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KETOGENESIS
Ketogenesis is the process
by which KETONE BODIES or
compounds are produced
from acetyl CoA molecules as
a result of fatty acid
degradation.
KETOGENESIS
 Ketone bodies are produced mainly in the
mitochondria of hepatocytes.
 Its synthesis occurs in response to low
glucose levels in the blood, and after
exhaustion of cellular carbohydrate stores,
such as glycogen.
 The production of ketone bodies is then
initiated to make available energy that is
stored as fatty acids.
KETOGENESIS
 However, if the amounts of acetyl-CoA
generated in fatty-acid β-oxidation
challenge the processing capacity of the
TCA cycle or if activity in theTCA cycle is
low due to low amounts of intermediates
such as oxaloacetate, acetyl-CoA is then
used instead in biosynthesis of ketone
bodies via acetoacyl-CoA and β-hydroxy-
β-methylglutaryl-CoA (HMG-CoA).
KETOGENESIS
REVIEW!
 Fatty acids undergo β-
oxidation to form
acetyl-CoA.
 Normally, acetyl-CoA is
further oxidized and its
energy transferred as
electrons to NADH,
FADH2, and GTP in the
Krebs cycle.
KETOGENESIS
KETOGENESIS
 The three ketone bodies are:
 Acetoacetate - if not oxidized to form usable
energy, it is the source of the two other ketone
bodies below.
 Acetone - is not used as an energy source, but is
instead exhaled or excreted as waste.
 β-hydroxybutyrate - it is not technically a ketone
according to IUPAC nomenclature.
 Each of these compounds are synthesized from acetyl-
CoA molecules.
KETOGENESIS
 Ketogenesis may or may not occur,
depending on levels of available
carbohydrates in the cell or body.
 When the body has ample carbohydrates available
as energy source, glucose is completely oxidized
to CO2.
 When the body has excess carbohydrates
available, some glucose is fully metabolized, and
some of it is stored by using acetyl-CoA to create
fatty acids.
KETOGENESIS
 When the body has no free carbohydrates
available, fat must be broken down into acetyl-
CoA in order to get energy. Acetyl-CoA is not
being recycled through the citric acid cycle
because the citric acid cycle intermediates (mainly
oxaloacetate) have been depleted to feed the
gluconeogenesis pathway, and the resulting
accumulation of acetyl-CoA activates ketogenesis.
 Ketogenesis provides energy for vital organs’
functions during prolonged starvation
KETOGENESIS
KETOGENESIS
KETOGENESIS
 Ketone bodies are created at moderate levels
in our bodies, such as during sleep and other
times when no carbohydrates are readily
available.
 However, when ketogenesis is happening at
higher than normal levels, the body is said to
be in a state of ketosis. Ketone bodies
accumulation in the body may result to
negative long term effects.
KETOGENESIS
 Abnormally high concentration of ketone
bodies in the body results in the decrease of
pH level of the blood.This state is called
ketoacidosis.
 Ketoacidosis is very rare to occur. It is,
however, more seen in people suffering from
untreated Diabetes mellitus (DM) and in
those alcoholics after binge drinking and
subsequent starvation.
KETOGENESIS
 Abnormally high concentration of ketone
bodies in the body results in the decrease of
pH level of the blood.This state is called
ketoacidosis.
 Ketoacidosis is very rare to occur. It is,
however, more seen in people suffering from
untreated Diabetes mellitus (DM) and in
those alcoholics after binge drinking and
subsequent starvation.
Diabetes and Ketoacidosis
 When there is not enough insulin in the blood,
glucose is not used efficiently to produce energy.
Thus, the body must break down lipids for its
energy.
 Lipid degradation leads to ketones build up in
the blood. Ketone then spill over into the urine
so that the body can get rid of them. Acetone
can be exhaled through the lungs.This gives the
breath a fruity odor. Ketones that build up in the
body for a long time lead to serious illness and
coma. (Diabetic ketoacidosis)

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21190_Ketogenesis.ppt

  • 1. KETOGENESIS Ketogenesis is the process by which KETONE BODIES or compounds are produced from acetyl CoA molecules as a result of fatty acid degradation.
  • 2. KETOGENESIS  Ketone bodies are produced mainly in the mitochondria of hepatocytes.  Its synthesis occurs in response to low glucose levels in the blood, and after exhaustion of cellular carbohydrate stores, such as glycogen.  The production of ketone bodies is then initiated to make available energy that is stored as fatty acids.
  • 3. KETOGENESIS  However, if the amounts of acetyl-CoA generated in fatty-acid β-oxidation challenge the processing capacity of the TCA cycle or if activity in theTCA cycle is low due to low amounts of intermediates such as oxaloacetate, acetyl-CoA is then used instead in biosynthesis of ketone bodies via acetoacyl-CoA and β-hydroxy- β-methylglutaryl-CoA (HMG-CoA).
  • 4. KETOGENESIS REVIEW!  Fatty acids undergo β- oxidation to form acetyl-CoA.  Normally, acetyl-CoA is further oxidized and its energy transferred as electrons to NADH, FADH2, and GTP in the Krebs cycle.
  • 6. KETOGENESIS  The three ketone bodies are:  Acetoacetate - if not oxidized to form usable energy, it is the source of the two other ketone bodies below.  Acetone - is not used as an energy source, but is instead exhaled or excreted as waste.  β-hydroxybutyrate - it is not technically a ketone according to IUPAC nomenclature.  Each of these compounds are synthesized from acetyl- CoA molecules.
  • 7. KETOGENESIS  Ketogenesis may or may not occur, depending on levels of available carbohydrates in the cell or body.  When the body has ample carbohydrates available as energy source, glucose is completely oxidized to CO2.  When the body has excess carbohydrates available, some glucose is fully metabolized, and some of it is stored by using acetyl-CoA to create fatty acids.
  • 8. KETOGENESIS  When the body has no free carbohydrates available, fat must be broken down into acetyl- CoA in order to get energy. Acetyl-CoA is not being recycled through the citric acid cycle because the citric acid cycle intermediates (mainly oxaloacetate) have been depleted to feed the gluconeogenesis pathway, and the resulting accumulation of acetyl-CoA activates ketogenesis.  Ketogenesis provides energy for vital organs’ functions during prolonged starvation
  • 11. KETOGENESIS  Ketone bodies are created at moderate levels in our bodies, such as during sleep and other times when no carbohydrates are readily available.  However, when ketogenesis is happening at higher than normal levels, the body is said to be in a state of ketosis. Ketone bodies accumulation in the body may result to negative long term effects.
  • 12. KETOGENESIS  Abnormally high concentration of ketone bodies in the body results in the decrease of pH level of the blood.This state is called ketoacidosis.  Ketoacidosis is very rare to occur. It is, however, more seen in people suffering from untreated Diabetes mellitus (DM) and in those alcoholics after binge drinking and subsequent starvation.
  • 13. KETOGENESIS  Abnormally high concentration of ketone bodies in the body results in the decrease of pH level of the blood.This state is called ketoacidosis.  Ketoacidosis is very rare to occur. It is, however, more seen in people suffering from untreated Diabetes mellitus (DM) and in those alcoholics after binge drinking and subsequent starvation.
  • 14. Diabetes and Ketoacidosis  When there is not enough insulin in the blood, glucose is not used efficiently to produce energy. Thus, the body must break down lipids for its energy.  Lipid degradation leads to ketones build up in the blood. Ketone then spill over into the urine so that the body can get rid of them. Acetone can be exhaled through the lungs.This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. (Diabetic ketoacidosis)