Ketosis

 Ketosis

Ketone Bodies

Formation (Ketogenesis)-Acetyl CoA is produced during Glycolysis cycle and β-oxidation of fats which combines with oxaloacetic acid to enter in Krebs’ cycle. If glucose supply is low then this acetyl CoA condenses to form aceto-acetyl CoA in the liver which produces aceto-acetic acid. The acetoacetic acid is then reduced to β-hydroxybutyric acid which after decarboxylation forms acetones. Acetic acid, acetone and β-hydroxybutyric acid are called ketone bodies.

The process of formation of ketone bodies is called ketogenesis.

Conditions leading to ketosis

The following conditions produce ketosis:

(a) Diabetes mellitus

(b) Starvation

(e) High fat or low carbohydrate diet

(f) Muscular exercise

Source of ketone bodies (Ketogenic substances)

The ketogenic substances arise from the following-

(1) All fatty acids- Approximately 90% of food fat. Glycerol part oxidizes as carbohydrates. Hence, this part is anti ketogenic.

(2) Proteins- ketogenic amino acids- 40%of all are ketogenic, rest are anti ketogenic.

Site of formation of ketone bodies

Liver is the only site where ketone bodies are normally formed since concentration of ketone bodies have been found to be higher in the hepatic vein than in other veins

Anti ketogenic substances

These are substances which prevent the formation of ketone bodies. They include the following:

(1) All carbohydrates,

(2) 60% of proteins (antiketogenic amino acids) from which sugar may be formed

(3) 10% of fats (the glycerol part).

Utilization of ketones

Ketone bodies are utilized rapidly and independently in many tissues with the production of CO₂ and H₂O. A significant amount of the normal energy requirement of the body is derived from this source. Human brain and other tissues can utilize appreciable amount of ketone bodies during prolonged starvation. Ketones can be utilized freely, without any sugar being oxidized.

 

Ketosis

Accumulation of abnormal amount of ketone bodies in the tissue as also in tissue fluids is called ketosis where the urinary excretion of β-hydroxybutyric acid exceeds 200 mg daily (normal, 5-10 mg).

Role of Endocrines on Ketosis

1. Anterior pituitary- growth hormone or somatotrophic hormone produces ketosis in diabetes mellitus due to inhibition of insulin secretion and depression of Glycogenesis.

2. Pancreas-Insulin prevents ketosis. It increases liver glycogen, prevents mobilization of fats from the depots thus reduces liver fats. Consequently fat oxidation is reduced and more carbohydrates oxidize. This leads to less ketone formation, thus Insulin is antagonistic to the growth or somatotrophic hormone of anterior pituitary.

3. Adrenal cortex- Glucocorticoids of adrenal glands are adipogenetic. It means they mobilize depot fat to the liver for oxidation.

4. Thyroid- Thyroxin increases ketosis due to decrease in liver glycogen and its consequent loading with fat.

Phospholipids (Synonym-Phosphatides)

Chemistry and classification

Phospholipids belong to the group of conjugated fats, containing sugar alcohol or complex amino alcohol, fatty acid, phosphoric acid and nitrogenous base. They may be classified as follows-

1. Monoamino-monophospholipids- In these compounds there are 1 molecule of phosphoric acid, 2 molecules of fatty acids, I molecule of glycerol and I molecule of nitrogenous base (choline or ethanolamine).The examples are lecithin and Kephalin or cephalin.

2. Diamino-monophospholipids- In these compounds there are I molecule of phosphoric acid and 2 molecules of nitrogenous bases, viz. sphingosine and choline; for example, sphingomyelin.

Distribution

It is described as below-

1. The phospholipids are widely distributed in the body. They remain in the cell membrane as well as in the protoplasm as part of their structure and composition. They are part of element constant of the cells.

2. Brain and nervous tissues contain the maximum amount of all the three varieties, i.e., lecithin, cephalin and sphingomyelin. Sphingomyelin is present chiefly in the nervous tissue and negligible amount in other tissues. But lecithin and cephalin are found in considerable amounts in nervous system.

3. The phospholipids content of a particular organ or tissue is constant both in composition and in amount.

4. The fatty acids in the Phospholipid molecule are more unsaturated than those in the neutral fat. The degree of unsaturation is characteristic of a particular tissue.

5. Phospholipids always remain along with cholesterol. The rise orfall of one is always accompanied by a similar change in the other.

Synthesis

The human body can synthesize phospholipids under suitable conditions provided all other constituents are available as follows-

1. Liver can easily synthesize phospholipids. Phospholipids are daily synthesized by the liver from the intermediate products of fat oxidation.

2. The lipotropic action (reduction of fat content) of choline on liver is due to the fact that choline helps in converting neutral fat into phospholipids (choline). The fat becomes highly diffusible, easily passes out of liver and thus the liver fat is reduced.

3. Phospholipids are also synthesized inside the intestinal epithelium during the absorption of fat.

4. The fact that all tissues contain a constant amount of phospholipids, having  a characteristic composition which indicates that the cells of the different times can, at least to some extent, synthesize their own phospholipids locally.

Synthesis of a typical Phospholipid like lecithin (phosphatidylcholine) is as follows-

In the first step phosphate ester of choline (phosphoryl choline) is formed out of choline and ATP. Phosphoryl choline then reacts with cytidine triphosphate (CTP) forming cytidine diphosphate (CDP) choline and inorganic pyrophosphate (PP). In second step a diglyceride combines with the phosphoryl choline part of cytidine diphosphate choline to form lecithin (phosphatidyl choline) and cytidine monophosphate (GMP), the latter is rephosphorylated by ATP and thus reconverted to CTP.

Diglycerides are formed from the glycerol in the liver, intestine and adipose tissue. The glycerol may be absorbed in the intestine as such or formed in the body from fructose-1-6-diphosphate. The first step in the synthesis of diglycerides from glycerol is the action of enzyme glycerol kinase on ATP and glycerol with the formation of L-a-glycero phosphate. The L-a-glycerophosphate is also formed from fructose-1-6 diphosphate. The 1-a-glycerophosphate reacts with acyl CoA in presence of an enzyme to form the phosphatidic acid. The phosphatidic acid is then hydrolyzed by phosphatase with the formation of p-1-2-diglyceride.

Cephalin

Reaction for the synthesis of cephalin is mostly analogous to those for the synthesis of lecithin. The serine may be formed from glycine or may come from the dietary source.

Sphingomyelin

The sphingomyelin contains fatty acids, phosphoric acid, choline and a complex amino alcohol sphingol or sphingosine. The synthesis of sphingosine has been studied in brain tissue. The first step in the synthesis of sphingosine is the reduction of palmityl CoA to the palmityl aldehyde. The palmityl aldehyde on condensation with serine in presence of pyridoxal phosphate gives rise to dihydrosphingosine. Sphingosine is formed after oxidation of dihydrosphingosine. In vivo the sphingomyelin is synthesized from sphingosine phosphoryl choline.