconeogenesis, beta-
oxidation, amino acid breakdown, TCA cycle and electron transport chain. For each, include the
cellular location, the major organs in which each pathway is active and the effect of starvation on
flux of substrates through the pathway.


This diagram is a very basic version of the human bodys metabolic pathway. The different processes are
further discussed below


Glycolysis
Metabolic pathway that turns glucose into pyruvate
It involves 10 definitive steps and 10 intermediate compounds
Occurs in cytosol of cell
If cell has mitochondria and oxygen, glycolysis is aerobic. If mitochondria or oxygen is lacking,
glycolysis may occur anaerobically (eg: exercising skeletal muscle)




Gluconeogenesis
Metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates
such as lactate and pyruvate
The process of gluconeogenesis helps keep blood glucose levels within critical limits
Occurs primarily in the liver (cytoplasm and mitochondria)
The pathways are promoted by glucagon and adrenaline and inhibited by insulin. In fasting, glycogen
reserves drop dramatically in the first 12 hours, during which time gluconeogenesis increases. After
24 hours, it represents the sole source of glucose.

Beta Oxidation
A process in which fatty acids molecules are broken down, through a series of intermediate steps, into
acetyl coenzyme A. Acetyl coenzyme A then enters the TCA cycle along with metabolites of
carbohydrates and proteins
Pathway is a repetition of four steps. Each four-step cycle releases one acetyl CoA and reduces NAD
and FAD (producing NADH and FADH
2
).
In muscle and adipose tissue (in the mitochondria), Acetyl CoA enters the TCA; in the liver ATP may
be used for gluconeogenesis and the acetyl CoA stimulates gluconeogenesis
In a fasting state, the liver produces more acetyl CoA from oxidation than is used in the citric acid
cycle. Much of this acetyl CoA is used to synthesise ketone bodies

Amino Acid breakdown
Proteins are made up of amino acids. Thus, to use proteins as a source of fuel, they must be broken
back down into amino acids
Amino acids released from proteins usually lose their amino group through transamination or
deamination
Body protein is catabolised primarily in muscle and in liver (in the mitochondria)
During prolonged fasting or starvation, protein may be used as an energy source

TCA cycle
Occurs in the mitochondria
Primary function is oxidation of acetyl Co A to carbon dioxide
Activity of the TCA is necessary irrespective of the fed or fasting state
Start and end products of the TCA
Electron Transport Chain (ETC)
Releases a large amount of energy
Occurs in mitochondria
Continues in next LO

Outline how chemical energy released from the oxidation of food molecules is used to drive ATP
synthesis and describe the role of the electron transport chain as an intermediate in this process.


Energy is extracted from food via oxidation
This occurs in four stages

Stage I
Foods that have been eaten are broken down into their primary components
I.e.: Carbohydrates into glucose, Proteins into amino acids and Fats into fatty acids
These components are absorbed
This occurs in the GIT

Stage II
Carbohydrates, proteins and fatty acids are further degraded by different pathways
Carbohydrates are broken down by glycolysis, amino acids by amino acid degradation and fatty
acids by oxidation
All the pathways use a common metabolic intermediate acetyl CoA
Most of the energy at this step is conserved in the chemical bonds of acetyl CoA
A small portion is conserved by reducing NAD to NADH and FAD to FADH
2


Stage III
The citric acid (or Krebs or TCA) cycle oxidises CoA to CO
2
.
The energy released in this process is primarily conserved by reducing NAD to NADH and FAD
to FADH
2


Stage IV
This stage is oxidative phosphorylation
The energy of NADH and FADH
2
is released via the electron transport chain (ETC)
It is used by an ATP synthase to produce ATP
It requires O
2








Specific to the ETC
Electrons are transported down a chain coupled to the transport of protons across the inner
membrane of the mitochondria
This occurs at three specific proton pumping sites in doing so, creating an electrochemical
gradient
Any energy not trapped as ATP is released as heat




References

Hansen, B. & Jorde, L. (N.D). USMLE Step 1 Lecture Notes. USA: Kaplan medical.
Sherwood, L. (2004). Human Physiology: From Cells to Systems (5
th
Edition). Australia: Thompson.
Lecture notes: Liver as integrator; Fasting and Exercise; Diet and nutrition