Lipid metabolism involves a series of different pathways and steps that lead to the degradation and synthesis of lipids in cells, fats could be broken down for energy production or synthesized for structural or functional purposes. The following are the major pathways by which this occurs:
- DIGESTION AND RE-ESTERIFICATION: Digestion is the first step that occurs in lipid metabolism, it is the process by which triglycerides are broken down into smaller monoglyceride units with the help of lipase enzymes. This occurs in the small intestine aided by chemicals from the pancreas (pancreatic lipase family and bile salt-dependent lipase). The second step in lipid metabolism is the absorption of fats, here the fatty acids and monoglycerides obtained from the broken down triglycerides can pass through the intestinal barrier to be resterified back into triglycerides. This occurs in the cytosol of epithelial cells.
- LIPOLYSIS: This is the process by which lipids are broken down, to get energy from lipids, triglycerides must first be hydrolyzed into fatty acids and glycerol. Lipolysis is a cytoplasmic process that occurs when lipids are broken down. The Krebs cycle uses acetyl CoA, which is produced via the beta-oxidation of fatty acids. The glycerol generated from triglycerides enters the glycolysis pathway as dihydroxyacetone phosphate(DHAP) after lipolysis. In the cytosol of the cell (for example a muscle cell), the glycerol will be converted to glyceraldehyde 3-phosphate or DHAP, which is an intermediate in the glycolysis, to get further oxidized and produce energy. However, the main steps of fatty acid catabolism occur in the mitochondria. LIPOLYSIS as a whole is induced by either glucagon or epinephrine
- LIPOGENESIS: This is the process by which fatty acids, triglycerides, cholesterol, steroids, and bile salts are synthesized from excess acetyl CoA created during glycolysis. It begins with acetyl CoA and proceeds with the addition of two carbon atoms from another acetyl CoA; this process is repeated until the fatty acids are of
the desired length. Because this is a bond-creating anabolic activity, ATP is used. Triglycerides and lipids, on the other hand, are a good way to store the energy that carbs provide. Triglycerides and lipids are high-energy molecules that are stored in adipose tissue until they are needed. Basically, the lipids are synthesized from non-lipid precursors. It is a pathway for the metabolism of excess carbohydrates and is activated by high carbohydrate availability.
4. KETOGENESIS: Ketone bodies are created by the diversion of excess acetyl CoA generated by fatty acid oxidation and the Krebs cycle. If the body’s glucose levels are too low, these ketone bodies can be used as a fuel source and they also default energy sources for some specific tissues. When ketones are produced faster than they can be used, they can be broken down into CO2 and acetone. Exhalation is used to get rid of the acetone. Basically, it is the biochemical process through which organisms produce ketone bodies by breaking down fatty acids and ketogenic amino acids.
5. FATTY ACID OXIDATION: The aerobic degradation of fatty acid into acetyl-CoA units is known as fatty acid oxidation. NAD and FAD are used by fatty acids to move through this pathway as CoA derivatives. They are activated with ATP in the presence of CoA-SH and acyl-CoA synthetase before oxidation. In the human body, fatty acid oxidation occurs in many regions of the cell: the mitochondria, where only beta-oxidation occurs; the peroxisome, where alpha- and beta-oxidation occurs; and the endoplasmic reticulum, where omega-oxidation occurs. Long-chain fatty acids need to be converted to fatty acyl-CoA in order to pass across the mitochondria membrane. The main products of the beta-oxidation pathway are acetyl-CoA (which is used in the citric acid cycle to produce energy), NADH, and FADH.
6. CHOLESTEROL BIOSYNTHESIS: Cholesterol is formed in the endoplasmic reticulum of the liver cells, and it starts with acetyl-CoA, which is produced in large quantities after an oxidation event in the mitochondria. The mevalonate pathway is a set of enzyme reactions that results in cholesterol production. In this series of reactions, the conversion of hydroxyl-methyl glutaryl-coenzyme A (HMG-CoA) to mevalonate is the rate-limiting step. The cholesterol produced can then go on to form vitamin D, steroid hormones, and bile salts.
Acetic acid is a central precursor of fatty acids
Acetic acid is essential for fat and glucose metabolism in the body. It works as a signaling molecule in bovine hepatocytes, activating the AMPK signaling system and increasing lipolysis while decreasing lipid synthesis. Acetyl-CoA produced in mitochondria from carbohydrate or amino acid catabolism needs to reach the cytosol to initiate de novo synthesis of fatty acids. All eukaryotes analyzed so far use a citrate/malate shuttle to transfer acetyl group equivalents from the mitochondrial matrix to the cytosol. Most of the acetyl-CoA which is converted into fatty acids is derived from carbohydrates via the glycolytic pathway.
Synthesis and breakdown of Cholesterol
The synthesis of cholesterol takes place in the cytoplasm and endoplasmic reticulum of every nucleated cell, most especially hepatic cells. The breaking down of cholesterol only takes place in the liver.
HMG-CoA synthase starts the cholesterol synthesis process by converting acetyl-CoA and acetoacetyl CoA to 3-hydroxy-3-methylglutaryl CoA (HMG-CoA). When the liver excretes cholesterol into biliary secretions, cholesterol is broken down.
Cholesterol synthesis is controlled by the conversion of hydroxyl-methyl glutaryl-coenzyme A (HMG-CoA) to mevalonate, which requires a series of enzymatic processes known as the mevalonate pathway. The liver converts cholesterol to bile acids, which can subsequently be conjugated with glycine, taurine, glucuronic acid, or sulfate and expelled as bile acid.