glucose metabolism of various vital organ and biochemical phenomenon

1. ORGAN SPECIALIZATION IN
FUEL METABOLISM
SABAPATHI. N

2. ORGAN SPECIALIZATION in fuel metabolism
• Different organs have different metabolic functions and
capabilities.
• Brain,
• Muscle,
• Liver,
• Adipose tissue and
• Kidney

3. The metabolic interrelationships among brain, adipose tissue, muscle, liver, and
kidney.

4. Brain
• Brain tissue has a remarkably high respiration rate
• consumption,- moreover independent of the state of mental
activity
• Most of the brain’s energy production serves to power the
plasma membrane (Na+–K+)–ATPase which maintains the
membrane potential required for nerve impulse
transmission .
2% of the adult
body mass
But responsible
20% of its
resting O2
consumption.

5. • The electrochemical potential gradient generated by the
(Na+–K+) pump is responsible for the electrical excitability
of nerve cells
Kinetic scheme for the active transport of Na and K by (Na–K)–ATPase.

6. • Glucose serves as the brain’s only fuel
(although, with extended fasting, the brain gradually
switches to ketone bodies)
• Brain cells store very little glycogen
• They require a steady supply of glucose from the blood.
• A blood glucose concentration of less than half of the
normal value of ~5 mM results in brain dysfunction.

7. MUSCLE
• Muscle’s major fuels are glucose from glycogen, fatty
acids, and ketone bodies.
• Glycogen -1 to 2% of its mass.
• Glycogen readily available fuel depot
glycogen
G6P

8. • Alanine is then exported via the bloodstream to the liver
• Transaminates it back to pyruvate, a glucose precursor.
This process is known as the glucose–alanine cycle
In Fasting state Muscle serves the body as
Energy reservoir because
proteins are
degraded to amino
acids
Alanine converted to pyruvate
Transamination

9. • Does not participate in gluconeogenesis, it lacks the
machinery that regulates
• Muscle does not have receptors for glucagon
• Muscle possesses epinephrine receptors( 𝝱-adrenergic
receptors)
• The intermediacy of cAMP control the phosphorylation/
Dephosphorylation cascade system that regulates
glycogen breakdown and synthesis

10. Muscle Contraction Is Anaerobic Under
Conditions of High Exertion
• Muscle contraction is driven by ATP hydrolysis and is
therefore ultimately dependent on respiration.
• Skeletal muscle at rest utilizes ~30% of the O2 consumed
by the human body.

11. Muscle Fatigue Has a Protective Function
Muscle fatigue, defined as the inability of a muscle to
maintain a given power output,
occurs in 20 s under conditions of maximum exertion
[fatigue is not caused by the exhaustion of the muscle’s
glycogen supply]
• Result from glycolytic proton generation that can drop the
intramuscular pH from its resting value of 7.0 to as low
as 6.4

12. • Fatigue does not, result from the buildup of lactate itself,
As is demonstrated by the observation
- muscles can sustain a large power output under
high lactate concentrations if the pH is maintained near 7.0
• How acidification might cause muscle fatigue?- unclear.
Two other proposed causes for m. fatigue
• 1. the increased [Pi] arising largely from the utilization of
ATP may precipitate Ca2
+ as calcium phosphate (which is
highly insoluble), thereby decreasing
• contractile force (muscle contraction is triggered by the
release of Ca2
+ ion

13. 2. The K+ ion known to be released from contracting
muscle cells
• Result in their depolarization and hence a reduction in
their contraction.

14. The Heart Is a Largely Aerobic Organ
• Entirely on aerobic metabolism
• Richly endowed with mitochondria; they comprise up to
40% of its cytoplasmic space,
• The heart can metabolize fatty acids, ketone bodies,
glucose, pyruvate,and lactate.
• Fatty acids - resting heart’s fuel of choice
• Heavy workload - consumption of glucose increased

15. Liver
• liver is the body’s central metabolic clearinghouse
• major functions is to act as a blood glucose “buffer.”
Releasing Glucose In
Response
levels of
• Glucagon,
• Epinephrine,
• Insulin and
• Concentration of glucose
itself

16. Glucokinase
• Lower affinity for glucose
• Reaches half-maximal velocity at ~5 mM glucose vs ~0.1
mM glucose for hexokinase
• Not inhibited by G6P.
After a carbohydrate-containing meal,
Blood glucose concentration reaches 6 mm,
Glucose G6P
Glucokinase
In liver

17. The Fate of Glucose-6-Phosphate Varies with Metabolic
Requirements
Glucose-6-Phosphate
To glucose by
action of G6Pase
TO GLYCOGEN TO ACETYL COA
HMP shunt
(NADPH generated )

18. The Liver Can Synthesize or Degrade
Triacylglycerols
1. Demand for metabolic fuels is high
- Fatty acids are degraded to acetyl-CoA and then to
ketone bodies for export via the bloodstream to the
peripheral tissues.
2. Demand for metabolic fuels is low
• Fattyacids are used to synthesize triacylglycerols that are
secreted into the bloodstream as VLDL for uptake by
adipose tissue.

19. Amino Acids Are Important Metabolic Fuels
• Degrades amino acids to a variety of metabolic
intermediates
• The liver’s glycogen store is insufficient to supply the
body’s glucose needs for more than ~6 hrs after a meal.
• After that, glucose is supplied through gluconeogenesis
from amino acids arising mostly from muscle protein
degradation(alanine, glutamine)

20. The Liver Is the Body’s Major Metabolic Processing Unit
• The synthesis of blood plasma proteins,
• The degradation of porphyrins and nucleic acid bases
• The storage of iron, and
• The detoxification of biologically active substances such as
drugs, poisons, and hormones by a variety of oxidation
(e.g., By cytochromes P450), reduction, hydrolysis,
conjugation, and methylation reactions.