Chemistry of lipid 3 _lipoprotein chemistry and prostaglandins.pptx

Editor's Notes

• #3: Lipids need to be transported in plasma to tissues and organs to perform their metabolic functions. Given the hydrophobic nature of the neutral fats (TG and cholesterol esters), lipid transport via plasma would not be possible without some form of hydrophillic adaptation. The lipids are transported by a series of micelles called lipoproteins, which consist of an outer monolayer of protein (apolipoprotein) and polar lipids (phospholipid and unesterified cholesterol). The inner core consists of the hydrophobic lipids which is the cholesteryl esters & TAG. Lipoproteins function both to keep their component lipids soluble as they transport them in the plasma, and also to provide an efficient mechanism for transporting their lipid contents and to (and from) the tissues. NB. In humans the transport system is less perfect than in other animals, that is why they experience a gradual deposition of lipid especially cholesterol in tissues (atherosclerosis).
• #22: Almost all mammalian cells except red blood cells produce prostaglandins and their related compounds, the prostacyclins, thromboxanes, leukotrienes and lipoxins, known collectively as eicosanoids since they are all C20 compounds; Greek: eikosi, twenty). The eicosanoids, like endocrine hormones, have profound physiological effects at extremely low concentrations. For example, they mediate the following: (1) the inflammatory response, notably as it involves the joints (rheumatoid arthritis), skin (psoriasis), and eyes; (2) the production of pain and fever; (3) the regulation of blood pressure; (4) the induction of blood clotting; (5) the control of several reproductive functions such as the induction of labor; and (6) the regulation of the sleep/wake cycle. The enzymes that synthesize these compounds and the receptors to which they bind are therefore the targets of intensive pharmacological research. The eicosanoids are also hormonelike in that they bind to G-protein-coupled receptors (Section 19-2B), and many of their effects are intracellularly mediated by cAMP. Unlike endocrine hormones, however, they are not transported in the bloodstream to their sites of action. Rather, these chemically and biologically unstable substances (some decompose within minutes or less in vitro) are local mediators (paracrine hormones; Section 19-1); that is, they act in the same environment in which they are synthesized.
• #24: Prostaglandins are all derivatives of the hypothetical C20 fatty acid prostanoic acid in which carbon atoms 8 to 12 form a cyclopentane ring (Fig. 25-66a). Prostaglandins A through I differ in the substituents on the cyclopentane ring (Fig. 25-66b):PGAs are ,-unsaturated ketones,PGEs are-hydroxy ketones, PGFs are 1,3-diols, etc. In PGF, the C9 OH group is on the same side of the ring as R1; it is on the opposite side in PGF.The numerical subscript in the namerefers to the number of double bonds contained on the side chains of the cyclopentane ring (Fig. 25-66c). In humans, the most prevalent prostaglandin precursor is arachidonic acid (5,8,11,14-eicosatetraenoic acid), a C20 polyunsaturated fatty acid that has four nonconjugated double bonds.The double bond at C14 is six carbon atoms from the terminal carbon atom (the carbon atom), making arachidonic acid an –6 fatty acid. As Sune Bergström and Bengt Samuelsson demonstrated, arachidonic acid is synthesizedsynthesized from the essential fatty acid linoleic acid (also an –6 fatty acid). This occurs via its desaturation with a 6- desaturase to yield -linolenic acid (GLA), followed by elongation and a second desaturation, this time with a 5- desaturase (Fig. 25-67; Section 25-4E). Prostaglandins with the subscript 1 (the “series-1” prostaglandins) are synthesized from dihomo--linolenic acid (DGLA; 8,11,14- eicosatrienoic acid), whereas “series-2” prostaglandins are synthesized from arachidonic acid. -Linolenic acid (ALA), another essential fatty acid since the 15-desaturase required for its synthesis occurs only in plants, is a precursor of 5,8,11,14,17-eicosapentaenoic acid (EPA) and the “series-3” prostaglandins. Since arachidonate is the primary prostaglandin precursor in humans, we shall mostly refer to the series-2 prostaglandins in our examples. Note, however, that when dietary linoleic acid and -linolenic acid are equally available, the relative activities of the 5- and 6- desaturases are important in determining the relative amounts of these prostaglandin precursors. Hvon Euler thought that these compounds originated in the prostate gland (hence their name) but they were later shown to be synthesized in the seminal vesicles.