Fatty acid oxidation- (General introduction)-Lecture-1   

A fatty acid contains a long hydrocarbon chain and a terminal carboxylate group. The hydrocarbon chain may be saturated (with no double bond) or maybe unsaturated (containing double bond)-figure-1.

Figure-1- showing saturated and unsaturated fatty acids.

Sources of fatty acids

Fatty acids can be obtained from-

• Diet
• Adipolysis
• De novo synthesis

Functions of fatty acids

Fatty acids have four major physiological roles.

1) Fatty acids are building blocks of phospholipids and glycolipids.

2) Many proteins are modified by the covalent attachment of fatty acids, which target them to membrane locations

3) Fatty acids are fuel molecules. They are stored as triacylglycerols. Fatty acids mobilized from triacylglycerols are oxidized to meet the energy needs of a cell or organism.

4) Fatty acid derivatives serve as hormones and intracellular messengers e.g. steroids, sex hormones, and prostaglandins.

Triglycerides

• Triglycerides are highly concentrated stores of energy because they are reduced and anhydrous.
• The yield from the complete oxidation of fatty acids is about 9 kcal g-1 (38 kJ g-1)

Triacylglycerols are nonpolar and are stored in a nearly anhydrous form, whereas much more polar proteins and carbohydrates are more highly hydrated.

Triglycerides V/S Glycogen

• A gram of nearly anhydrous fat stores more than six times as much energy as a gram of hydrated glycogen, which is likely the reason that triacylglycerols rather than glycogen were selected in evolution as the major energy reservoir.
• The glycogen and glucose stores provide enough energy to sustain biological function for about 24 hours, whereas the Triacylglycerol stores allow survival for several weeks.

Provision of dietary fatty acids

Most lipids are ingested in the form of triacylglycerols, that must be degraded to fatty acids for absorption across the intestinal epithelium. Free fatty acids and monoacylglycerols obtained by the digestion of dietary triglycerides are absorbed by intestinal epithelial cells. Triacylglycerols are resynthesized and packaged with other lipids and apoprotein B-48 to form chylomicrons, which are then released into the lymph system.

Figure-2- Showing digestion and transportation of triglycerides.

Provision of fatty acids from adipose tissue

The triacylglycerols are degraded to fatty acids and glycerol by hormone-sensitive lipase. The released fatty acids are transported to the energy-requiring tissues (figure-3). The enzyme hormone-sensitive lipase also known as, triacylglycerol lipase, is activated by glucagon and catecholamines through the cAMP-mediated cascade. This enzyme is inhibited by methylxanthines such as caffeine and theophylline. Insulin antagonizes the effect of lipolytic hormones.

Figure-3- Provision of fatty acids through Adipolysis.

Transportation of free fatty acids

• Free fatty acids—also called unesterified (UFA) or non-esterified (NEFA) fatty acids—are fatty acids that are in the unesterified state.
•  In plasma, longer-chain FFA are combined with albumin, and in the cell, they are attached to a fatty acid-binding protein.
•  Shorter-chain fatty acids are more water-soluble and exist as the un-ionized acid or as a fatty acid anion.
•  By these means, free fatty acids are made accessible as a fuel in other tissues.

Types of fatty acid oxidation

Fatty acids can be oxidized by-

1) Beta oxidation- Major mechanism, occurs in the mitochondria matrix. 2-Carbon units are released as acetyl CoA per cycle.

2) Alpha oxidation- Predominantly takes place in the brain and liver, one carbon is lost in the form of CO2 per cycle.

3) Omega oxidation- Minor mechanism, but becomes important in conditions of impaired beta-oxidation

4) Peroxisomal oxidation- Mainly for the trimming of very-long-chain fatty acids.

To be continued in the next lecture…