Carbohydrates, nucleotides, amino acids, now lipids

• Lipids exhibit diverse biological function– Energy storage– Biological membranes– Enzyme cofactors– Hormones– Intracellular signals– Etc.

Storage lipids

• Fatty acids are highly reduced carbon storage forms that can be oxidized to generate energy

• Common lipids derived from fatty acids include– Triacylglycerols– waxes

Fatty acids

• Carboxylic acids with hydrocarbon chains ranging from 4 to 36 carbons

• Can be saturated (no double bonds) or unsaturated (one or more double bonds)

• Nomenclature specifies the chain length and number of double bonds separated by a colon (position of double bond noted with a and superscript numbers)– Palmitic acid is abbreviated 16:0– Oleic acid is abbreviated 18:1

Patterns in commonly occurring fatty acids

• Even number of carbon atoms (result of using acetate as building blocks)

• Location of double bonds (in most monounsaturated fatty acids the double bond is between C9 and C10; in polyunsaturated fatty acids additional double bonds at C12 and C15 (some exceptions)

Physical properties of fatty acids

• Determined by length and degree of unsaturation– The longer the acyl chain and fewer the double

bonds, the lower the solubility in water

– Melting points lower for shorter/unsaturated fatty acids

• The carboxylic acid group is polar (ionized at neutral pH) and helps slightly in solubility

Storage to structural

Triacylglycerols

• Ester linked fatty acids with

a glycerol backbone

Can be “simple” where all

fatty acids are the same, but

often mixed

Triacylglycerols provide insulation and storage for energy • Hibernating animals generate a lot of

triacyglycerols under their skin

• Store carbon as triacylglycerols instead of glycogen and starch– A more reduced form of carbon, get more energy

(about twice) from oxidation– Hydrophobic character does not necessitate

carrying water weight (water used to hydrate carbohydrates)

Membrane lipids

• Are amphipathic, pack into bilayers

• Include:– Glycerophospholipids– Sphingolipids– Sterols

Glycerophospholipids

• Use glycerol 3-phosphate as backbone

• Two fatty acids attached via ester linkage to first and second carbons, a polar or charged group is attached via a phosphodiester linkage at the third carbon

Ether lipids

• Includes membrane structural lipids of the Archaea domain

Sphingolipids

• Have a polar head group and two nonpolar tails but contain sphingosine, not glycerol

• Carbons 1, 2, and 3 of sphingosine are analogous to glycerol carbons

• When a fatty acid is attached to the –NH2 group on C2, this compound is called ceramide

Subclasses of sphingolipids

• Sphingomyelins– Contain phosphocholine or phosphoethanolamine as

polar head group, prominent in myelin (hence the name)

• Glycosphingolipids– Modified with sugars; found in plasma membrane

(recall lectins)

• Gangliosides– Distinct carbohydrate pattern

Roles for sphingolipids

Phospholipases breakdown phospholipids

Sterols• Structural lipids found in most eukaryotic

membranes

• Also serve as precursors for various biomolecules

• Cholesterol

Other roles for lipids• Phosphatidylinositol regulates cell structure

and metabolism

• Serves as a binding site for specific proteins, and a source of extracellular messenger molecules

• Prostaglandins regulated synthesis of intracellular messenger cAMP

• Oxidized sterols (steroids) serve as hormones

• Quinones and vitamins E and K are oxidation-reduction cofactors

• Fat soluble vitamins serve as cofactors, and hormone precursors– Vitamin A (retinol) was discussed before in the context

of bacteriorhodopsin, and serves as a visual pigment

Getting energy from fat

• Oxidation of long-chain fatty acids to acetyl-CoA is another central energy generating pathway

• Electrons from this process pass to the respiratory chain, while acetyl-CoA produced during this process is further oxidized by the citric acid cycle

Fatty acids are activated and transported into the mitochondria

Distinct acyl-CoA synthetase

• Different enzymes have different substrate specificities for longer or shorter fatty acids

• All catalyze the formation of the thioester linkage between the fatty acid carboxyl group and thiol of Co-A coupled to ATP hydrolysis

• The reaction occurs in two steps as shown on previous slide

Carnitine as a carrier

• The fatty acyl group is transferred from CoA to carnitine, the resulting product is brought into the matrix via the acyl-carnitine/carnitine transporter

Linking pools of CoA

• The next step is transfer of the fatty acyl group from carnitine to mitochondrial CoA

• CoA in the mitochondrial is primarily used in oxidative degradation of pyruvate, fatty acids, and some amino acids

• Cytosolic CoA is also used in the biosynthesis of fatty acids

Transfer is rate-limiting

• The carnitine-mediated fatty acyl transfer is the rate-limiting step for oxidation of fatty acids and is a key regulatory point

• Once in the mitochondria, fatty-acyl CoA is quickly acted upon