What is Ketosis

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What is Ketosis?
An excessive production of ketones in the
blood 3 derivatives of acetyl-CoA
Acetoacetate
??-hydroxybutyrate
Acetone
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What is the Significance of ketosis
Acidosis
Excessive acid in the blood
Overflow
Excessive oxidation of fatty acids
Metabolic Problem
Faulty Carbohydrate Metabolism
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Metabolic fate of Acetyl CoA
Pyruvate
minor
Acetyl-CoA
Fatty Acids
Ketone Bodies
major
Citrate
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HS-CoA
CH3C

?-Ketothiolase
rearrangement
OH
Acetoacetyl-CoA
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HMG-CoA Synthase
?-hydroxy-?-methyl glutaryl-CoA
(HMG-CoA)
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HMG-CoA
HMG-CoA Lyase

Acetone
?-hydroxybutyrate
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Diabetes
Insufficient insulin production (Type I)
Ineffective or impaired insulin function (Type
II)
Main Characteristics
Failure to transport glucose into muscle and
adipose tissue
Failure to catabolize glucose at a normal rate in
liver
Excessive oxidation of fatty acids leading
to ketosis
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Diabetes and Lipid Metabolism
Whenever carbohydrates are not available
for metabolism, fatty acid oxidation is
accelerated
A more rapid degradation of fatty acids augments
production of acetoacetyl-CoA and acetyl CoA
OAA is being used for gluconeogenesis
Less carbohydrate means less pyruvate. Less
pyruvate means less OAA. Less OAA means less
citrate
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INSULIN
Pancreas beta cells
5.8 kDa polypeptide
Emulates the fed signal
Lowers blood glucose
Stimulates glycogen synthesis
Stimulates glycolysis
NO BACKUP
Stimulates lipid synthesis
Suppresses Glucagon
GLUCAGON
Pancreas alpha cells
3.5 kDa polypeptide
Emulates the need signal
Raises blood glucose
Stimulates glycogen breakdown
Stimulates gluconeogenesis
GLUCORTICOIDS BACKUP
Stimulates lipolysis
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ADIPOSE TISSUE
Glucose
Triacylglycerols
No glucose uptake by adipose
3 fatty acids
Glucagon-stimulated lipase
Glycerol-PO4
DHAP
Glycerol kinase
3 Fatty acids
Glycerol
Missing in adipose tissue
Blood
Breakdown of adipose lipids grossly accelerated
Liver
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LIVER
FA
Glucose
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
Pyruvate
Ketone bodies
OAA
CITRATE
Glucose
All glucagon-stimulated activities take precedence