1. By
Dr. Inayat ur Rahman Abbasi
MBBS, M.Phil Biochemistry
Associate Professor of Biochemistry
Azad Jammu & Kashmir Medical
College Muzaffarabad

2.  There are three important compounds in the body
which are collectively called ketone bodies or
acetone bodies or incorrectly ketones,
 Because all ketones are not KB and all KB are not
chemically ketones.
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3.  These are Aceto-acetate (primary KB), Acetone &
β-Hydroxy Butyrate (secondary KB).
 Ketogenesis starts from mitochondrial Acetyl CoA
in Liver, synthesis is mainly hepatic in nature but
liver due to absence of enzyme thiophrase or
Aceto-acety CoA transferase is unable to utilized
KB as source of energy.
 So KB’s synthesis is hepatic but their utilization is
extra-hepatic in nature.
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4.  These are the source of energy (when needed)
especially for cardiac, skeletal muscles, brain
and adrenal cortex.
 These are soluble in aquous solution, so in
plasma these are transported as such and do not
required any lipoproteins.
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5.  Ketogenesis and their utilization is
taking place even in normal
conditions but both process occur at
slow level in such a way that their
normal level remains <1.0 mg/dl.
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6.  KB concentration when increased in body
indicates:
 Excessive production acetyl CoA (increased
Lipolysis) or
 Depressed utilization of acetyl CoA by TCA-Cycle.
 Main causes are uncontrolled Diabetes,
starvation, prolonged fasting, excessive diarrhea/
vomiting.
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7.  Ketone bodies (being an acid) when increased in
plasma, liberate H+ ions, which are buffered by
HCO3-/H2CO3 buffere system. But if their
production is high, buffer will fail leading to high
concentration of H+ ion or decrease pH of plasma
causing metabolic Acidosis.
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8.  Aceto-acetate is first to form called Primary KB
while other KB are formed from it & are called
Secondary KB.
 Acetone is the only volatile KB that can be expired
through lungs, giving typical smell in breath;
especially seen in uncontrolled Diabetes or DKA.
While β-OH-butyrate is the KB that is found in
highest conc. in blood. Ketosis is the combination
of ketonaemia & ketonuria
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9.  Two molecules of Acetyl CoA are condensed to
form Aceto-acetyl CoA by Aceto-acetyl CoA
synthase enzyme, to that one more molecule of
Acetyl CoA is added to form HMG-CoA by HMG-
CoA synthase enzyme.
 This is a rate limiting step of ketogenesis,
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10.  upto HMG-CoA production keto-
genesis and cholesterol synthesis
both share the same steps,
 after that two cycles have difference,
 cytocolic HMG-CoA reduced to form
cholesterol
 while mitochondrial HMG-CoA is
lysed to form ketone bodies.
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11.  Finally HMG-CoA (a 6-carbon compound) is lysed
to form first primary KB called Aceto-acetate,
 this KB is not only form from Acetyl-CoA but can
also be form from degredation of carbon skeleton
of some ketogenic amino acids like Isoleu, leu,
Phe, Lys, Tyr etc.
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12.  Once aceto-acetate is formed it can give rise to
two other KB called secondary KB.
 Aceto-acetate can be spontenously
decarboxylated (without any enzyme) to form
Acetone
 or it can be dehydrogenated by NADH-dependant
dehydrogenase to form β-OH-butyrate.
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13.  2 x Acetyl CoA (2C)
 ↓ Synthase
 Aceto-acetyl CoA (4C) + Acetyl CoA
(2C)
 ↓ Synthase
 HMG- CoA (6C)
 ↓ Lyase
 Aceto-Acetate + Acetyl CoA
 Decarboxylase↓Dehydrogenase
 Acetone (3C) OR β-OH-butyrate (4C)
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14.  Ketosis when present shows excessive lipolysis in
the body or excessive burn of body fats to provide
energy in body.
 Signs & symptoms are increase urination,
vomiting, dehydration and coma.
 While laboratory findings are increased KB in
blood, increased H+ or ↓pH of blood, increased
urinary KB and Na+ excretion.
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