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Summary of ketone metabolism. (Biochemistry)
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This document provides a simple illustration of ketone bodies metabolism in human body. It’s easy to comprehend and good for pre-test review.
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Ketone Metabolism I CitrateThe ketone metabolism is not a preferable source of energy in the body. However, it's utilized in certain
conditions: low Glucose in the blood, prolonged starvation, and diabetic condition (uncontrolled diabetes
mellitus type 1).
TCA 2
I
The ketone bodies are mainly synthesized in the liver. But the lysis, the breakdown of ketone bodies,
AA
primarily happens in the brain and muscles.
I jetyteon
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Carbs are the main source of energy in the body. So, a deficiency of Glucose in the body will result in a I
low concentration of pyruvate and Acetyl-CoA. This will affect the Krebs cycle and lead to a lower ATP
concentration. I t
Gluconeogenesis
However, the body will shift to the 2nd source of fuel, Fatty acids. FA will enter Beta-Oxidation to form
more Acetyl CoA and generate ATP's. But the problem is that Acetyl CoA can't combine with OAA and I p jp
begin the Krebs cycle because a lot of OAA enters Gluconeogenesis and converts into Glucose to
compensate for the acute shortage of Glucose. PY
So, there will be an accumulation of Acetyl-CoA.
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Let's now talk about Ketone bodies synthesis.
Glucose
Giger
Firstly, two molecules of Acetyl-CoA will combine, catalyzed by the Acetyl-CoA Acyl Transferase
enzyme. And they are popping out one CoA. So the new molecule is called (Aceto-Acetyl CoA).
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Another Acetyl-CoA will combine with Aceto-Acetyl CoA and pop out one CoA. This reaction will be
catalyzed by a rate-limiting enzyme (HMG-CoA Synthase).
Forming a new molecule called (3-OH-3-methyl gluteryl-CoA/ HMG-CoA).
HMG-CoA will react with (HMG-CoA lyase) enzyme and pop out Acetyl-CoA. The new molecule is going to
be referred to as (Aceto-acetate). This molecule is one of the ketone bodies and can get put directly
into the blood. 1st stice FA
But some of these Aceto-acetate will be converted into another model of another ketone body. For
example, beta-OH-Butyrate dehydrogenase enzyme will catalyze this molecule and convert it into (B-
OH-Butyrate). So this molecule is another ketone that can also get put directly into the blood.
often 2845 T
Another enzyme that will convert Aceto-acetate into Aceto-acetate Decarboxylase. It will rip off one
carbon molecule and convert it into (Acetone). Acetone is a very dangerous molecule in the body.
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In certain people who have uncontrolled diabetes mellitus type 1 and having a lot of ketone metabolism,
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one of the diagnostic tools is to smell their breath. Because they're going to be having a lot of acetones
that are going to try to breathe off, and these people will have a fruity breath.
Aceto-acetate and B-Hydroxy Butyrate are very acidic, making the blood in our body very acidic and Thiophphor
I
leading to acidosis. Also, when an excessive amount of these molecules stimulate the chemo trigger zone
on the area postrema of the brainstem, which leads to vomiting a lot of fluid and causes hypovolemia.
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