Yeast sphingolipids: metabolism and biology

Sphingolipids have recently emerged as important bioactive molecules in addition to being critical structural components of cellular membranes. These molecules have been implicated in regulating cell growth, differentiation, angiogenesis, apoptosis, and senescene. To study sphingolipid mediated biology, it is necessary to investigate sphingolipid metabolism and its regulation. The yeast Saccharomyces cerevisiae has allowed such studies to take place as the sphingolipid metabolic and regulatory pathways appear conserved across species. Using yeast genetic approaches most enzymes of sphingolipid metabolism have been identified and cloned which has led to identification of their mammalian homologues. Many of the yeast enzymes are targets of fungal toxins thus underscoring the importance of this pathway in yeast cell regulation. This review focuses on the yeast sphingolipid metabolic pathway and its role in regulation of yeast biology. Implication of the insights gained from yeast to mammalian cell regulation are discussed.     

Ecosystems biology of microbial metabolism

The metabolic capabilities of many environmentally and medically important microbes can be quantitatively explored using systems biology approaches to metabolic networks. Yet, as we learn more about the complex microbe-microbe and microbe-environment interactions in microbial communities, it is important to understand whether and how system-level approaches can be extended to the ecosystem level. Here we summarize recent work that addresses these challenges at multiple scales, starting from two-species natural and synthetic ecology models, up to biosphere-level approaches. Among the many fascinating open challenges in this field is whether the integration of high throughput sequencing methods and mathematical models will help us capture emerging principles of ecosystem-level metabolic organization and evolution.     

Molecular biology of acetyl-CoA metabolism

We have characterized the expression of potential acetyl-CoA-generating genes (acetyl-CoA synthetase, pyruvate decarboxylase, acetaldehyde dehydrogenase, plastidic pyruvate dehydrogenase complex and ATP-citrate lyase), and compared these with the expression of acetyl-CoA-metabolizing genes (heteromeric and homomeric acetyl-CoA carboxylase). These comparisons have led to the development of testable hypotheses as to how distinct pools of acetyl-CoA are generated and metabolized. These hypotheses are being tested by combined biochemical, genetic and molecular biological experiments, which is providing insights into how acetyl-CoA metabolism is regulated.     

Postburn trauma insulin resistance and fat metabolism

Hyperglycemia and insulin resistance have long been recognized in severe burn patients. More recently, it has been observed that controlling hyperglycemia, or alleviating insulin resistance, is associated with improved outcomes. This has led to a renewed interest in the etiology of insulin resistance in this population. The postinjury hyperglycemic response appears to be associated with multiple metabolic abnormalities, such as elevated basal energy expenditure, increased protein catabolism, and, notably, significant alterations in fat metabolism. The synergy of all of the responses is not understood, although many studies have been conducted. In this article we will review the present understanding of the relationship between fat metabolism and insulin resistance posttrauma, and discuss some of the recent discoveries and potential therapeutic measures. We propose that the insulin resistance is likely related to the development of "ectopic" fat stores, i.e., triglyceride (TG) storage in sites such as the liver and muscle cells. Deposition of TG in ectopic sites is due to an increase in free fatty acid delivery secondary to catecholamine-induced lipolysis, in conjunction with decreased beta-oxidation within muscle and decreased hepatic secretion of fats. The resultant increases in intracellular TG or related lipid products may in turn contribute to alterations in insulin signaling.     

Oxidants, metabolism, and stem cell biology

Adult stem cells persist throughout the lifetime of the organism and may therefore require specific mechanisms to limit the effects of chronic oxidative stress. Recently, several instructive genetic mouse models have demonstrated the unique susceptibility of stem cells to perturbations in metabolic or redox homeostasis. These results have implications not only for stem cell biology but also suggest a mechanistic link between intracellular oxidants and the decline in regenerative function that occurs as a normal consequence of aging.     

Polyamines: metabolism to systems biology and beyond

Summary. Polyamines and the metabolic and physiopathological processes in which they are involved represent an active field of research that has been continuously growing since the seventies. In the last years, the trends in the focused areas of interest within this field since the 1970s have been confirmed. The impact of “-omics” in polyamine research remains too low in comparison with its deep impact on other biological research areas. These high-throughput approaches, along with systems biology and, in general, more systemic and holistic approaches should contribute to a renewal of this research area in the near future.