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Holt Biology.pdf (Latest)



 


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PDFActivation of mitochondrial glutaminase promotes ceramide generation. Ceramide is a bioactive sphingolipid that has a well-established role in apoptosis. Although it is generated from sphingomyelin by the action of sphingomyelinase, the source of ceramide and the molecular mechanism of its generation remain poorly understood. In this study, we have evaluated the source and molecular mechanism of ceramide generation in response to inhibition of glutamine metabolism. Inhibition of glutaminase, which is the rate-limiting enzyme in glutamine metabolism, resulted in an increase in ceramide in both non-neuronal (B104) and neuronal (N18 and Neuro2A) cells. The increase in ceramide was dependent on activation of sphingomyelinase and ceramide synthase and the generation of sphingosine. It was also evident that the metabolic conversion of sphingosine to ceramide was essential, as observed by the failure of either ceramide synthase inhibition or the addition of exogenous sphingosine to prevent this increase in ceramide. However, we found that the generation of ceramide was not essential for the cytotoxic effect of inhibition of glutaminase as measured by lactate dehydrogenase release, suggesting that ceramide-induced apoptosis was being regulated at a site(s) other than the mitochondria.. F.R.H. designed and supervised the study. F.R.H., K.R., and R.F.L. performed the experiments. F.R.H., K.R., and M.J.K. analyzed the data. F.R.H. and K.R. wrote the manuscript with contributions from M.J.K. and R.F.L. Competing Interests {#FPar1} =================== F.R.H. and R.F.L. are authors on a patent, US 10131127 B2, related to this work. Scaling laws for recent human evolution In the past, when we came across a human species, we typically said something like, “They are less intelligent than us.” or “They are less intelligent than other humans.” I would guess that this is still fairly common in casual conversation. It is hard to find sources on the Internet that say humans are less intelligent than other humans. But it is still true

 

 

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Holt Biology.pdf (Latest)

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