Lipids of nervous tissue: composition and metabolism

As indicated in the Introduction, the many significant developments in the recent past in our knowledge of the lipids of the nervous system have been collated in this article. That there is a sustained interest in this field is evident from the rather long bibliography which is itself selective. Obviously, it is not possible to summarize a review in which the chemistry, distribution and metabolism of a great variety of lipids have been discussed. However, from the progress of research, some general conclusions may be drawn. The period of discovery of new lipids in the nervous system appears to be over. All the major lipid components have been discovered and a great deal is now known about their structure and metabolism. Analytical data on the lipid composition of the CNS are available for a number of species and such data on the major areas of the brain are also at hand but information on the various subregions is meagre. Such investigations may yet provide clues to the role of lipids in brain function. Compared to CNS, information on PNS is less adequate. Further research on PNS would be worthwhile as it is amenable for experimental manipulation and complex mechanisms such as myelination can be investigated in this tissue. There are reports correlating lipid constituents with the increased complexity in the organization of the nervous system during evolution. This line of investigation may prove useful. The basic aim of research on the lipids of the nervous tissue is to unravel their functional significance.

Preparation, properties and metabolism of retinoic acid anhydride.

A new analogue of vitamin A, viz., retinoic acid anhydride was prepared, for the first time, by the action of thionyl chloride on retinoic acid in benzene containing pyridine. The amhydride was charcterised by its chromatographic properties, elemental analysis, ultraviolet absorption, infrared and nuclear magnetic resonance spectral characteristics. The compound could be readily hydrolysed to retinoic acid both by acid and alkali treatments and reduced by lithium aluminium hydride to vitamin A alcohol (retinol). The spectral changes with antimony trichloride reagent were similar to those observed for retinoic acid. The metabolism of retinoic acid anhydride was found to be similar to that of retinoic acic. When administered either orally or intraperitoneally, the compound promotes growth in vitamin A-deficient rats. Time-course experiments revealed that retinoic acid anhydride is converted into retinoic acid by non-enzymatic hydrolysis and thereby exerts its biological activity. The biopotency of the anhydride was found to be nearly the same as that of the acid. A new method of preparing esters of retinoic acid employing retinoic acid anhydride as an intermediate, has been described.

Hormones and Cuscuta development: IAA uptake transport and metabolism in relation to growth in the absence and presence of applied cytokinin

Transport of 1-14C-IAA in successive stem segments of Cuscuta was strictly basipetal in growing and non growing regions of the vine with a flux velocity of 10-12 mm/h (intercept method). This transport showed a distinct peaked profile, increasing from a low value at 10 mm from the apex to a maximum between 50 and 90 mm before declining to a low value again around 160 mm at which elongation growth ceased. The IAA transport profile paralleled the in vivo growth rate profile, though the latter peaked ahead of transport. A better correlation was observed between the profile of growth responsiveness of the vine to exogenous IAA application and the profile of IAA transport. Growth responsiveness was determined as the differential in growth rate of stem segments in vitro in the absence and presence of growth optimal concentration of IAA (10 μm). Retention of exogenous IAA in the stem was maximal where transport decreased, and this coincided with the region of maximal conjugation of applied 1-14C-IAA to aspartic acid to form indoleacetylaspartate (IAAsp). In addition to aspartate, IAA was conjugated to a small extent to an unidentified compound. IAA destruction by decarboxylation was greatest where transport was low, particularly in the nongrowing region, where lignification occurred (i.e., beyond 180 mm). At concentrations up to 20 μM, a pulse of 1-14C-IAA chased by "cold" IAA moved as a peak (with a peak displacement velocity of 12-18 mm/h) in the "growth" region of the vine, but became diffusionlike where growth either fell off steeply or ceased. At a higher (50 μM) IAA concentration, though uptake was not saturated, transport in the growth region became diffusionlike, indicating saturation of the system. Reduced IAA flux in the region where growth responsiveness to IAA declined coincided with the region of increased IAA conjugation. However, it cannot be concluded whether increased IAA conjugation was the cause or effect of decreased IAA flux. Application of benzyladenine to the vines in vivo, a treatment that elicited haustoria formation by 72 h, resulted in the inhibition of both IAA transport and elongation growth rate in the subapical region. In vitro treatment of vine segments with BA similarly increased IAA retention and decreased IAA transport. IAA loss was suppressed, and conjugation to IAAsp was enhanced. © 1989 Springer-Verlag New York Inc.

Thyroidal control of hepatic release and metabolism of vitamin A

The inverse relationship that exists between thyroxine and the vitamin A level of plasma has been examined in chicken. Thyroxine treatment leads to a decrease in the level of vitamin A carrier proteins, retinol-binding protein and prealbumin-2 in plasma and liver. There is an accumulation of vitamin A in the liver, with a greater proportion of vitamin A alcohol being present compared to that of control birds. In thyroxine treatment there is enhanced plasma turnover of retinol-binding protein and prealbumin-2, while their rates of synthesis are marginally increased. Amino acid supplementation partially counteracts effects of thyroxine treatment. Amino acid supplementation of thyroxine-treated birds does not alter the plasma turnover rates of retinol-binding protein and prealbumin-2 but increases substentially their rates of synthesis. The release of vitamin A into circulation is interfered with in hyperthyroidism due to inadequate availability of retinol-binding protein being caused by enhanced plasma turnover rate not compensated for by synthesis.

