User talk:UniPharm/temp1

Desaturation Mechanism
Reaction: Stearoyl-CoA + AH 2 + O 2 = Oleoyl-CoA + A + 2 H 2 O

Known metabolic disfunctions
Some proliferators of Peroxisome are speculated to induce activity of stearoyl-CoA desaturase(EC 1.14.99.5) in the liver. Some have analyzed the changes in the stearoyl-CoA desaturase 1 complex (SCD1) mRNA to determine the reaction mechanism of the induction by stearoyl-CoA desaturase to peroxisome proliferators. SCD1 mRNA was analyzed from the livers of BALB/c mice that had been fed diets supplemented with clofibrate or gemfibrozil. Clofibrate was found to induce liver SCD1 mRNA levels 3-fold within 6 hr to a maximum of 22-fold in 30 hr. Gemfibrozil administration resulted in a similar induction pattern. This induction is primarily due to an increase in transcription of the SCD1 gene, as shown by nuclear run-on transcription assays and DNA deletion analysis of transfected SCD1-chloramphenicol acetyltransferase fusion genes. The cis-linked response element for peroxisome proliferator-activated receptor (PPAR) was localized to an AGGTCA consensus sequence between base pairs 664 to 642 of the SCD1 promoter. Clofibrate-mediated induction of SCD1 mRNA was shown to be independent of polyunsaturated fatty acids, with peroxisome proliferators and arachidonic acid having opposite effects on SCD1 mRNA levels. Additionally, the activation of SCD1 mRNA by clofibrate was inhibited 77% by cycloheximide administration. Levels of liver -actin and albumin mRNAs were unchanged by these dietary manipulations. Our data show that hepatic SCD1 gene expression is regulated by PPARs and suggest that peroxisome proliferators and polyunsaturated fatty acids act through distinct mechanisms.

Stearoyl-CoA desaturase 1 deficiency
Shown previously that mice with a targeted disruption in the gene for stearoyl-CoA desaturase 1 has increased sensitivity to insulin compared with a control, in some cases mice. Here we show that the gene in mice has increased the amount of signaling by insulin in muscle tissue. Thgat the basal tyrosine phosphorylation of a receptor of insulin and the substratesof the receptor of insulin 1 and 2 are elevated. The tyrosine phosphorylation of insulin-like growth factor-1 receptor was similar between two genes mice. The association of insulin receptor substrates 1 and 2 with p85 subunit of phosphatidylinositol 3-kinase as well as the phosphorylation of Akt-Ser-473 and Akt-Thr-308 are also elevated in the SCD1-/- mice. Interestingly, the mRNA levels, protein mass, and activity of the protein-tyrosine phosphatase-1B implicated in the attenuation of the insulin signal are reduced in the SCD1-/- mice, whereas the levels of the leukocyte antigen-related protein phosphatase are similar between two groups of mice. The content of glucose transporter 4 in the plasma membrane and basal as well as insulin-mediated glucose uptake are increased in the SCD1-/- mice. In addition, the muscle glycogen content and the activities of glycogen synthase and phosphorylase are increased in the SCD1-/- mice. We hypothesize that loss of SCD1 function induces increased insulin signaling at least in part by a reduction in the expression of protein-tyrosine phosphatase 1B. SCD1 could be a therapeutic target in the treatment of diabetes