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Ketogenesis
Jul 17, 2024
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Ketogenesis Lecture Notes
Overview
Ketogenesis
: Process occurring when there's an excess of acetyl-CoA but not enough oxaloacetate.
Trigger
: Largely due to a lack of oxaloacetate, which prevents acetyl-CoA from entering the citric acid cycle.
Causes of Excess Acetyl-CoA
Diabetes
: Body cannot uptake glucose, leading to perceived starvation.
Glycogen stores are depleted.
Body switches to burning fatty acids.
Starvation
: Similar pathway as diabetes.
Low glucose intake depletes glycogen, necessitating fatty acid burning.
Normal Fasting
: Even healthy individuals can undergo ketogenesis during fasts or overnight.
Pathway of Ketogenesis
Two molecules of acetyl-CoA
combine through a series of steps.
End Products
: Acetone and beta-hydroxybutyrate.
Clinical Indicators
Acetone Detection
: Can be smelled on breath or found in urine of individuals undergoing ketogenesis.
Ketone Bodies
: Specifically look for acetone and beta-hydroxybutyrate in clinical tests.
Diabetic Tests
: Amount of ketone bodies/acetone in urine is monitored.
Uses and Metabolism of Beta-Hydroxybutyrate
Energy Source
: Exported from liver to other tissues, especially the brain.
Brain Priority
: Brain uses beta-hydroxybutyrate as it is energy-efficient.
In diabetics, causes tingling in extremities as energy is diverted to the brain.
Conversion Steps
:
Beta-hydroxybutyrate is reduced to generate NADH.
Converted to acetoacetate.
Acetoacetate undergoes transferase reaction, accepting a CoA group to form acetoacetyl-CoA.
Acetoacetyl-CoA yields two molecules of acetyl-CoA via thiolase reaction.
Citric Acid Cycle Under Starvation
Limited Oxaloacetate
: Only the essential oxaloacetate is used for citric acid cycle.
Body Preserving Brain
: All processes that could divert molecules from the cycle are shut down.
ATP Generation
: Each acetyl-CoA through the citric acid cycle produces around 10 ATP.
Summary
Ketogenesis
: Formation of acetone and beta-hydroxybutyrate is a response to excess acetyl-CoA & low oxaloacetate.
Normal in fasting, but also a clinical marker in diabetes.
Energy Management
: Body prioritizes brain energy needs during perceived starvation, limiting ketone bodies to other tissues.
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