Absorption, translocation and metabolism of fluchloralin in groundnut (Arachis hypogaea) and pigweed (Amaranthus viridis)

Root absorption and translocation of [C-14]fluchloralin were determined in groundnut (Arachis hypogaea L.) cv. TMV-2 and pigweed (Amaranthus viridis L.) grown in nutrient solution culture under greenhouse conditions. Root-applied fluchloralin toxicity to groundnut and pigweed was also examined. A growth reduction of 50% occurred in groundnut that received fluchloralin at a concentration of 9.0 mum. Root absorption was similar for both groundnut and pigweed at one day after application (DAA), but groundnut absorbed about twice the amount of fluchloralin during 4 and 8 days of continuous application, compared with pigweed. Groundnut absorbed 25% of the total applied fluchloralin after 8 days. Translocation to leaves from treated roots was low and roots of groundnut contained 80% of the total absorbed C-14, 8 DAA. Contrary to the observations in groundnut, transport from the roots and leaves following root application in pigweed was rapid: 1 and 8 DAA, leaves of pigweed contained 45 and 70% of the total absorbed C-14, respectively. Different patterns of fluchloralin metabolism were observed in pigweed and groundnut. Pigweed metabolized most of the fluchloralin absorbed by roots. The fluchloralin tolerance of pigweed could partially be accounted for by absorption, translocation and metabolism.

Variation at Diabetes- and Obesity-Associated Loci May Mirror Neutral Patterns of Human Population Diversity and Diabetes Prevalence in India

South Asian populations harbor a high degree of genetic diversity, due in part to demographic history. Two studies on genome-wide variation in Indian populations have shown that most Indian populations show varying degrees of admixture between ancestral north Indian and ancestral south Indian components. As a result of this structure, genetic variation in India appears to follow a geographic cline. Similarly, Indian populations seem to show detectable differences in diabetes and obesity prevalence between different geographic regions of the country. We tested the hypothesis that genetic variation at diabetes-and obesity-associated loci may be potentially related to different genetic ancestries. We genotyped 2977 individuals from 61 populations across India for 18 SNPs in genes implicated in T2D and obesity. We examined patterns of variation in allele frequency across different geographical gradients and considered state of origin and language affiliation. Our results show that most of the 18 SNPs show no significant correlation with latitude, the geographic cline reported in previous studies, or by language family. Exceptions include KCNQ1 with latitude and THADA and JAK1 with language, which suggests that genetic variation at previously ascertained diabetes-associated loci may only partly mirror geographic patterns of genome-wide diversity in Indian populations.

Uncoupling Protein 2 and 3 Gene Polymorphisms and Their Association with Type 2 Diabetes in Asian Indians

Background: This study examined the association of -866G/A, Ala55Val, 45bpI/D, and -55C/T polymorphisms at the uncoupling protein (UCP) 3-2 loci with type 2 diabetes in Asian Indians. Methods: A case-control study was performed among 1,406 unrelated subjects (487 with type 2 diabetes and 919 normal glucose-tolerant NGT]), chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in Southern India. The polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Haplotype frequencies were estimated using an expectation-maximization algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. Results: The genotype (P = 0.00006) and the allele (P = 0.00007) frequencies of Ala55Val of the UCP2 gene showed a significant protective effect against the development of type 2 diabetes. The odds ratios (adjusted for age, sex, and body mass index) for diabetes for individuals carrying Ala/Val was 0.72, and that for individuals carrying Val/Val was 0.37. Homeostasis insulin resistance model assessment and 2-h plasma glucose were significantly lower among Val-allele carriers compared to the Ala/Ala genotype within the NGT group. The genotype (P = 0.02) and the allele (P = 0.002) frequencies of -55C/T of the UCP3 gene showed a significant protective effect against the development of diabetes. The odds ratio for diabetes for individuals carrying CT was 0.79, and that for individuals carrying TT was 0.61. The haplotype analyses further confirmed the association of Ala55Val with diabetes, where the haplotypes carrying the Ala allele were significantly higher in the cases compared to controls. Conclusions: Ala55Val and -55C/T polymorphisms at the UCP3-2 loci are associated with a significantly reduced risk of developing type 2 diabetes in Asian Indians.

Analysis of proteins with the `hot dog' fold: Prediction of function and identification of catalytic residues of hypothetical proteins

Background: The hot dog fold has been found in more than sixty proteins since the first report of its existence about a decade ago. The fold appears to have a strong association with fatty acid biosynthesis, its regulation and metabolism, as the proteins with this fold are predominantly coenzyme A-binding enzymes with a variety of substrates located at their active sites. Results: We have analyzed the structural features and sequences of proteins having the hot dog fold. This study reveals that though the basic architecture of the fold is well conserved in these proteins, significant differences exist in their sequence, nature of substrate and oligomerization. Segments with certain conserved sequence motifs seem to play crucial structural and functional roles in various classes of these proteins. Conclusion: The analysis led to predictions regarding the functional classification and identification of possible catalytic residues of a number of hot dog fold-containing hypothetical proteins whose structures were determined in high throughput structural genomics projects.