Thematic review series: brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal.

Lipid composition of the normal human brain: gray matter, white matter, and myelin

Lipids of nervous tissue: composition and metabolism.

Among the variant forms of G6PD known are many with altered electrophoretic mobility or kinetic properties but normal activity. With other mutations of the X-chromosomal genes which control the structure of this enzyme the activity is diminished. The most severe loss of activity is seen in those rare individuals who have chronic nonspherocytic hemolytic anemia due to G6PD deficiency. Although the total number of individuals with this form of G6PD deficiency is small, even among them a large number of different mutant forms of the enzyme have been identified. It is almost true to say that each affected family has its crwn private mutant enzyme. In contrast to this state of affairs, two mutations which cause moderate loss of enzyme activity have become established at high frequency in certain races. The Negro variant of G6PD deficiency, which retains about 10 to 20 per cent to the normal level of enzyme activity, reaches high frequencies in African and U. S. Negroes (5 to 25 per cent of males). In the form of G6PD deficiency found in Sephardic Jews, and in Greeks and Sardinians, enzyme activity of the red blood cell is reduced to about 5 per cent of normal, and this, too, is common. It is generally presumed that these two mutants have reached their present high frequency because they confer some selective advantage upon the heterozygous female, which balances any disadvantages which exists for the hemizygous male or the homozygous female. These diverse forms of G6PD deficiency may serve as a useful guide for future studies of inborn errors of metabolism and other recessively inherited diseases. Recessively inherited conditions which are rare may turn out to be heterogeneous, in that a number of mutant alleles may exist at the gene locus concerned. No mutant has

Inborn errors of metabolism

/pdf/metabolism-and-physiological-significance-of-lipids-4ql1d9my66.pdf

Metabolism and Physiological Significance of Lipids

ELECTRON microscopic studies have shown that the myelin sheath is composed of a compact ordered arrangement of unit membranes (FINEAN, 1957 ; ROBERTSON, 1959, 1964). Myelin therefore provides a particularly suitable model for the investigation of the molecular organisation of biological membranes. However, until quite recently it was not possible to isolate myelin from nervous tissue and reliable information about its chemical composition was not available. Improved methods for the separation of subcellular structures have now been applied to neural tissue and a number of laboratories have described techniques for the isolation of myelin in a form suitable for direct analysis (WHITTAKER, 1959; PATTERSON and FINEAN, 1961 ; AUGUST, DAVISON and WILLIAMS, 1961 ; LAATSCH, KIES, GORDON and ALVORD, 1962; DAVISON and GREGSON, 1962; HULCHER, 1963). Some reports of the lipid composition of myelin from individual species have already appeared (PATTERSON and FINEAN, 1961 ; NUSSBAUM, BIETH and MANDEL, 1963; AUTILIO, NORTON and TERRY, 1964; EICHBERG, WHITTAKER and DAWSON, 1964; SEMINARIO, HREN and GOMEZ, 1964; CUZNER, DAVISON and GREGSON, 1965). Although it has been suggested that all membranes may have a common ‘unit membrane’ structure (ROBERTSON, 1964) both electron microscopic and biochemical evidence indicate that the various membranes found in the cell are not necessarily similar in all properties (STOECKENIUS, 1964). Earlier work from this laboratory has indicated that mammalian myelin may represent a unique class of membrane for it has a characteristically slow rate of turnover with little associated enzyme activity (ADAMS, DAVISON and GREGSON, 1963). In addition indirect evidence led to the idea that the lipid composition of myelin also differs from that of other membranes (ROSSITER, 1962; ADAMS and DAVISON, 1965; GREGSON 1965). The purpose of the present work has been to investigate this possibility more thoroughly by comparing the chemical composition of myelin with that of another cell membrane fraction from the same tissue. Myelin and microsomal fractions have been prepared therefore from the brains of a number of mammalian and more primitive vertebrates ; samples have been examined by electron microscopy and submitted to chemical analysis. The results of these and earlier observations will be discussed with particular reference to the possible molecular organisation of membranes. EXPERIMENTAL Materiais. The following animals were used in the present work: white Wistar rats, rabbits, the feral pigeon, common frog (Rana temporaria) and dogfish (Scyllium cuniculu). These animals were killed, exsanguinated and the brain removed. Ox brain, collected in ice from the slaughter house, and human frontal cerebral cortex obtained at autopsy, were brought to the laboratory and white matter removed. Human brains were obtained from patients who had died from non-neurological causes.

