Lipid Metabolism: Cholesterol, Hormones & Transport

• Lipids Part 2 covers Isoprenoid Structures.
• An objective is for the 3 categories of terpenes, with their naming conventions and examples, to be described.
• The process of cholesterol synthesis should be outlined.
• The basic structure and function regarding sterols should be identified.

Isoprenoids

• Isoprenoids include terpenes, mixed terpenes, and steroids.

Terpenes

• Isoprenoid units are linked together, and are sometimes in alcohol, aldehyde, or ring form.
• Smallest terpene = 2 isoprene units linked together and is a monoterpene.
• Diterpene = 4 isoprenes.
• Triterpene = 6 isoprenes.
• Farnescene = a sesqui terpene.
• Squalene = a triterpene.
• Beta carotene = a tetraterpene.
• Beta-Carotene is used to produce Vit A
• Use.

Mixed Terpenes

• A mixed terpene contains terpenes with a non-terpene component attached.
• CoQ is important in ETC.
• Vit K is active in clotting and formed in the liver.
• Farnesylated proteins support cell signalling

Steroids

• Steroids stem from 6 isoprene units.
• They are made from cholesterol contain four fused rings plus various substituents.
• Along with phospholipids (PLs) it helps to make up most of the cell mass..

Cholesterol

• The liver uses it to make bile for digesting fats (emulsification in the GI tract) and lipoproteins to carry cholesterol to the tissues.
• LDL receptors recognize and bind to LDL to internalize it allowing a cell utilizes the lipids and cholesterol.
• LDL is broken down and cholesterol is released and used to make membranes.
• LDL molecules are relatively small and can pass through a cell membrane.

Familial Hypercholesteremia

• A rare, inherited defect in LDL-receptors often relates to liver/blood LDL-reception due to an inborn error of metabolism.
• Familial Hypercholesteremia leads to high LDL and Cholesterol in liver, so can increases risk of myocardial infarction.

Cholesterol Synthesis

• The four main steps are in the endoplasmic reticulum (ER):
  • Condensation of 3 acetyl CoA into mevalonate
  • Creation of isoprene units, in forms of isopentenyl pyrophosphates
  • Creation of squalene (a triterpene requires 6 isopentenyl pyrophosphates)
  • Cyclization of squalene into cholesterol

HMG-CoA Reductase

• The enzyme "HMG-CoA Reductase" is utilized to form an initial HMG-CoA through to initiate Ketogenesis, with 3 Acetyl required. Reductase is necessary to synthesize HMG-CoA during this stage.
• Statins act as an enzyme, having the property of reducing blord bloud LDL.
• The enzyme utilization in the body is under heavy genetic influence. As such it needs to be heavily controlled over either promotion of of inhibitio.
  • Inhibited by high intracellular levels of cholesterol, which blocks transcription of HMG-CoA reductase gene.
  • Activates if needs be though translation of HMG-CoA to reach a more desired count. This is only implemented should an initial value/count not be acceptable.

Covalent influences

• Elements or functions and cause an the creation of cholesterol/sterol-related properties.
• If is is heavily influenced with various de-phosphorylized elements a synthesis will take will occur to ensure the production of cholesterol.
• This process is assisted ( or influenced, depending on its need) with Insulin, as it can increase the rate or product rate when available for use.
• Glucagon may assist in lowering production, should energy become scarce or low, within the body. In this case, glucose becomes the primary fuel source, at which point triglyceride or steroid production decreases.

Clinical Connection

• Normally, Insulin is released when blood-sugar levels are high, helping move sugar into cells.
• If blood sugar is high over an extended time, cells may stop responding to insulin, causing insulin resistance and elevated insulin blood levels and hyperinsulinemia occurs.

Type 2

• In Type 2 diabetes, resistance to insulin hormone and high blood sugar occur,
• An individual's reaction depends on the body's resistance in insulin absorption
• If blood is sugar high is persistent, with a strong resistance to insulin absorption, increases the risk of cardiovascular disease (and possibly diabetes) due to high LDL levels.
• This potentiality can be reduced though Hormone maintenance, and lowering the bodies hormone resistance.

Isoprenoids

• The main source for steroids starts with in cholesterol itself. The bodies production occurs utilizing specific enzymes to do so, forming most natural sterol-based reactions.

Plant sterols and its derivatives

• Plant sterols have a similar structure to cholesterol and their own membrane-specific properties.
• Plant-derived sterols hinder cholesterol production, while also helping reduce lipid-storage and related disease and lowers LDL levels.
• Cardiac glycosides are derivatives of plant sterols that contain a ringed molecule.
• Glycoside, Digoxin is a cardiac specific with that structure.

Explore lipid metabolism, covering steroid hormone synthesis via the mevalonate pathway and the roles of LDL and HDL in cholesterol transport. Understand how cholesterol synthesis is regulated, the impact of dietary carbohydrates, and hormonal influences. Learn about triacylglycerols and sphingomyelin synthesis.