A mouse model with compromised mitochondrial fatty acid synthesis has been engineered in order to assess the role of this pathway in mitochondrial function and overall health. Reduction in the expression of mitochondrial malonyl CoA-acyl carrier protein transacylase, a key enzyme in the pathway encoded by the nuclear Mcat gene, was achieved to varying extents in all examined tissues employing tamoxifen-inducible Cre-lox technology. Although affected mice consumed more food than control animals, they failed to gain weight, were less physically active, suffered from loss of white adipose tissue, reduced muscle strength, kyphosis, alopecia, hypothermia and shortened lifespan. The Mcat-deficient phenotype is attributed primarily to reduced synthesis, in several tissues, of the octanoyl precursors required for the posttranslational lipoylation of pyruvate and α-ketoglutarate dehydrogenase complexes, resulting in diminished capacity of the citric acid cycle and disruption of energy metabolism. The presence of an alternative lipoylation pathway that utilizes exogenous free lipoate appears restricted to liver and alone is insufficient for preservation of normal energy metabolism. Thus, de novo synthesis of precursors for the protein lipoylation pathway plays a vital role in maintenance of mitochondrial function and overall vigor.
1. Methyl-O-fl-D-fructofuranoside has been prepared by the action of yeast invertase on sucrose in the presence of methanol. 2. The fructoside has been used as a substrate for a mould-enzyme preparation (Taka-diastase). An examination of the products showed that both hydrolysis and transfructosylation occurred. 3. Sucrose could not be detected among the products of action upon mixtures of methyl ,Bfructoside and glucose, either by chromatographic fractionation or by the use of 14C-labelled glucose. 4. Taka-diastase acting on mixtures of raffinose and glucose formed sucrose. The incorporation of radioactive glucose into the molecule demonstrated that sucrose formation was the result of fructose transfer and not of melibiase (cx-galactosidase) action. 5. The implications of these findings are discussed in relation to the hypothesis that invertases form fructosyl-enzyme compounds as common intermediates in hydrolysis and transfructosylation.
When an aqueous solution of the fibroin of Bombyx mori is treated with chymotrypsin, a white precipitate is formed that contains approximately 60 % of the nitrogen of the original fibroin, and the remaining 40 % of the nitrogen remains in solution in the form of a mixture of water-soluble peptides. These two fractions, the precipitate and the mixture of soluble peptides, we propose to call fraction Cp and fraction Cs respectively, and these terms replace our earlier nomenclature CTP and CTL, which is no longer acceptable because the former has become the standard abbreviation for cytidine triphosphate. The new system has the advantage that it is applicable by analogy to the fractionation of fibroin by other enzymes: tryptic hydrolysis thus gives rise to fractions Tp and Ts, peptic hydrolysis to fEractions Pp and Ps. The precipitate, fraction Cp, is composed almost entirely of glycine, alanine, and serine, has a molecular weight of about 4000, and has a sequence that can be represented by
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