Fatty acids are long chains of unsubstituted carbon-carbon bonds (tail) ending in a carboxylic acid (head). The carbon chain portion, composed solely of carbon and hydrogen, is nonpolar and hydrophobic, while the carboxylic acid group is hydrophilic, together establishing fatty acids as amphipathic molecules. Hydrocarbon tails with the maximum number of bonds to hydrogen with all single C—C bonds are described as saturated. Fatty acids with at least one double C=C bond in their hydrocarbon tails are described as unsaturated. Higher degrees of saturation offer a more reduced molecule that can be oxidized further for energy release (saturated fatty acids store more energy). Fatty acids can be used as building blocks to compose other lipid molecules, generally characterized as hydrophobic organic compounds with low water-solubility.
Fatty acids are usually metabolized by the addition or removal of 2-carbon portions (acetyl groups), thus maintaining tails with an even number of carbons.
Due to their hydrophobic nature, fats require special transport through aqueous environments such as in blood via lipoproteins, which are water-soluble phospholipid shells with associated apoproteins surrounding a hydrophobic lipid core.
Beginning in digestion, triglycerides (compounds of 3 fatty acid tails on a 3-carbon glycerol backbone) are digested by the pancreatic enzyme lipase into 2 (free) fatty acids and 1 monoglyceride. Then, being hydrophobic and relatively small, these molecules are able to diffuse across the cellular membrane of epithelial cells in the small intestines (absorption). Once in the cytosol, free fatty acids and monoglycerides are reconstructed back into triglycerides, which are gathered into a lipoprotein assembly of fat and protein called a chylomicron that leaves the cell via exocytosis and is delivered to blood circulation via lymphatic ducts. Liver and adipose cells interact with chylomicrons to breakdown the triglycerides once more so that free fatty acids and monoglycerides can once again diffuse into these cells (where the triglycerides are once again reconstructed for storage).
In addition to chylomicrons, fats can be mobilized and transported via the blood protein albumin or other lipoproteins such as VLDL (very low density lipoproteins), LDL (low density lipoproteins), and HDL (high density lipoproteins). Stored triglycerides are broken down in cells by the enzyme lipase for transport as free fatty acids.
The process of beta-oxidation occurs in mitochondria to break down fatty acids into 2-carbon acetyl-CoA molecules which can then enter the citric acid cycle. Each cleavage, which takes place at the second (beta) carbon from the end of the hydrocarbon chain, produces 1 FADH2 and 1 NADH to go on to the electron transport chain. Finally, the 3-carbon glycerol backbone is converted to a glycolysis intermediate or used for gluconeogenesis. The liver can also convert acetyl-CoA to water-soluble ketone bodies that can travel through the blood to be converted back to acetyl-CoA for the citric acid cycle in other cells.
Saturated fats are characterized as being fully reduced with the maximum number of bonds to hydrogen and single C—C bonds along its fatty acid tail. These molecules have greater reducing potential than unsaturated fats, providing greater energy storage.
Unsaturated fats contain one or more double C=C bonds in their fatty acid tails, a less than fully reduced (partially oxidized) form compared to saturated fats. Most of the double bonds are found in the Z/cis conformation.
Ketogenesis occurs in the liver in conditions of high acetyl-CoA and low insulin levels, converting acetyl-CoA to ketone bodies, small polar molecules that can be transported in the blood to cells, including in the brain, to supply energy from their conversion back to acetyl-CoA and the citric acid cycle.
Fatty acid synthesis proceeds using acetyl-CoA for a 2-carbon elongation of the hydrocarbon chain. Fatty acids are in turn used for synthesis of more complex lipids such as phospholipids for cell membranes. Steroids are lipids which are formed from precursors to other biologically active molecules (e.g. cholesterol, cortisol, testosterone).
Whereas nucleic acid and amino acid polymers are constructed based on templates (DNA for DNA replication and RNA transcription; mRNA for polypeptides), lipids and polysaccharides are synthesized through series of chemical reactions with requisite substrate and enzyme concentrations but without a template.
Amino acids for the synthesis of proteins come from the diet (essential amino acids which cannot be synthesized), from amino acid synthesis (non-essential amino acids), or from the breakdown of existing proteins.
In digestion, proteins are digested into amino acids (mono-, di-, and tri-forms) in the small intestine by trypsin, chymotrypsin, and carboxypeptidase, and absorbed across epithelial cells into circulation.
Amino acids can be degraded by deamination to remove the nitrogen group (converted to urea), leaving a carbon chain that can be converted for use in metabolic processes such as the citric acid cycle, gluconeogenesis, and ketogenesis.
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