Biochemistry of Lipid Metabolism

The process of breaking down large fat molecules into smaller ones that can be absorbed by the body. This occurs in the small intestine with the help of bile and lipases.

Tiny, water-soluble spheres formed from bile salts, fatty acids, monoglycerides, cholesterol, and fat-soluble vitamins. They help transport digested lipids across the intestinal wall.

The process of taking digested fats from the small intestine into the cells lining the intestine.

The process of re-building triglycerides from absorbed fatty acids and monoglycerides inside the intestinal cells.

A large lipoprotein responsible for transporting absorbed dietary fats from the intestines to other tissues of the body.

A specialized system involved in the transport of chylomicrons due to their large size. It carries chylomicrons to the circulatory system.

Specific proteins that help in the formation and packaging of chylomicrons by attaching to them.

The primary apolipoprotein found in chylomicrons, involved in their assembly and transport.

A lipoprotein involved in reverse cholesterol transport, picking up excess cholesterol from peripheral tissues and returning it to the liver.

The process of synthesizing triglycerides and fatty acids, primarily occurring in the liver and adipose tissue during the fed state.

A key step in lipogenesis involving the production of malonyl-CoA, a precursor for fatty acid synthesis.

The process of breaking down triglycerides into glycerol and free fatty acids.

A three-carbon alcohol that is a component of triglycerides.

Hormone that promotes lipogenesis by activating ACC activity, increasing glucose uptake, and ensuring glycerol-3-phosphate availability.

An enzyme activated by insulin that plays a crucial role in lipogenesis.

A precursor for triglyceride assembly, derived from glucose metabolism.

Fatty acids and glycerol are released from triglycerides in chylomicrons by an enzyme called lipoprotein lipase (LPL). LPL is located on the surface of endothelial cells in tissues like muscle and adipose tissue. In the context of lipid metabolism, this process allows tissues to access fatty acids for energy and storage.

The remnants of chylomicrons, now depleted of triglycerides, primarily contain cholesterol and phospholipids. These remnants are taken up by the liver by specific receptors, primarily LDL receptor-related protein (LRP).

Very low-density lipoproteins (VLDL) are synthesized in the liver and contain high amounts of triglycerides and cholesterol. VLDL is secreted into the bloodstream, where it functions to deliver triglycerides to peripheral tissues like muscle and adipose tissue.

When VLDL interacts with lipoprotein lipase (LPL), triglycerides are broken down. This process gradually transforms VLDL into intermediate-density lipoproteins (IDL) and ultimately into low-density lipoproteins (LDL), which are primarily composed of cholesterol and phospholipids.

LDL serves as the main transporter of cholesterol to peripheral tissues, including muscle, adrenal glands, and gonads. LDL receptors on the surface of these target cells mediate endocytosis of LDL particles, allowing them to take up cholesterol for important functions like membrane synthesis, steroid hormone production, and bile acid formation.

LDL receptors on the surface of cells bind to LDL particles, triggering endocytosis. This process brings LDL particles inside the cell, where cholesterol is either stored or utilized based on the cell's needs. Once the receptor releases LDL, it's recycled back to the cell surface for further LDL uptake.

An enzyme activated by glucagon and epinephrine, which helps break down triglycerides into diacylglycerol and then monoacylglycerol.

The process of converting FFAs into Acetyl-CoA, NADH, and FADH2, which are then used to generate ATP.

A key regulator of lipogenesis, activated by insulin, and responsible for converting Acetyl-CoA into Malonyl-CoA, a precursor for fatty acid synthesis.

Atherosclerosis is a disease where plaque builds up inside the arteries. This plaque can restrict blood flow, leading to heart attacks and strokes.

Cats have a lower risk of atherosclerosis compared to humans due to their unique lipid metabolism, which is different from ours.

Cats have a distinct lipid metabolism compared to humans, with lower plasma cholesterol levels and a different lipoprotein profile.

Cats' natural diet, being high in protein and low in carbohydrates, doesn't favor the development of lipid abnormalities associated with human atherosclerosis.

Cats experience fewer pro-inflammatory states, which are essential for atherosclerosis development, contributing to their resistance to the disease.

Cats may have genetic factors that protect against atherosclerosis. Their lipid-handling mechanisms might reduce cholesterol accumulation in the arteries.

The similarities in atherosclerosis manifestation between cats and humans makes them a valuable model for studying the disease.

The findings in Korat cats suggest a potential genetic predisposition to atherosclerosis within the breed.

A multi-step enzymatic pathway starting from Acetyl-CoA that produces cholesterol. It requires significant energy (ATP) and reducing power (NADPH).

The first step in cholesterol synthesis, where two Acetyl-CoA molecules are combined to form mevalonate. This step requires the enzymes thiolase, HMG-CoA synthase, and HMG-CoA reductase.

A series of reactions converting mevalonate into isopentenyl pyrophosphate (IPP), a 5-carbon unit that serves as a building block for larger molecules. This step requires enzymes like mevalonate kinase and phosphomevalonate kinase.

The process of combining multiple IPP units into a 30-carbon molecule called squalene. This involves enzymes like squalene synthase.

The conversion of squalene into a 30-carbon cyclic molecule called lanosterol. This involves the enzymes squalene monooxygenase and oxidosqualene cyclase.

The final step in cholesterol synthesis where lanosterol undergoes 19 additional reactions, including demethylation, reduction, and isomerization, to form cholesterol.

The main regulatory mechanism for cholesterol synthesis, controlling the rate of the reaction. It is regulated by feedback inhibition, hormonal regulation, and sterol regulatory element-binding proteins (SREBPs).

A type of feedback loop that regulates cholesterol synthesis, where high levels of cholesterol in the body inhibit HMG-CoA reductase activity, reducing the rate of cholesterol synthesis.