Ketogenesis Flashcards by John Fasulo

Q

When will Ketone Body Synthesis typically occur?

A

When Glycogenolysis & Gluconeogenesis substrates are exhausted (starvation)

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Q

Once Acetyl CoA is produced through Fatty Acid Oxidation, what two pathway’s can it be utilized for?

A

Ketone Bodies or TCA Cycle

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Q

What is the first step of Ketone Body Synthesis?

A

x2 Acetyl CoA’s combine to form Acetylacetyl CoA

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Q

What is the enzyme that catalyzes the reaction of combining x2 Acetyl CoA’s to form Acetylacetyl CoA?

A

Thiolase

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Q

What is the 2nd step of Ketone Body Synthesis?

A

Acetylacetyl CoA converts to HMG-CoA

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Q

What is the enzyme that converts Acetylacetyl CoA into HMG-CoA?

A

HMG-CoA Synthase

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Q

What is unique about the 2nd step of Ketone Body Synthesis?

A

A 3rd Acetyl CoA Molecule is added to Acetylacetyl CoA to make HMG-CoA

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Q

What is the 3rd step of Ketone Body Synthesis?

A

HMG-CoA is converted into Acetoacetate

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Q

What is the enzyme that converts HMG-CoA into Acetoacetate?

A

HMG-CoA Lyase

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Q

What is unique about step 3 of Ketone Body Synthesis?

A

An Acetyl CoA molecule is produced as a byproduct (essentially recycling the molecule)

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Q

What is the first ketone that is produced in ketone body synthesis?

A

Acetoacetate

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Q

Once the first ketone is formed in ketone body synthesis, how many pathway options are available for further conversions?

A

2 pathway options

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Q

What is step 4(A) of Ketone Body Synthesis?

A

Acetoacetate is converted into Acetone

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Q

What is the enzyme that converts Acetoacetate into Acetone?

A

Acetoacetate Decarboxlyase

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Q

What is a byproduct of step 4A of Ketone Body Synthesis?

A

CO2

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Q

What is step 4(B) of Ketone Body Synthesis?

A

Acetoacetate is converted into Beta-Hydroxybutyrate

Q

What is the enzyme that converts Acetoacetate to Beta-Hydroxybutyrate?

A

Beta-Hydroxybutyrate Dehydrogenase

Q

What are 3 ketones produced from Ketone Body Synthesis?

A

Acetoacetate, Acetone & Beta-Hydroxybutyrate

Q

What is the first condition in which the body will want to form Ketones?

A

Starvation

Q

In Starvation states what molecule is depleted preventing other energy pathways from producing fuel?

A

Oxaloacetate

Q

How is Oxaloacetate depleted over time?

A

Reoccurring cycles of gluconeogenesis

Q

In Starvation states, why can’t the TCA Cycle produce fuel?

A

Oxaloacetate is depleted from reoccurring cycles of gluconeogenesis

Q

What identical pathophysiology occurs in starvation states but is a diabetic condition?

A

Diabetic Ketoacidosis

Q

In Diabetic Ketoacidosis, if Hyperglycemia is high what is the status of Insulin & Glucagon?

A

Low Insulin (Type 1 Diabetic)
High Glucagon (b/c of low Insulin)

If insulin is low, what metabolic pathway cannot function?

Glycolysis

If Glucagon is high, what metabolic pathway is running?

Gluconeogenesis

When is Ketone Synthesis Used?

1.) Prolonged Starvation 2.) Diabetic Ketoacidosis 3.) Alcoholism

How is Alcohol (Ethanol) Metabolized?

Ethanol > Acetaldehyde > Acetate

What are the byproducts of converting Ethanol to Acetaldehyde?

NAD+ / NADH

In chronic alcohol consumption (increased ethanol) what effect to alcohol metabolism byproducts is observed?

Decreased NAD+ Increased NADH

Why is decreased NAD+ & Increased NADH an issue for oxidative metabolism?

To form oxaloacetate (for use in the TCA cycle) NAD+ is needed to convert to NADH to form oxaloacetate. No NAD+ , No Oxaloacetate , No Gluconeogenisis (or) TCA Cycle

What is a good way to remember how/why ketones are produced in alcoholism?

"NAD+-y Light"

What is the rate-limiting enzyme of Ketone Body Synthesis?

HMG-CoA Synthase

People in Ketosis, often have "fruity" breath. What is the cause of this?

The Acetone concentrations