Disorders of glucose metabolism in sleep apnea.

Sleep is a complex behavioral state that occupies one-third of the human life span. Although viewed as a passive condition, sleep is a highly active and dynamic process. The sleep-related decrease in muscle tone is associated with an increase in resistance to airflow through the upper airway. Partial or complete collapse of the airway during sleep can lead to the occurrence of apneas and hypopneas during sleep that define the syndrome of sleep apnea. Sleep apnea has become pervasive in Western society, affecting approximately 5% of adults in industrialized countries. Given the pandemic of obesity, the prevalence of Type 2 diabetes mellitus and metabolic syndrome has also increased dramatically over the last decade. Although the role of sleep apnea in cardiovascular disease is uncertain, there is a growing body of literature that implicates sleep apnea in the pathogenesis of altered glucose metabolism. Intermittent hypoxemia and sleep fragmentation in sleep apnea can trigger a cascade of pathophysiological events, including autonomic activation, alterations in neuroendocrine function, and release of potent proinflammatory mediators such as tumor necrosis factor-alpha and interleukin-6. Epidemiologic and experimental evidence linking sleep apnea and disorders of glucose metabolism is reviewed and discussed here. Although the cause-and-effect relationship remains to be determined, the available data suggest that sleep apnea is independently associated with altered glucose metabolism and may predispose to the eventual development of Type 2 diabetes mellitus.     

Chiasma-induction and tyrosine metabolism in locusts

The production of a gregarization pheromone has been postulated in locusts, with effects on melanization of the hopper cuticle and increased chiasma frequency during meiosis in the adult on crowding or gregarization. Lack of chiasma-inducing effect of the pheromone on albino strains is correlated with the absence or deficiency of some of the products of the metabolic pathways of tyrosine. Some of these products, commercially obtainable, are the amino acids phenylalanine and tyrosine leading to both the melanization and sclerotization pathways; dopamine formed from dopa in the lastnamed pathway; three products of dopamine i.e. protocatechuic acid, noradrenaline and adrenaline. The injection of solutions of these metabolites into the haemolymph of solitary hoppers has shown that only dopa to some extent but noradrenaline to a large extent are effective in raising chiasma frequency in solitarised individuals of normal-coloured strains of Locusta, while in two albino strains, which differ genetically, the injection of dopa, dopamine, protocatechuic acid and noradrenaline proved effective; phenylalanine was effective in only one of these albino strains, while adrenaline was effective in neither. The chiasma-inducing effect of noradrenaline, common to the three strains, is accompanied in the normal-coloured strain by a greater retention of dark coloration during solitarization and by some attainment of the crowded type of morphometric ratios which is a third physical criterion of gregarization. The genetic blocks to the physical criteria of gregaria in the albino strains lie at the immediate level of dopa production or previous to this reaction; it may be construed that such a block in the solitaria of normal-coloured strains also lies at this early level, in this case being induced by too low a pheromone concentration.     

Phenylalanine and tyrosine metabolism in the facultative methylotroph Nocardia sp. 239

Nocardia sp. 239 is able to use l-tyrosine and both d- and l-phenylalanine as carbon-, energy- and nitrogen sources for growth. The catabolism of these compounds is by way of (4-hydroxy)phenylpyruvate and (4-hydroxy)-phenylacetate as intermediates and the pathways merge at the level of homogentisate. The conversion of the amino acids into (4-hydroxy)phenylpyruvate is catalyzed by an inducible NAD-dependent phenylalanine dehydrogenase and l-tyrosine aminotransferase, respectively. Incubation of the organism in media with l-phenylalanine plus phenyl-pyruvate resulted in diauxic growth, with phenylpyruvate used first. Phenylalanine dehydrogenase activity cold only be detected after depletion of phenylpyruvate, in the ensuing second growth phase on l-phenylalanine. During growth on phenylalanine plus methanol, low levels of phenylalanine dehydrogenase were detected and this resulted in simultaneous utilization of the two substrates. Following diepoxyoctane treatment, mutants of Nocardia sp. 239 affected in phenylalanine and phenylpyruvate degradation were isolated. Double mutants blocked in both phenylalanine dehydrogenase and phenylpyruvate decarboxylase completely failed to catabolize phenylalanine. The absence of these enzymes did not affect growth on tyrosine.Abbreviations RuMP ribulose monophosphate - EMS ethylmethanesulphonate - NTG N-methyl-N-nitro-N-nitrosoguanidine