Ketone Bodies

• When there is a adequate balance bet. Lipid and carbohydrate metabolism, most of the acetyl CoA produced from the B-oxidation pathway is further processed through the citric acid cycle.

• The first step of the citric acid cycle involves the reaction between oxaloacetate and acetyl CoA. Sufficient oxaloacetate must be present for the acetyl CoA to react with.

• Certain body conditions upset the lipid-carbohydrate balance required for acetyl CoA generated by fatty acids to be processed by the citric acid cycle. These condition include

dietary intake high in fat and low in carbohydratesDiabetic condition where the body cannot adequately

processed glucose even though it is presentProlonged fasting condition, including starvation, where

glycogen supplies are exhausted.

Under these conditions, the problem of adequate oxaloacetate supplies arises, which is compounded by the body’s using oxaloacetate that is present to produce glucose through gluconeogenesis.

• Ketone body is one of the three substances ( acetoacetate, B- hydroxybutyrate and acetone) produced from acetyl CoA when an excess of acetyl CoA from fatty acid dergadation accumulates because of triacylglycerol- carbohydrate metabolic Imbalances. The structural formulas for the three ketone bodies, two of which are C4 molecules and the other a C3 molecule.

• Ketogenesis

`is the metabolic pathway by which ketone bodies are snythesize from acetyl CoA. Items to consider about this process prior to looking at the actual steps in this four step process are:

• 1. the primary site for the process is liver mitochondria.

• 2. the first keyone body to be produced is acetoacetate. This production occurs in step 3 of ketogenesis.

• 3. some of these acetoacetate produced in step 3 is converted to the second ketone body, B- hydroxybuterate. In step 4 of ketogenesis.

• 4. the acetoacetate and B-hydroxybutyrate synthesized by ketogenesis in the liver are released to the blood stream where acetone, the third ketone body is produced.

• 5. acetoacetate is somewhat unstable and can sponteously or enzymaticallylose its carboxyl group to form acetone. Thus, the ketone body acetone is not actually a product of the metabolic pathway ketogenesis.

• 6. the ketone body acetone present in the blood stream is a volatile substance that is mainly excreted by exhalation. Its sweet odor is detectible in the breath of a diabetic.

• 7. the amount of acetone present is usually small compared to the concentrations of the other two ketone bodies.

• Steps in the process of Ketogenesis:

step 1: first condensation:

Ketogenesis begins as two acetyl CoA molecules combine to produce acetoacetate CoA, a reversal af the step of the B- oxidation.

Step 2: second condensation:

Acetoacetyl CoA then reacts with a third acetyl CoA and water to produced 3-hydroxy-3-methlglutary CoA and CoA-SH

• Step 3: Chain cleavage. HMG-CoA is then cleaved to acetyl CoA and

Acetoacetate.

• Step 4: Reduction: Acetoacetate is reduced to B-hydroxybutyrate. The

reducing agent is NADH.

KETOSIS

• The over all accumulation of ketone bodies in the blood and urine. And it is often detectable by the smell of acetone on a person’s breath; acetone is very volatile and is excreted through the lungs.

• KETONEMIA

Excess accumulation of ketone bodies in blood ( 20 mg/ 100 mg) .

• KETONURIA

At level of 70 mg/ 100 mL, the renal threshold is exceeded, and ketone bodies are extracted in the urine.

• The symptoms of the mild ketosis that occurs as the result of such dieting include headache, dry mouth, and sometimes foul- smelling breath.

• Two of the three ketone bodies, acetoacetate, B-hydroxybutyrate are acids. Their presence in blood causes a slight but significant decrease in blood pH. This can result in acidosis.

• In severe ketosis, the symptoms include heavy breathing and increased urine output that can lead to dehydration. Ultimately, the condition can cause coma and death.