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

Table 10-1

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 acylcarnitine/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