Fats can be synthesized from both carbohydrates and proteins.
The evidence is given below:
1. From Carbohydrates:
It is an experimental fact that animals can deposit fat practically on fat-free diet (Fig. 10.30.) Young pigs fed on barley deposit more fat than can be accounted for from the protein and fat content of barley. So the carbohydrates must have been used for the purpose. It has been found that palmitic and stearic acids are rapidly synthesized but the synthesis of unsaturated acids is very slow.
The body is able to introduce one or two double bonds but not more. So that the highly unsaturated fatty acids like linoleic acid or linolenic acid or arachidonic acid which are known as essential fatty acids cannot be synthesized.
I. Synthesis of Saturated Fatty Acids:
It is now an established fact that fatty acids are synthesized from acetate which is activated by reaction with CoASH and ATP in presence of acetyl CoA synthetase to form active acetyl CoA. This is carboxylated to form malonyl CoA in presence of CO2 + Mn++ and acetyl CoA carboxylase (dependent upon enzyme-bound biotin).
Then acetyl and malonyl groups are transferred to the acyl carrier protein (ACPSH) with the help of enzyme fatty acyl transacylase and the CoASH becomes free. Acetyl ACP and malonyl ACP thus formed condense by a sulphydryl enzyme to form acetoacetyl ACP with the liberation of CO2 and one molecule of ACPSH.
Acetoacetyl ACP is reduced by dehydrogenase in presence of NADPH + H+ (formed during glucose oxidation in hexose monophosphate shunt, HMS) to β-hydroxybutyryl ACP which is further unsaturated at α, β-position by enzyme enoyl hydrase then α-, β-unsaturated butyryl ACP is reduced by dehydrogenase in presence of NADPH + H+ to butyryl ACP.
The 2C acetate is thus elongated to 4C chain, i.e., butyryl ACP which may further be elongated by 2C in each above cycle of reactions adding malonyl ACP in each cycle of above reaction. Finally, the fatty acid is formed by deacylase when fatty acid ACP is cleaved to form (say in case of 16C fatty acyl ACP i.e., palmityl ACP) palmitic acid and ACPSH. The synthesis of saturated fatty acids may be presented schematically (Fig. 10.31).
It is indicated that acetic acid derived from glucose, fatty acids and amino acids go to form fatty acids in the body. The mitochondrial and microsomal systems are concerned with the synthesis of fatty acids. The detail mechanism is not known in either case but it is proved that in the former system elongation of fatty acid carbon chain and unsaturated fatty acid formation takes place which is sensitive to avidin and not biotin dependent one and in the latter system carboxylation of acetyl CoA, conversion of malonyl CoA to fatty acid and phospholipid formation takes place.
Several members of the vitamin B complex are involved in the process. Thiamine is necessary for the conversion of sugar into fats. Riboflavin, pyridoxine and nicotinic acid play a similar but subsidiary role.
II. Synthesis of Unsaturated Fatty Acids:
Schoenheimer and his associates have reported that unsaturated fatty acids are synthesised from saturated fatty acids. A microsomal system is involved for such synthesis. The liver contains such system for the synthesis of oleic and palmitoleic acids from stearyl CoA and palmitoleoyl CoA respectively. NAD or NADP is required for carrying out the process.
2. From Proteins:
Since nearly 60% of proteins can be converted into carbohydrate, it is reasonable to expect that some of this sugar may be available for conversion into fats. Recent study with isotopes has definitely shown that such conversion is possible. Certain members of vitamin B family are also important in this respect. Animals kept on pure protein diet with a liberal supply of several members of vitamin B group can deposit fats and that this synthetic fat is similar in composition to that which is synthesised from carbohydrate food.
Factors Influencing Lipogenesis:
Lipogenesis (fatty acid synthesis) is depressed in diabetes and starvation. It is possibly due to decreased production of acetyl CoA or of NADP or NAD due to defective carbohydrate metabolism. It is postulated that in diabetic and starved rats, the activity of acetyl carboxylase is decreased. Citrate and other components of Krebs cycle have got some stimulating effects in fatty acid synthesis. Besides this, the citrate also helps lipogenesis by donation acetyl CoA units. Rate-limiting factor in fatty acid synthesis is the carboxylation of acetyl CoA.
Synthesis of Glycerol:
Glycerol is synthesised from glucose. Glucose is first converted into two molecules of triosephosphate, i.e., dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, the latter is convertible to former which gives rise to glycerol.
Essential Fatty Acids:
The fats which are synthesised in the body (endogenous fat) from the fatty acid derived from non-lipid sources, i.e., carbohydrates and proteins, cannot serve all the functions of exogenous fat, e.g., maintenance of proper growth and nutrition. So it is indicated that synthesis of fat in the body is restricted to a limit where some unsaturated fatty acids are not synthesised.
Since some fatty acids cannot be synthesised and, on the other hand, required by the body so they should be supplied from outside through diet and are called essential fatty acids like the essential amino acids required for growth and nutrition.
Highly unsaturated fatty acids, such as, linoleic acid or linolenic acid or arachidonic acid, are essential for proper growth and nutrition and may be called essential fatty acids. It has however been observed that linoleic acid might be converted into arachidonic acid and so the latter can be spared if linoleate is adequately supplied in diet. Pyridoxine (vitamin B6) helps in the process of conversion.
Functions of Essential Fatty Acids:
i. They help in normal growth
ii. They are structural components of cells.
iii. They are in some way concerned with normal reproductive capacity.
iv. They are responsible for the maintenance of normal healthy skin.