Download What is Ketosis

What is Ketosis?
An excessive production of ketones in the blood
3 derivatives of acetyl-CoA
Acetoacetate
-hydroxybutyrate
Acetone
CH3CCH2COOO

H
CH3CCH2COOOH
O
CH3-C-CH3
What is the Significance of
ketosis
Acidosis
Excessive acid in the blood
Overflow
Excessive oxidation of fatty acids
Metabolic Problem
Faulty Carbohydrate Metabolism
Metabolic fate of Acetyl CoA
Pyruvate
minor
Fatty Acids
Acetyl-CoA
major
Citrate
Ketone Bodies
CH3C~SCoA
O
CH3C~SCoA
O
HS-CoA
CH2C~SCoA
CH3C + O
rearrangement
OH
-Ketothiolase
CH3CCH2C~SCoA
O
O
Acetoacetyl-CoA
CH3CCH2C~SCoA
O
O
HS-CoA
CH3C~SCoA
O
CH2C-OO
CH3CCH2C~SCoA
HO
O
OH
OOC-CH2-C-CH2-C~SCoA
CH3
O
HMG-CoA
Synthase
-hydroxy--methyl
glutaryl-CoA
(HMG-CoA)
OH
OOC-CH2-C-CH2-C~SCoA
HMG-CoA
Acetoacetate
CH3
O
CH3-C~SCoA
O
OH
+ 2-C~SCoA HMG-CoA
OOC-CH2-C-CH
Lyase
CH3 O
OOC-CH2-C-CH3
O
CO2
NADH + H+
NAD+
CH3-C-CH3
OOC-CH2-CH-CH3
O
Acetone
OH
-hydroxybutyrate
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
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
INSULIN
Pancreas beta cells
5.8 kDa polypeptide
Emulates the fed signal Lowers blood glucose
Stimulates glycogen synthesis
Stimulates glycolysis
Stimulates lipid synthesis
NO BACKUP
Suppresses Glucagon
GLUCAGON
Pancreas alpha cells
3.5 kDa polypeptide
Emulates the “need” signal Raises blood glucose
Stimulates glycogen breakdown
Stimulates gluconeogenesis
GLUCORTICOIDS
Stimulates lipolysis
BACKUP
ADIPOSE TISSUE
Triacylglycerols
Glucagon-stimulated
lipase
Glucose
No glucose
uptake by
3 fatty acids
adipose
Glycerol-PO4
DHAP
3 Fatty acids + Glycerol
Glycerol kinase
Missing in
adipose tissue
Blood
Liver
Breakdown of adipose lipids
grossly accelerated
FA
Glucose
Pyruvate
LIVER
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
CO2
Ketone bodies
OAA
CITRATE
Glucose
All glucagon-stimulated activities take precedence