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Biomedical subjects

H Brockerhoff

Publications and source records attributed to H Brockerhoff.

At least 55 records · Page 3Linked to original sources

Retention of a dialkylphosphatidylcholine in myelin and other membranes.

We describe an attempt to incorporate a metabolically inert phospholipid analog into animal membranes, especially myelin, in vivo, with the view of eventual long-term membrane modification or membrane engineering. A sonicated suspension of a mixture of [14C]phosphatidylcholine and its dialkyl analog, [3H] tetradecyloctadecano(1)phosphocholine, was injected into the brain of weanling rats. Samples were counted of whole brain, myelin, liver, and carcass, at intervals from 1 to 63 days, and the composition of the extracted lipid was determined by thin-layer chromatography. Both lipid labels were found to be cleared from the body at similar rates, but while phosphatidylcholine was metabolized within a day, with the label appearing mainly in the phosphatidylethanolamine fraction and in nonpolar lipids, the dialkylphosphatidylcholine remained intact, with retention in myelin of a small but almost constant amount for a month. Ways will have to be found to enhance uptake of the lipids by the brain.

Animals↗

Distribution of phosphoinositides among subfractions of rat brain myelin.

Rat brain myelin was separated into three subfractions, heavy, medium, and light, and the concentrations of phosphatidic acids (PA), phosphatidylinositol (PI), di- (DPI), and triphosphoinositide (TPI) in these fractions were determined. PI was evenly distributed among the fractions, and PA, DPI, and TPI occurred in highest concentrations in the "light" myelin. This result indicates that these fast metabolizing lipids play an important role in the tightly packed central lamellae of the myelin sheath.

Animals↗

Studies on the hydrogen belts of membranes: III. Glycerol permeability of dihydrosphingomyelin-cholesterol membranes.

The permeability of an N-oleoyldihydrosphingomyelin bilayer against glycerol was similar to that of a bilayer of phosphatidylcholine with identical effective hydrophobic chain length. Cholesterol at 1:1 molar ratio reduced the permeability, and also reduced the energy of activation of glycerol penetration, an effect not found for diesterphosphatidylcholine with cholesterol. The higher level of the ground state of the entropy of activation for permeability can be interpreted in terms of a hydrogen belt model which postulates lipid-lipid hydrogen bonding in membranes and explains the effect found as a disturbance of the hydrogen belt structure. Dihydrosphingomyelin can be considered to function as an "extender" in the hydrogen belt network.

Cholesterol↗

Leukocyte docosahexaenoic acid in juvenile form of ceroid-lipofuscinosis.

Leukocyte glycerolipid fatty acid compositions were determined in four patients of juvenile form of neuronal ceroid-lipofuscinosis (Battens disease), their parents and age-matched controls. A 54 to 93% reduction in docosahexaenoic acid (22:6, n-3) was noted in patient leukocytes. The parents also showed reduction in docosahexaenoic acid content, but to a lesser degree. The levels of linolenic family (n-6) polyunsaturated fatty acids were unchanged suggesting that the metabolic defect in this disease is specific to the linolenic family (n-3) of fatty acids.

Adolescent↗

Studies on the hydrogen belts of membranes: I. Diester, diether, and dialkyl phosphatidycholines and polyoxyethylene glycerides in monolayers with cholesterol.

The hydrogen belts of membranes are defined as the regions consisting of hydrogen bond acceptors, i.e., the C=O groups of glycero- and sphingolipids, and hydrogen bond donors, i.e., cholesterol-OH, sphingolipid-OH, proteins, and water. Lipid-lipid hydrogen bonding in these belts has been suggested. The connection of such hypothetical bonding with the condensation effect, i.e., the apparent reduction of surface area occupied by phospholipids in mixed monolayers with cholesterol, has been tested with lipids possissing and lacking C=O groups: diester, diether, and dialkyl phosphatidylcholine, and analogous polyoxyethylene diglycerides. Condensation by cholesterol was observed for all lipids. Consequently, the hypothetical lipid-C=O-cholesterol hydrogen bonding is not a prerequisite for the condensation effect.

Cholesterol↗

Studies on the hydrogen belts of membranes: II. Non-electrolyte permeability of liposomes of diester, diether, and dialkyl phosphatidylcholine and cholesterol.

We have postulated the existence of lipid-lipid and protein-lipid hydrogen bonding in the hydrogen belts of membranes, i.e., the regions of hydrogen bond acceptors (carbonyl oxygens of esters and amides) and hydrogen bond donors (hydroxyls of cholesterol, sphingosine, proteins, water). To assess the possible effects of modifications of the hydrogen belts on membrane permeability, we prepared a diester phosphatidylcholine and two analogs lacking carbonyl oxygens, a diether and a dialkyl phosphatidylcholine, care being taken to synthesize lipids of identical efficient hydrophobic chain length. Relative permeation rates for glycerol and urea were determined by osmotic swelling of liposomes containing the phospholipids alone or with an equimolar quantity of cholesterol, with 4 mole % of dioleylphosphate added. The permeation rates of both solutes were similar for all three lipids, with Arrhenius activation energies deltaE* around 16 kcal/mole. Cholesterol reduced the permeability of all three membranes. The activation energy deltaE* of permeation did not change for diester and dialkyl phosphatidylcholine with cholesterol, but was lower by about 5 kcal/mole for the diether lipid with cholesterol. This corresponds to a reduction in the entropy of activation deltadeltaS*approximately-16 cal/mole/degree. We interpret the results as supporting the hypothesis of interaction between cholesterol hydroxyl and phospholipid carbonyl.

Cholesterol↗