0219 - Lipid Metabolism - RM Flashcards
What is a lipid?
Lipids are the waxy, greasy, and oily constituents of the cell. They are primarily ingested, but can be synthesised according to demand.Lipids can be either fatty acid (long-chain) based, or sterol (ring) based.
What are the three broad roles of lipids in the body?
Biomembrane structure, biosignalling, and energy storage. (this lecture slide will be an exam question)
What is a key quality of fatty acid-based lipids?
Amphiphilicity - The lipid is polar (hydrophilic) at one end, and non-polar (hydrophobic) at the other end (hydrocarbon chain).
Describe a simple lipid. How is it broken down?
A non-polar (hydrophobic) hydrocarbon chain, with a polar (hydrophilic) carboxylic acid group at one end. The chain may have points of unsaturation (double bonds) which are structurally important.They are broken down through ß-oxidation.
Describe a complex lipid. How are they formed and what are their roles?
Complex lipids are two or more fatty acid chains joined to a glycerol backbone. To form a complex lipid, CoA is attached to the Carboxyl group on the simple lipid. This joins with alcohols on the glycerol to generate di and triglicerides.Diglicerides are used for synthesis of phospholipids and signalling molecules.Triglycerides are used to store energy (as fat) and to transport fat around the body.
What is a phospholipid?
Phospholipids are a complex lipid that contains a fatty acid on carbons C-1 and C-2 of the glycerol, and a phosphate and head group on C-3. Depending on the head group, the phospholipid will be good for (basic) making membranes (including liposomes) or (neutral and acidic) signalling.
Outline three ways lipids are transported through aqueous environments
The first method of transport of lipids (FA’s) through aqueous environments is by binding to serum albumin.The other two methods are based on emulsification, however the details depend on the complexity of the lipid itself.Simple lipids utilise their amphiphilicity to produce single-layer MICELLES, which are spheres with the hydrophilic end of the FA on the outside, and the hydrophobic end on the inside, thereby allowing transport through aqueous environments.Complex lipids cannot produce a mono-layered sphere due to their multiple hydrophobic ends. As a result, they form a bilayer. As this gets bigger, it forms a spherical LIPOSOME, with a structure similar to a cell membrane, and a hydrophilic exterior.Both micelles and liposomes can accommodate proteins.
Briefly describe the three lipid storage/mobilisation pathways (Key Exam Question)
There are two pathways to lipid storage (either in the liver or in adipose tissue), and one to mobilisation. Interestingly, the liver acts as a scavenger in lipid metabolism, rather than the key role it plays in glucose metabolism.The EXOGENOUS pathway is the absorption pathway for lipids that are taken in through the diet. They are emulsified, and absorbed by the GI tract as chylomicrons. Necessary nutrients are taken up by peripheral tissue, with the remnants moving to the liver for storage.The ENDOGENOUS is a synthesis pathway for lipid storage. The liver converts chylomicrons and other lipids into VLDL, where they are transported through peripheral tissue. The peripheral tissue absorbs TAGs and FAs, leaving LDL, which carries cholesterol back to the liver.In both these pathways, HDL plays a key role in adding and removing apoproteins (to form LDL), extracting cholesteryl esters, and transporting cholesterol back to the liver.The MOBILISATION pathway starts with a stimulus, that leads to the release of adrenaline and glucagon. This signal hits the adipocytes, and activates HORMONE-SENSITIVE LIPASE, which hydrolises the FA’s from the TAG. The FA’s enter the bloodstream and bind to serum albumin, which delivers them to peripheral tissues for catabolism.
What are lipoproteins?
Lipoproteins are lipid transport vehicles synthesised by the body, in the liver and the GI tract. They have a mono-layer surface of phospholipids, apoproteins (APLs), and some cholesterol, and a centre composed mainly of TAGs and cholesteryl esters. The APLs are used for communication with receptors and to activate lipases if the body needs to mobilise lipid energy.
Outline the process of catabolism of Fatty Acids
Fatty acids are conjugated Acyl-CoA in the cytosol, in a very energy intensive reaction (smashes ATP to AMP). Acyl-CoA contacts carnitine-acyl transferase (CAT-1), which replaces the CoA with carnitine, forming acyl carnitine.The key regulation involves the CARNITINE SHUTTLE, an antiporter for acyl carnitine and carnitine across the mitochondrial membrane. Once in the mitochondria, acyl carnitine contacts CAT-2, which reforms it as acyl-CoA, liberating the carnitine for the CT.Acyl-CoA is catabolised through ß-oxidation in successive cycles of the ß-OXIDATION PATHWAY, which removes 2 C atoms, generating 1 Acetyl-CoA, 1 FADH2, 1 NADH, and 1 H+. A common, 18-C acyl chain will thus produce 9 acetyl CoA, 8 FADH2, 8 NADH, and 8H+ when fully ß-oxidised.
What are the two key regulations for lipid metabolism
Lipid metabolism is supply-regulated in two ways.1 - Hormone-sensitive lipase, which regulates the release of FAs from the Adipose tissue.2 - Carnitine shuttle, antiporter which regulates the passage of FAs across the mitochondrial membrane.
