Cholesterol is one of the essential lipids that are present in cell membranes. It may also be called a harbinger of bile acids and steroid hormones. Any disturbance of the homeostasis in cellular cholesterol causes cardiovascular disease and is linked with atherosclerosis. Cholesterol metabolism in humans is a complex one.
Biological Importance Of Cholesterol
Though cholesterol is believed to be terrible in general, it is not that bad as it has a biological significance and a physiological role. Some of them are:
- It is the crucial component of the cell membrane in humans and animals. It moderates the properties of a membrane, which affects the functioning of membrane protein.
- It is an essential lipid for fat digestion as it is a predecessor of the bile acids.
- Steroids like androgens, estrogens, glucocorticoids, mineralocorticoids are all successors of cholesterol.
- It plays an integral role in the pathogenesis of atherosclerosis.
Metabolism Of Cholesterol And Its Functions
The metabolism of cholesterol is a chain of biochemical reactions, which occurs as the synthesis of cholesterol happens, and it is broken down into simpler forms.
The natural metabolism of cholesterol maintains the balance of cholesterol levels in the body. It assures normal working and existence of the organism.
Tracing how cholesterol synthesizes is a long process. It starts with acetyl-CoA, which synthesizes hydroxymethylglutaryl-CoA or HMG-CoA. The result obtained in this stage is similar to ketogenesis.
When ketogenesis occurs in mitochondria, HMG-CoA, responsible for sterol synthesis, is formed in the cytosol. With the export of acetyl-CoA, the synthesis of fatty acid is dependent on it.
How Is Cholesterol Metabolized?
Anabolism of Cholesterol
From endogenous biosynthesis, cholesterol emerges in the human body. It is synthesized in the endoplasmic reticulum or the liver. The process starts with metabolites of glucose, fatty acids, and amino acids called acetyl-CoA.
The method of synthesis is a multifaceted one. At first, the acetyl-CoA molecules are catalyzed into one acetoacetyl-CoA from two. Later Acetyl-CoA and acetoacetyl-CoA combine to form HMG-CoA. Further, the HMG-CoA catalyzes to generate mevalonic acid or MVA. This process of breakdown is irreversible.
MVA is compressed to make squalene once phosphorylation, dehydroxylation, and decarboxylation happen. After catalysis in the endoplasmic reticulum, squalene generates lanosterol. In the end, this lanosterol is converted into cholesterol, enduring many redox reactions.
Catabolism of Cholesterol
It is again the liver where the catabolism of cholesterol takes place. You will not find cholesterol oxidizing or breaking down into CO2 or H2O. It gets transformed into combinations of cyclopentane poly-hydro phenanthrene through reduction and oxidation.
They try to get into the process of metabolism but are often not allowed to. Cholesterol has many essential physiological functions. It can be converted to adrenal cortical hormones and sex hormones like androgen, estrogen, and progesterone.
The oxidation of cholesterol in the skin to seven de hydrogenated cholesterol is further converted to vitamin D3 through ultraviolet radiation. Bile acid is the oxidized form of cholesterol in the liver.
Transportation Of Cholesterol
The carrying of cholesterol happens both ways: from the liver to the tissue and from tissue to the liver for catabolism. Cholesterol is carried through the blood as a lipoprotein.
Cholesterol, combined with apolipoprotein, forms chylomicron, very low-density lipoprotein or VLDL, low-density lipoprotein or LDL, and high-density lipoprotein or HDL.
Regulation of Cholesterol Metabolism
The maintenance of cholesterol metabolism is a negative feedback regulation that includes transcription level and protein level. Transcription level is the level that regulates genes. The protein level is the degeneration of cholesterol by HMG-CoA.
When the level of intracellular cholesterol is high, the SSD or sterol sensing structure domain of SCAP receives endoplasmic reticulum cholesterol levels and mixes with Insig, which results in different complexities.
Lanosterol or the intermediate cholesterol, on the contrary, promotes degeneration of HMGCR, reducing the cholesterol synthesis.
Cholesterol is both an essential and bad part of the body. It has various fundamental purposes that help in the metabolism of your body.