The chemical composition of vertebrate myelin and microsomes

RADIOACTIVE cholesterol has been shown by DAWN, DOBB~G, MORGAN and PAYLING WRIGHT (1958, 19594 to be incorporated in the central nervous system when it is administered to immature animals and to remain in that organ for mom than a year. These investigations have now been extended to a similar study (DAVQOU, MORGAN, WAJDA and PAYLING WRIGHT, 1959b) in which [3-\"C]serine has been used as the metabolic precursor of sphingolipids and other lipid components of the myelin sheath. The present paper describes and evaluates the methods needed in that study for the quantitative separation of the individual lipids from the crude brain extract. It further records some observations on their dsering rates of deposition in the central nervous system of rabbits during growth.

Metabolism of myelin lipids: estimation and separation of brain lipids in the developing rabbit

The brain differs from other organs in that dynamic metabolism of total lipids is restricted in the former in comparison to the rest of the body. Previous investigators (Davison & Dobbing, 1960a, b; Davison, Morgan, Wajda & Payling Wright, 1959) have shown, by introduction of radioactive precursors into developing anini’als, that part of the brain lipids remained metabolically stable during growth and subsequently in the adult animal. It was further suggested that this metabolic stability was associated with the myelin sheath and possibly other anatomical structures in the brain. Evidence in support of this concept has recently been reviewed (Davison, 1964).

Chemical and metabolic studies of rat myelin of the central nervous system.

IN an investigation into the cerebral lipids from a number of cases of multiple sclerosis CUMINGS (1953, 1955) found that apparently normal areas of the brain were deficient in phospholipids. This important observation suggests that patients with the disease might have a generaliscd deficiency of brain lipid and therefore a predisposition to multiple sclerosis (THOMPSON, 1961). The present study was undertaken in an attempt to confirm and extend the original observations of CUMINGS on the lipid composition of apparently normal areas of brain from patients with multiple sclerosis. In the first stage of this work modern techniques for the extraction and isolation of lipids were used for the complete analysis of normal human brain lipids (DAVISON and WAJDA, 1962). These same methods have now been used for determining the brain lipid composition in five cases of multiple sclerosis.

Cerebral lipids in multiple sclerosis.

Although values for the lipid content of human cerebral grey and white matter have been compiled by several authors (e.g. LeBaron & Folch, 1957; Mcllwain, 1959; Deuel, 1951) much of this information has been obtained by older methods and only a few workers have reported lipid analyses on the same brain samples (Brante, 1949; Johnson, McNabb & Rossiter, 1949; Cumings, 1953, 1955). The purpose of this paper is to describe a simple technique for the complete analysis of the major brain lipids and to record the results obtained by this method for fresh and formalin-fixed human grey and white matter. The present method is based on a preliminary separation of a washed protein-free chloroformmethanol extract of nervous tissue on an alumina colunm (Long & Staples, 1959, 1960, 1961; Rhodes & Lea, 1957; Davison & Wajda, 1959) with subsequent analysis of the original extract and each separated fraction by simple chemical procedures or by chromatography on paper. The method has been used for the analysis of samples of 50 mg. wet wt. or more of nervous tissue and also for the estimation of brain lipids labelled with radioactive isotopes.

/pdf/analysis-of-lipids-from-fresh-and-preserved-adult-human-rx79d6gyao.pdf

Analysis of lipids from fresh and preserved adult human brains.

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