Study Notes on Ketone Bodies

The below mentioned article provides a study note on the ketone bodies. After reading this article you will learn about: 1. Synthesis and Utilization of Ketone Bodies 2. Role of Ketone Bodies as an Aid to Diagnosis 3. Biochemical Changes in Ketosis and 4. Clinical Conditions of Ketosis.

Ketone Bodies:

There are three ketone bodies namely:

(1) Acetoacetic acid

(2) Beta hydroxy butyric acid and

(3) Acetone.

Ketone bodies are also known as ‘acetone bodies’. Formation of ketone bodies is known as ketogenesis. The ketone bodies are synthesized in the liver even under normal conditions.

Synthesis and Utilization of Ketone Bodies:

The ketone bodies are synthesized in the liver by the following reaction mechanism:

These ketone bodies cannot be utilized by the liver because the enzymes needed to activate them are absent or low in activity and hence these ketone bodies are supplied to the peripheral tissues for oxidation.

In the peripheral tissues the ketone bodies are utilized in the following manner:

Only acetoacetic acid and beta hydroxybutyric acid are easily oxidized by the extra hepatic tissue. Oxidation of acetone is difficult; hence it is excreted in urine in large amounts than other ketone bodies, Acetone is also eliminated through the lungs; hence starvation and diabetic patients show an alcoholic smell in their breath.

Role of Ketone Bodies as an Aid to Diagnosis:

There are three ketone bodies viz.:

(1) Acetoacetic acid;

(2) Beta hydroxy butyric acid;

(3) Acetone.

Ketone bodies are also known as Acetone bodies. Formation of ketone bodies is known as ketogenesis. The ketone bodies are synthesized in the liver even under normal conditions. The ketone bodies are produced from Acetyl CoA which comes from three sources.

(1) Glucose

(2) Fatty acids and

(3) Amino acids.

Normal levels of ketone bodies in human beings:

The normal level of ketone bodies in the blood of human beings is less than 1 mg/dl and is excreted in the urine to less than 1 gm./day.

Methods of estimation of Ketone Bodies:

The presence or absence of ketone bodies in the urine is detected by Rothera’s test. Rothera’s test is also carried for the semi-quantitative estimation of ketone bodies in the blood, wherein the results obtained are—

(- ve) — Ketone bodies are less than 1 mg/100 ml of the blood

(+ ve) — Ketone bodies are little more than 1 mg/100 ml of the blood

(+ + ve) — Ketone bodies are about 1.5 mg/100 ml of the blood

(+ + + ve) — Ketone bodies are more than 2 mg/100 ml of the blood

There are two methods for the quantitative estimation of ketone bodies in blood:

(1) Micro diffusion method

(2) Enzymatic method.

The ketone bodies synthesized by the liver will continuously be utilized by the peripheral tissues. The peripheral tissues have a limited capacity to utilize the ketone bodies. If the production of ketone bodies by the liver exceeds the capacity of the peripheral tissues to utilize them, as in diabetics and starvation, then this results in accumulation of ketone bodies in blood; a condition known as ketonemia and consequently there will be an increased excretion of ketone bodies in urine; known as ketonuria. Both ketonemia and ketonuria together are known as ketosis.

Ketosis:

Ketosis or keto acidosis is a condition in which there is an increased accumulation of ketone bodies in the blood (ketonemia) and consequently increased excretion in urine (ketonuria).

Biochemical Changes in Ketosis:

1. Acetoacetic acid and Beta hydroxyl butyric acid are strong acids; their accumulation causes ketoacidosis, thereby lowering the pH of blood.

2. Buffering capacity is disrupted because bicarbonate of the blood decreases.

The low pH caused by ketosis leads to disturbance in the normal buffering mechanism of the blood. This leads to emergence of yet another buffering system in the blood i.e., the muscle proteins are released and hydrolyzed to amino acids which are oxidized releasing ammonia (NH₃). NH₃ takes up H⁺ ions to form NH₄ and thus compensates the acidity of blood. Ammonium ion is more destructive thereby causing more harm to the individual.

3. Along with ketone bodies large amounts of H₂O and Na⁺ ions are lost leading to electrolyte imbalance and dehydration.

Symptoms:

Depression, thirst, fatigue and coma.

Clinical Conditions of Ketosis:

Clinical Conditions in Which Ketosis Occurs:

(1) Starvation:

Includes both post fasting period i.e. 12-24 hours after meal or continuous starvation for days together. During this condition there may be lack of glucose leading to non-entry of glucose into adipose tissue resulting in lowered glycolysis and low intermediates of glycolytic pathway. Low concentration of glyceraldehyde-3-phosphate, an intermediate of glycolysis cannot be converted to glycerol phosphate and therefore there will be no re-esterification of fatty acids resulting in the release of fatty acids from adipose tissue into the blood.

As the period of starvation increases, the glucose concentration in the blood decreases leading to increased release of fatty acids producing more amounts of ketone bodies much more than the peripheral tissues can use them, causing ketosis. The ketone bodies are utilized by all the extra-hepatic tissues except brain in the initial stages. After three weeks of starvation, brain also shifts to the utilization of ketone bodies which leads to the destruction of brain cells due to ketosis.

(2) Diabetes mellitus:

Though glucose is present in large quantities in the blood, it cannot be utilized by the cells, results in the release of fatty acids and overproduction of ketone bodies causing ketoacidosis.

(3) Pregnancy:

During the third trimester of pregnancy, the demand for glucose is doubled and hence there will be overproduction of ketone bodies leading to ketoacidosis.

(4) Lactation:

During lactation more energy is required because glucose is utilized for:

(i) Production of lactose

(ii) Formation of milk fat and

(iii) Synthesis of milk protein casein.

This leads to depletion of glucose to adipose tissue resulting in more release of fatty acids producing more ketone bodies leading to ketosis. Ketosis is generally accompanied with low calcium levels which are referred to as milk fever. This is developed within hours in lactating mothers having twins or more babies which is characterized by sudden fall in blood pH and decrease in milk production.

(5) Febrile diseases:

In fever causing disease there is a demand for glucose for the formation of antibodies thereby depleting glucose to adipose tissue leading to ketosis.

(6) Heavy exercise:

Heavy physical exercise suddenly raises the level of ketone bodies and if the exercise is continued without intake of glucose then it may result in ketosis.

Control:

Starvation ketosis can be controlled by injecting anti-ketogenic substances like glucose and glucose producers like glycerol and glucogenic amino acids like glycine, glutamic acid, alanine, serine etc..