Lipids And Lipid Metabolism Flashcards
Define lipid and Lipidology
Lipids are defined as organic compounds that are poorly soluble in water but soluble in organic solvents.
▪Lipidology is the study of abnormal lipid metabolism. An understanding of the pathophysiology of plasma lipid metabolism is usefully based on the concept of lipoproteins, the form in which lipids circulate in plasma.
Classification into 3 groups on the basis of the products released on hydrolysis.
(1) simple lipids e.g. waxes and triacylglycerols (triglycerides).
(2) compound or complex lipids e.g. phospholipids (PL) and glycolipids found in biological membranes.
(3) derived or polyprenyl lipids e.g. fat-soluble vitamins A and D, steroids (e.g. cholesterol), and some of its hormone derivatives such as aldosterone, testosterone, and oestrogen.
Classification into 5 groups based on chemical structure
(1) Fatty acids: straight-chain carbon compounds of varying lengths. E.g., Short (2-4 carbon atoms), Medium (6-10 carbon atoms) and long chain (12-26 carbon atoms). E.g., Oleic, Linoleic, Stearic, Prostaglandins, etc.
(2) Glycerol ester: E.g., Triglycerides, Phosphogylcerides
(3) Sterol derivatives: E.g., Cholesterol & Cholesteryl esters, Steroid hormones, Bile acids, Vitamin D
(4) Sphingosine derivatives: E.g., Sphingomyelin, glycosphingolipids (5) Terpenes (Isoprene polymers): E.g., Vitamins A, E and K
(5) Terpenes (Isoprene polymers): E.g., Vitamins A, E and K
Classification into 4 groups based on clinical interest (major forms of lipid present in plasma) are
- fatty acids,
- triglycerides,
- cholesterol and 4. phospholipids.
They are of clinical interest because of their roles in the development of deposits in arteries, called atheromas, which are associated with heart disease, strokes, and peripheral vascular disease.
Fatty acids
These are mostly straight-chain monocarboxylic acids of varying lengths.
They are mainly derived from dietary or tissue triglyceride, but the body can also synthesise most of them, apart from certain polyunsaturated (essential) fatty acids.
Fatty acids can esterify with glycerol to form triglycerides or be non-esterified or free (NEFAs).
They also act as an alternative or additional energy source to glucose.
Triglycerides
Triglycerides: These are fatty acid esters of glycerol, and are the main lipids in the diet.
◦ Most of these exogenous triglycerides pass into plasma as chylomicrons.
◦ Endogenous triglyceride synthesis occurs in the liver from fatty acids and glycerol. The triglycerides synthesised in this way are transported as very low density lipoprotein (VLDL).
◦ Plasma triglyceride concentrations rise after a meal, unlike that of plasma cholesterol.
Describe Phospholipids
They are complex lipids, are mainly synthesised in the liver and small intestine, similar in structure to triglycerides but containing phosphate and a nitrogenous base in place of one of the fatty acids.
They fulfil an important structural role in cell membranes, and the phosphate group confers solubility (a characteristic detergent property) on non-polar lipids (fatty acid) and cholesterol in lipoproteins.
Cholesterol
Cholesterol is a steroid found exclusively in animals and present in virtually all cells and body fluids. It is a precursor of numerous physiologically important steroids, including bile acids and steroid hormones.
It is present in the diet and also synthesised in the liver and small intestine, the rate-limiting step being catalysed by HMG-CoA reductase. (See cholesterol synthetic pathways)
About two-thirds of the plasma cholesterol is esterified with fatty acids to form cholesterol esters.
BIOLOGIC FUNCTIONS of lipids
- source of metabolic fuel and energy storage (triglyceride)
- serving as hormones or precursors of hormones & bile acids
(cholesterol) - acting as functional and structural components in cell membranes (cholesterol and phospholipids)
- forming insulation to allow nerve conduction or to prevent heat loss
- important in digestion (fat-soluble vitamins, bile acids)
LIPOPROTEINS
This is a lipid-protein complex which makes it possible for lipid transportation.
Because lipids are relatively insoluble in aqueous media, they are transported in body fluids as, often spherical, soluble protein complexes called lipoproteins. The exception are fatty acids which are transported bound to albumin.
The water-soluble (polar) groups of proteins, phospholipids and free cholesterol face outwards and surround an inner insoluble (non-polar) core of triglyceride and cholesterol esters.
Apolipoproteins and their physiologic function
Apolipoproteins: These are the protein components of the lipoproteins. They are a complex family of polypeptides that promote and control lipid transport through the circulation and lipid uptake into tissues.
They have 3 major physiologic functions:
1. activating important enzymes in the lipoprotein metabolic pathways,
- maintaining the structural integrity of the lipoprotein complex, and
- facilitating uptake of lipoprotein into cells through their recognition by specific cell surface receptors.
APOLIPOPROTEINS separable into 4 main groups
They are(Apo A, B, C and E) and apo(a).
- ApoA is synthesized in the liver and intestine. It is initially present in chylomicrons in lymph, but rapidly transfers to HDL. Present in plasma in 2 main forms; ApoA1 and ApoA2.
- ApoB is present in plasma in 2 forms, apoB100 and apoB48. ApoB 100 is the protein component of LDL, and is also present in chylomicrons, VLDL and IDL. ApoB48 (the N-terminal half of apoB100) is only found in chylomicrons. ApoB 100 is recognised by
specific receptors in peripheral tissues. - ApoC. This family of proteins (apoC1, apoC2 and apoC3) is synthesized in the liver and incorporated into HDL.
- ApoE is synthesized in the liver, incorporated into HDL and transferred in the circulation to chylomicrons and VLDL. There are 3 major isoforms (apoE2, apoE3 and apoE4). ApoE is probably mainly involved in the hepatic uptake of chylomicron remnants and IDL; it binds to apoB receptors in the tissues.
- Apo(a) is present in equimolar amounts to apoB 100 in Lp(a). It has a high carbohydrate content and has a similar amino acid sequence to plasminogen.
LIPOPROTEIN METABOLISM consists of the following processes
These processes include:
1. transfer of apolipoproteins between lipoproteins
- transfer of lipids between lipoproteins e.g. cholesterol ester transfer protein (CETP)
- metabolism of lipid content by enzymatic action: hydrolysis of TG by lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTL), and esterification of free cholesterol by lecithin cholesterol acyltransferase (LCAT)
- clearance of lipoproteins from the plasma via receptors, mainly by the liver.
The operation of these different processes can be conceptualised as 3 interconnected cycles or pathways of lipid transport:
- exogenous cholesterol transport for delivery of dietary lipids to the tissues
- endogenous cholesterol transport for delivery of hepatic lipids to the tissues
- reverse cholesterol transport for return of excess cholesterol from the tissues to the liver.
Chylomicron metabolism
- Chylomicrons are formed in the intestinal mucosa after a fat‐containing meal, and reach the systemic circulation via the thoracic duct.
- They then transfer apoA to HDL and acquire apoC and apoE from HDL.
- The apoC‐II activates lipoprotein lipase in the tissues,
- and triglycerides are progressively removed from the hydrophobic core of the chylomicrons. As the size of the particles decreases, the more hydrophilic surface components (apoC, unesterified cholesterol and phospholipid) transfer to HDL.
- The triglyceride‐poor chylomicron remnants are taken up by the liver, where they are catabolised.
