INTEGRATION OF METABOLISM

Glycolysis:

The degradation of glucose to pyruvate or

lactate generates 8 ATP.

Pyruvate is converted to acetyl CoA.

Fatty acid oxidation:

Fatty acids undergo sequential degradation

with a release of acetyl CoA.

The energy is trapped in the form of NADH &

FADH2

Degradation of amino acids:

Amino acids, when consumed in excess than

required for protein synthesis, are degraded &

utilized to meet the fuel demands of the body.

The glucogenic amino acids can serve as

precursors for the synthesis of glucose

The ketogenic amino acids are the precursors

for acetyl CoA.

Citric acid cycle:

Acetyl CoA is the key & common metabolite,

produced from different fuel sources

(carbohydrates, lipids, amino acids).

Acetyl CoA enters TCA cycle & oxidized to CO2.

Most of the energy is trapped in the form of

NADH & FADH2.

Oxidative phosphorylation:

The NADH & FADH2, produced in different

metabolic pathways, are finally oxidized in

the electron transport chain (ETC).

The ETC is coupled with oxidative

phosphorylation to generate ATP.

Hexose monophosphate shunt:

It is primarily concerned with the liberation

of NADPH & ribose sugar.

NADPH is utilized for the biosynthesis of

several compounds, including fatty acids.

Ribose is an essential component of

nucleotides & nucleic acids.

Gluconeogenesis:

The synthesis of glucose from non-

carbohydrate sources constitutes

gluconeogenesis.

Several compounds (e.g. pyruvate, glycerol,

amino acids) can serve as precursors for

gluconeogenesis.

Glycogen metabolism:

Glycogen is the storage form of glucose,

mostly found in liver & muscle.

It is degraded (glycogenolysis) & synthesized

(glycogenesis) by independent pathways.

Glycogen effectively serves as a fuel reserve

to meet body needs.

The metabolic pathways are controlled by

four different mechanisms.

1. The availability of substrates

2. Covalent modification of enzymes

3. Allosteric regulation

4. Regulation of enzyme synthesis.

Liver: The body's central metabolic clearing house.

Carbohydrate metabolism:

Increased glycolysis, glycogenesis & HMP shunt &

decreased gluconeogenesis.

Lipid metabolism:

Increased synthesis of fatty acids & TAG.

Protein metabolism:

Increased degradation of amino acids & protein

synthesis.

Adipose tissue:

Adipose tissue is the energy storage tissue.

Carbohydrate metabolism:

The uptake of glucose is increased &

increase in glycolysis & HMP shunt.

Lipid metabolism:

The synthesis of fatty acids & TAGs is

increased.

The degradation of TAGs is inhibited.

Skeletal Muscle:

Carbohydrate metabolism:

The uptake of glucose is higher & glycogen

synthesis is increased.

Lipid metabolism:

Fatty acids are fuel sources for skeletal muscle.

Protein metabolism:

Incorporation of amino acids into proteins is

higher.

Brain:

Carbohydrate metabolism:

In an absorptive state, glucose is the only

fuel source to the brain.

About 120 g of glucose is utilized per day.

50% of the energy is utilized by plasma

membrane Na+ - K+ ATPase for nerve

impulse transmission.

Lipid metabolism:

The free fatty acids cannot cross the blood-

brain barrier, hence their contribution to the

brain is insignificant.

In a fed state, ketone bodies are almost

negligible as fuel source to the brain.

Brain predominantly depends on ketone

bodies during prolonged starvation.

Metabolic integration in well fed state

Liver in starvation:

Carbohydrate metabolism:

Liver is to act as a blood glucose buffering

organ.

During starvation, increased

gluconeogenesis & elevated glycogen

degradation furnish glucose to the needy

tissues (mostly brain).

Lipid metabolism:

Fatty acid oxidation is increased with an

elevated synthesis of ketone bodies.

This is due to TCA cycle cannot cope up with

the excess production of acetyl CoA & it is

diverted for ketone body synthesis.

The brain slowly adapts itself to use ketone

bodies.

Metabolic integration in Starvation

Adipose tissue in starvation:

Carbohydrate metabolism:

Glucose uptake & its metabolism are lowered.

Lipid metabolism:

The degradation of TAG is elevated &

increased release of fatty acids which serve as

fuel source (brain is an exception).

Glycerol is precursor for glucose.

Synthesis of fatty acids & TAG is stopped.

Skeletal muscle in starvation:

Carbohydrate metabolism:

Glucose uptake & its metabolism are depressed.

Lipid metabolism:

Fatty acids & ketone bodies are utilized by

muscle.

On prolonged starvation, muscle adapts to

exclusively utilize fatty acids.

This increases the ketone bodies in circulation.

Protein metabolism:

During the early period of starvation, muscle

proteins are degraded to liberate the amino

acids which are effectively utilized by the

liver for glucose synthesis (gluconeogenesis).

On prolonged starvation, however, protein

breakdown is reduced.

Brain in starvation:

The brain is mostly dependent on glucose.

This, in turn, is dependent on the amino acids

released from the muscle protein degradation.

Starvation beyond 3 weeks, results in increase

in ketone bodies.

The brain adapts itself to depend on ketone

bodies for the energy needs.

Textbook of Biochemistry-U Satyanarayana

Textbook of Biochemistry-DM Vasudevan