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CoA levels increase to high levels, they are condensed into acetoacetic acid which can further

be converted to beta-hydroxybutyrate and acetone, the three major ketone bodies.

Figure 2: Interrelationship between Malonyl-CoA and CPT-1

Glycogen Malonyl CoA

(inhibits)

CPT-1

(stimulates)

FFA Acetyl-CoA Acetoacetate Acetone

Krebs Cycle Beta-hydroxybutyrate

Section 3: Ketosis and Ketoacidosis

Having discussed the mechanisms behind ketone body production, we can now examine
the metabolic state of ketosis, and what it represents. Additionally, ketosis is contrasted to
runaway diabetic ketoacidosis.

What is ketosis?

Ketosis is the end result of a shift in the insulin/glucagon ratio and indicates an overall shift
from a glucose based metabolism to a fat based metabolism. Ketosis occurs in a number of
physiological states including fasting (called starvation ketosis), the consumption of a high fat
diet (called dietary ketosis), and immediately after exercise (called post-exercise ketosis). Two
pathological and potentially fatal metabolic states during which ketosis occurs are diabetic
ketoacidosis and alcoholic ketoacidosis.

The major difference between starvation, dietary and diabetic/alcoholic ketoacidosis is in
the level of ketone concentrations seen in the blood. Starvation and dietary ketosis will normally
not progress to dangerous levels, due to various feedback loops which are present in the body
(12). Diabetic and alcoholic ketoacidosis are both potentially fatal conditions (12).

All ketotic states ultimately occur for the same reasons. The first is a reduction of the
hormone insulin and an increase in the hormone glucagon both of which are dependent on the
depletion of liver glycogen. The second is an increase in FFA availability to the liver, either from
dietary fat or the release of stored bodyfat.

Under normal conditions, ketone bodies are present in the bloodstream in minute amounts,
approximately 0.1 mmol/dl (1,6). When ketone body formation increases in the liver, ketones
begin to accumulate in the bloodstream. Ketosis is defined clinically as a ketone concentration
above 0.2 mmol/dl (6). Mild ketosis, around 2 mmol, also occurs following aerobic exercise. (4).
The impact of exercise on ketosis is discussed in chapter 21.