Question

The processes for ketone body formation and consumption as an alternative fuel.

• What metabolic conditions promote ketone body formation?

• Describe the reactions that convert acetyl-CoA to acetoacetate and β-

  hydroxybutryate. Be able to recognize the intermediates in this pathway.

• Describe how β-hydroxybutyrate is converted to acetyl-CoA in non-liver

  peripheral tissues.

• Describe the condition known as ketoacidosis. Why is it potentially life-

  threatening?

Answer 1

Ketone bodies are a group of three ketone conrtaining molecules namely, acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone. The maybe called ketone bodies. These are water soluble molecules. Such ketone bodies are produced by the liver from fatty acids during situations of low food intake or fasting or food intake with low carbohydrates and also starvation.

Metabolic conditions promoting ketone body formation:

Ketone bodies are produced from acetyl-CoA in the liver when carbohydrates are so scarce that energy must be obtained from breaking down of fatty acids. This state is called ketosis. Without insulin to extract the glucose from the blood, tissues the levels of malonyl-CoA are reduced, and it becomes easier for fatty acids to be transported into mitochondria, this causes the accumulation of excess acetyl-CoA. The accumulation of acetyl-CoA in turn produces excess ketone bodies through ketogenesis.

β-hydroxybutyrate is converted to acetyl-CoA in non-liver

peripheral tissues whein it NAD is added causing it to form to acetoacetate. Addition of succinyl CoA produces acetoacetyl CoA. This product upon ketosis produce Acetyl CoA.

Diabetic ketoacidosis

It is a serious complication of diabetes that occurs when your body produces high levels of blood acids called ketones. The condition develops when your body can't produce enough insulin. Sugar is a main source of energy for the cells. Normally, insulin helps sugar enter your cells. Without insulin, body can't use sugar properly for. This release hormones that break down fat as fuel, which produces acids known as ketones. Excess ketones build up in the blood and eventually "spill over" into the urine.

The risk of diabetic ketoacidosis is highest if you have type 1 diabetes and you frequently miss insulin doses.

The reactions:

The ketone bodies produced are energy rich molecules that transfer energy between liver and body tissues. Ketogenesis is the process through which ketone bodies are formed.

Processes for ketone body formation: