Bioenergetics Explains the Structures of Membrane Lipids: Cholesterol, Plant Sterols, Unusual Fatty Acid Chains and Polyisoprenes

Abstract

All living membranes support cation gradients, which they maintain by cation pumps: proton pumps or -- for the animal plasma membrane -- sodium pumps. This includes the organelle membranes of the eukaryote. The negative side of the gradient faces the cells’ cytoplasm. Lipid bilayers leak both H+ and Na+ at rates that are equivalent in vivo (H+ is ∼10-5 cm/sec without a membrane potential([H+] is ∼10-7) whereas Na+ is ∼10-12 cm/sec without a membrane potential ([Na+] is ∼10-1). The resident membrane potential increases the rate of leakage. Cation leakage requires the cell to spend ATP energy pumping the cations back out. Resting cells spend 70 to 80% of their ATP on cation pumping. Cholesterol, found in animals, is the only lipid tested that inhibits Na+ leakage across phospholipid bilayers. It decreases leakage to 1/3 membranes w/o it. Meanwhile many membrane lipid structures inhibit H+ leakage by: 1) decreasing water diffusion through bilayers; 2) thickening the bilayer; 3) packing the bilayer cleavage with hydrocarbon. 1) sterols, hopanoids, tetrahymenol decrease membrane water permeability. 2) polyisoprenes, CoQ, squalene, dolichol, vitamin E., and carotenes thicken the membrane bilayer. 3) Iso- and anteiso-fatty acids, branched plant sterols, and chains in extreme acidophiles terminating with cyclohexane or cycloheptane groups. A unique phospholipid, cardiolipin (CL), displays a high pK2 (∼8.0) in bilayers. This appears to facilitate ATP synthesis in membranes that use the F0F¬1ATPase to make ATP. Except for the chloroplast with its CF0CF¬1ATPase, CL always accompanies the F0F¬1ATPase. In sum, membrane lipid structures are uniquely designed to support membrane bioenergetics. This makes the structures of membrane lipids as biochemically functional as are the structures of amino acids, nucleotides and carbohydrates are for proteins, nucleic acids and CHO polymers.