Enzymes of Sphingolipid metabolism in Drosophila melanogaster

Sphingolipids are important structural components of membranes that delimit the boundaries of cellular compartments, cells and organisms. They play an equally important role as second messengers, and transduce signals across or within the compartments they define to initiate physiological changes during development, differentiation and a host of other cellular events. For well over a century Drosophila melanogaster has served as a useful model organism to understand some of the fundamental tenets of development, differentiation and signaling in eukaryotic organisms. Directed approaches to study sphingolipid biology in Drosophila have been initiated only recently. Nevertheless, earlier phenotypic studies conducted on genes of unknown biochemical function have recently been recognized as mutants of enzymes of sphingolipid metabolism. Genome sequencing and annotation have aided the identification of homologs of recently discovered genes. Here we present an overview of studies on enzymes of the de novo sphingolipid biosynthetic pathway, known mutants and their phenotypic characterization in Drosophila.Received 14 June 2004; received after revision 15 August 2004; accepted 21 August 2004     

AMP-activated protein kinase in skeletal muscle: From structure and localization to its role as a master regulator of cellular metabolism

The AMP-activated protein kinase (AMPK) is a metabolite sensing serine/threonine kinase that has been termed the master regulator of cellular energy metabolism due to its numerous roles in the regulation of glucose, lipid, and protein metabolism. In this review, we first summarize the current literature on a number of important aspects of AMPK in skeletal muscle. These include the following: (1) the structural components of the three AMPK subunits (i.e. AMPKα, β, and γ), and their differential localization in response to stimulation in muscle; (2) the biochemical regulation of AMPK by AMP, protein phosphatases, and its three known upstream kinases, LKB1, Ca²⁺/calmodulin-dependent protein kinase kinase (CaMKK), and transforming growth factor-β-activated kinase 1 (TAK1); (3) the pharmacological agents that are currently available for the activation and inhibition of AMPK; (4) the physiological stimuli that activate AMPK in muscle; and (5) the metabolic processes that AMPK regulates in skeletal muscle. Received 04 May 2008; received after revision 14 June 2008; accepted 14 July 2008     

The role of the kidney in gastrin metabolism in the rat

Résumé Les taux moyens de sécrétion d'acide gastrique due à l'injection par voie i.v. du SHGI et de gastrine bovine brute ont été sensiblement plus élevées et les périodes de réaction plus longues chez les rats testés que chez les rats de contrôle. Aucune différences significative n'a été observée ni dans le taux moyen de sécrétion acide ni dans la période de réaction chez les deux types de rats, après injection d'histamine dihydrochloride.

---

---

The authors are grateful to M.R.C. London for the SHGI sent to M.O.O. The work has been made possible by a fund from the University of Ibadan Senate Research Grant given to M.O.O.     

Thiamine triphosphate metabolism and its turnover in the rat liver

Summary When rats were injected with a thiamine disulfide derivative, the content of thiamine triphosphate (TTP) in the liver doubled within 3 h after a preceeding rise in thiamine pyrophosphate; it then returned to the basal level within the next 3h, indicating a net increase of TTP in vivo and its rapid turnover.     

Control of adenine nucleotide metabolism and glycolysis in vertebrate skeletal muscle during exercise

The turnover of adenosine triphosphate (ATP) in vertebrate skeletal muscle can increase more than a hundredfold during high-intensity exercise while the content of ATP in muscle may remain virtually unchanged. This requires that the rates of ATP hydrolysis and ATP synthesis are exactly balanced despite large fluctuations in reaction rates. ATP is regenerated initially at the expense of phosphocreatine (PCr) and then mainly through glycolysis from muscle glycogen. The increased ATP turnover in contracting muscle will cause an increase in the contents of adenosine diphosphate (ADP), adenosine monophosphate (AMP) and inorganic phosphate (P_i), metabolites that are substrates and activators of regulatory enzymes such as glycogen phosphorylase and phosphofructokinase. An intracellular metabolic feedback mechanism is thus activated by muscle contraction. How muscle metabolism is integrated in the intact body under physiological conditions is not fully understood. Common frogs are suitable experimental animals for the study of this problem because they can readily be induced to change from rest to high-intensity exercise, in the form of swimming. The changes in metabolites and effectors in gastrocnemius muscle were followed during exercise, post-exercise recovery and repeated exercise. The results suggest that glycolytic flux in muscle is modulated by signals from outside the muscle and that fructose 2,6-bisphosphate is a key signal in this process.     

Lipids in the silk-glands ofBombyx mori and their probable role in secretory metabolism

Résumé Dans les glandes séricigènes des mues de la chenille duBombyx mori, les lipides sudanophiles s'accumulent progressivement jusqu'à la 5e mue et s'épuisent complètement pendant la formation du cocon. Une étude systématique des divers systèmes d'enzymes montre que les lipides fournissent par oxydation-réduction l'énergie nécessaire au métabolisme sécrétoire des cellules des glandes pendant les dernières mues.     

