Fatty acid metabolism

[1] In catabolism, fatty acids are metabolized to produce energy, mainly in the form of adenosine triphosphate (ATP).

In anabolism, intact fatty acids are important precursors to triglycerides, phospholipids, second messengers, hormones and ketone bodies.

In another type of anabolism, fatty acids are modified to form other compounds such as second messengers and local hormones.

Between meals they are released as follows: In the liver oxaloacetate can be wholly or partially diverted into the gluconeogenic pathway during fasting, starvation, a low carbohydrate diet, prolonged strenuous exercise, and in uncontrolled type 1 diabetes mellitus.

[10] In the liver, therefore, oxaloacetate is unavailable for condensation with acetyl-CoA when significant gluconeogenesis has been stimulated by low (or absent) insulin and high glucagon concentrations in the blood.

All cells with mitochondria can take up ketones from the blood and reconvert them into acetyl-CoA, which can then be used as fuel in their citric acid cycles, as no other tissue can divert its oxaloacetate into the gluconeogenic pathway in the way that this can occur in the liver.

[10] The occurrence of high levels of ketones in the blood during starvation, a low carbohydrate diet, prolonged heavy exercise, or uncontrolled type 1 diabetes mellitus is known as ketosis, and, in its extreme form, in out-of-control type 1 diabetes mellitus, as ketoacidosis.

Fatty acids, stored as triglycerides in an organism, are a concentrated source of energy because they contain little oxygen and are anhydrous.

Since the hydrocarbon portion of fatty acids is hydrophobic, these molecules can be stored in a relatively anhydrous (water-free) environment.

This means that fatty acids can hold more than six times the amount of energy per unit of stored mass.

[17] The fat stores of young adult humans average between about 10–20 kg, but vary greatly depending on gender and individual disposition.

[24] One product of fatty acid metabolism are the prostaglandins, compounds having diverse hormone-like effects in animals.

They are synthesized in the walls of blood vessels and serve the physiological function of preventing needless clot formation, as well as regulating the contraction of smooth muscle tissue.

A significant proportion of the fatty acids in the body are obtained from the diet, in the form of triglycerides of either animal or plant origin.

[28] The digestion products consisting of a mixture of tri-, di- and monoglycerides and free fatty acids, which, together with the other fat soluble contents of the diet (e.g. the fat soluble vitamins and cholesterol) and bile salts form mixed micelles, in the watery duodenal contents (see diagrams on the right).

[31] The chylomicrons circulate throughout the body, giving the blood plasma a milky or creamy appearance after a fatty meal.

The fatty acids are absorbed by the adipocytes[citation needed], but the glycerol and chylomicron remnants remain in the blood plasma, ultimately to be removed from the circulation by the liver.

These fatty acids are combined with glycerol to form triglycerides which are packaged into droplets very similar to chylomicrons, but known as very low-density lipoproteins (VLDL).

Adipose tissue cells store the triglycerides in their fat droplets, ultimately to release them again as free fatty acids and glycerol into the blood (as described above), when the plasma concentration of insulin is low, and that of glucagon and/or epinephrine is high.

The cells of the central nervous system will almost certainly have the capability of manufacturing their own fatty acids, as these molecules cannot reach them through the blood–brain barrier.

[34] However, it is unknown how they are reached by the essential fatty acids, which mammals cannot synthesize themselves but are nevertheless important components of cell membranes (and other functions described above).

[35][36] The diagrams presented show how fatty acids are synthesized in microorganisms and list the enzymes found in Escherichia coli.

[35] These reactions are performed by fatty acid synthase II (FASII), which in general contains multiple enzymes that act as one complex.

FASI is less efficient than FASII; however, it allows for the formation of more molecules, including "medium-chain" fatty acids via early chain termination.

[38] Once a 16:0 carbon fatty acid has been formed, it can undergo a number of modifications, resulting in desaturation and/or elongation.

[39][40] Abbreviations: ACP – Acyl carrier protein, CoA – Coenzyme A, NADP – Nicotinamide adenine dinucleotide phosphate.

NADPH is also formed by the pentose phosphate pathway which converts glucose into ribose, which can be used in synthesis of nucleotides and nucleic acids, or it can be catabolized to pyruvate.

[34] In humans, fatty acids are formed from carbohydrates predominantly in the liver and adipose tissue, as well as in the mammary glands during lactation.

[43] High plasma levels of insulin in the blood plasma (e.g. after meals) cause the dephosphorylation and activation of acetyl-CoA carboxylase, thus promoting the formation of malonyl-CoA from acetyl-CoA, and consequently the conversion of carbohydrates into fatty acids, while epinephrine and glucagon (released into the blood during starvation and exercise) cause the phosphorylation of this enzyme, inhibiting lipogenesis in favor of fatty acid oxidation via beta-oxidation.

[34][42] Disorders of fatty acid metabolism can be described in terms of, for example, hypertriglyceridemia (too high level of triglycerides), or other types of hyperlipidemia.