Types of lipids Chemistry 256

Lipids Basically, any biologically interesting nonpolar molecule Thus they are primarily hydrocarbons, with some (few) functional groups Generally built from small molecules such as acetyl-CoA or isoprene (below)

Fatty acids – generally, even-numbered carbon chains x:y notation indicates x carbons with y unsaturations  z notation indicates double bond at the z-carbon  -n notation indicates unsaturation at the nth carbon from the methyl end Double-bond orientations always cis (puts 60° kink in chain).

Fatty acid properties More unsaturation = lower melting point (fewer London interactions to overcome due to the kinks in the chain) Longer chain = higher melting point (more London interactions to overcome)

Triacylglycerols = triglycerides main components of fats (solid) and oils (liquids)

To make a triacylglycerol Condense three fatty acids (they do not need to be the same fatty acid) onto the alcohol groups of glycerol. Biodiesel, for instance, has this structure. Energy storage

Glycerophospholipids = phosphoglycerides, key membrane component X = H (phosphatidic acid), CH 3 CH 2 NH 3 + (phosphatidyl- ethanolamine), CH 3 CH 2 N(CH 3 ) 3 + (phosphatidyl- choline)

Polarity in glycerophospholipids Note the “head” group (i.e., the phospho-X group) is charged, though overall neutral. This lends polarity to an otherwise fairly non- polar molecule

Phospholipases hydrolyze glycerophospholipids, release fatty acids Problem: How does a nonpolar substrate get anywhere near a (polar) enzyme for a reaction to take place?

One strategy that is found with phospholipase A 2 is for the phosphate group head to interact deep in the active site, and the hydrophobic tail kept in place by hydrophobic interactions with side chain aromatic groups. (Barden, Darke, Deems and Dennis “Interaction of phospholipase A2 from cobra venom with Cibacron Blue F3GA” (1980) Biochemistry 19)

Plasmalogens have an ether linkage. Function of these molecules is not well- understood, though there is some evidence that they react with free radicals that prevents myelinization of nerves (for instance, see Gorgas, Teigler, Komljenovic and Just, “The ether lipid-deficient mouse: tracking down plasmalogen functions” (2006), Biochimica et Biophysica Acta 1763).

Sphingolipids are amino alcohols – note the amide in R 2 and vinyl group in R 3 Named in the 1920s, when Egyptology was all the rage (“Sphinx” = mysterious) and these compounds were discovered and their function not known at the time Now known to have many functions, including nerve cell sheaths (electrical insulation), cell-cell recognition The sphingomyelin shown is a type of sphingolipid called a ceramide.

Sphingolipids can be quite complex - a ganglioside has an oligosaccharide attached

Steroids – structure unlike the other lipids; basically, four fused rings, roughly planar

Steroid carbon numbering system The fused ring system is lettered A, B, C, D as shown Numbering of carbons starts on ring A; C-18 is always a methyl off C- 13, C-19 is always a methyl off C-10, and C- 20 on up is always off of C-17 Sterol alcohol is always on C-3

Steroid synthetic history Adolf Butenandt and G. Hamish (1935) “A method for preparing testosterone from cholesterol” was the first synthesis of a steroid hormone

Steroid functions – mostly a eukaryote thing Cholesterol changes fluidity of a membrane Glucocorticoids are stress hormones regulating metabolism Mineral corticoids regulate excretion by kidneys Androgens and estrogens regulate sexual development and function

Isoprenoids = terpenoids, contain isoprene units Functions as diverse as pigments (beta- carotene), vitamins (retinol = vitamin A), pheromones

In fact, when organisms decompose, isoprene and isoprenoid units are some of the most abundant compounds generated (Wallach, 1887). Fossil fuels (petroleum and coal) contain a great number of isoprenoids.

Eicosanoids = icosanoids, which are mostly prostaglandins Word derived from “eikos” = twenty; these compounds are derived from twenty-carbon fatty acids “Local” hormones, work at or near site they were made and then are rapidly degraded Key to inflammation and pain response

The first prostaglandins were discovered by Ulf von Euler (Karolinska Institute, Stockholm) in 1935; he won the Nobel Prize in Medicine in Prostaglandins work at very low concentrations. pain fever inflammation