Insulin and its possible role in the artificial hibernation

Riassunto Gli autori hanno studiato la possibilità di facilitare l'ipotermia degli omeotermi mediante l'insulina. Hanno osservato che gli animali ibernati in ipoglicemia insulinica non presentano mai chok post-perfrigerazione, che il risveglio è sempre molto rapido e che l'ibernazione ha un decorso molto più soddisfacente dei controlli non trattati con insulina.     

Triacylglycerol hydrolase: role in intracellular lipid metabolism

Recent scientific advances have revealed the identity of several enzymes involved in the synthesis, storage and catabolism of intracellular neutral lipid storage droplets. An enzyme that hydrolyzes stored triacylglycerol (TG), triacylglycerol hydrolase (TGH), was purified from porcine, human and murine liver microsomes. In rodents, TGH is highly expressed in liver as well as heart, kidney, small intestine and adipose tissues, while in humans TGH is mainly expressed in the liver, adipose and small intestine. TGH localizes to the endoplasmic reticulum and lipid droplets. The TGH genes are located within a cluster of carboxylesterase genes on human and mouse chromosomes 16 and 8, respectively. TGH hydrolyzes stored TG, and in the liver, the lipolytic products are made available for VLDL-TG synthesis. Inhibition of TGH activity also inhibits TG and apolipoprotein B secretion by primary hepatocytes. A role for TGH in basal TG lipolysis in adipocytes has been proposed. TGH expression and activity is both developmentally and hormonally regulated. A model for the function of TGH is presented and discussed with respect to tissue specific functions.     

Matriptase and its putative role in cancer

Tumor progression and metastasis are the pathologic effects of uncontrolled or deregulated invasive growth, a process in which proteases play a fundamental role. They mediate the degradation of extracellular matrix components and intercellular cohesive structures to allow migration of the cells into the extracellular environment and activate growth and angiogenic factors. In addition to metalloproteases and the plasminogen activation system, another protease, matriptase, contributes substantially to these processes. Matriptase is a type II transmembrane trypsin-like serine protease that is expressed by cells of epithelial origin and is overexpressed in a variety of human cancers. It has been suggested that this protease not only facilitates cellular invasiveness but may also activate oncogenic pathways. This review summarizes current knowledge about matriptase, its putative role in tumor initiation and progression, and its potential as a novel target in anti-cancer therapy. Received 29 June 2006; received after revision 1 August 2006; accepted 19 September 2006     

Dimethyltryptamin: Its metabolism in man; the relation of its psychotic effect to the serotonin metabolism

Zusammenfassung Es wird festgestellt, dass Dimethyltryptamin — bei normalen Versuchspersonen — eine dem Meskalin und dem LSD-25 ähnliche psychotische Wirkung hat. Der durch Dimethyltryptamin induzierte Zustand beginnt schon 3–5 min nach Injektion und verschwindet bereits nach 1 h. Der Urin der Versuchspersonen wurde papier-chromatographisch und kolorimetrisch auf Indolverbindungen geprüft. 3-Indolylessigsäure wird als hauptsächlichstes Abbauprodukt des Dimethyltryptamins gefunden, wovon der grösste Teil in alkali-labiler Form gebunden ist. Die Menge der ausgeschiedenen 5-Hydroxy-indolylessigsäure ist nach dem Versuch wesentlich grösser als vorher. Die Stoffwechselzusammenhänge mit dem psychotischen Zustand werden diskutiert.     

Acridine orange action on the biochemical metabolism of the leaf tissues of the tobacco Plant

Zusammenfassung Blätter von Tabakpflanzen wurdenin vivo undin vitro mit 20 Acridinorange-Lösung behandelt und danach die Aktivitäten von Katalase, Polyphenoloxydase und Kohlensäureanhydrase bestimmt. Nach zwanzigtägigerIn-vivo-Behandlung machte sich eine Störung der Oxydationsprozesse bemerkbar. Ähnliche Befunde ergaben sich bei Pflanzen, welche das Bild einer Viruskrankheit zeigten und von einer Mutterpflanze stammten, deren Blütenknospen mit 2% Acridinorange-Lösung behandelt worden waren.     

The role of apolipoprotein E in lipid metabolism in the central nervous system

The critical roles of apolipoprotein E (apoE) in regulating plasma lipid and lipoprotein levels have been extensively studied for over 2 decades. However, an understanding of the roles of apoE in the central nervous system (CNS) is less certain. This review will summarize the available experimental results on the role of apoE in CNS lipid homeostasis with respect to its modulation of sulfatide trafficking, alteration of CNS cholesterol homeostasis and apoE-induced changes in phospholipid molecular species in specialized subcellular membrane fractions. The results indicate that apoE mediates sulfatide trafficking and metabolism in the CNS. Moreover, although apoE does not affect the cholesterol mass content or the phospholipid mass levels and composition in the CNS as a whole, apoE modulates cholesterol and phospholipid homeostasis in selective subcellular membrane compartments. Through elucidating the roles of apoE in CNS lipid metabolism, new insights into overall functions of apoE in neurobiology can be accrued ultimately, leading to an increased understanding of CNS lipid metabolism and the identification of novel therapeutic targets for CNS diseases.Received 9 January 2004; received after revision 28 February 2004; accepted 10 March 2004