IUBMB Life

Polyamines are ubiquitous small basic molecules that play multiple essential roles in mammalian physiology. Their cellular content is highly regulated and there is convincing evidence that altered metabolism is involvement in many disease states. Drugs altering polyamine levels may therefore have a variety of important targets. This review will summarize the current state of understanding of polyamine metabolism and function, the regulation of polyamine content, and heritable pathological conditions that may be derived from altered polyamine metabolism. © 2009 IUBMB IUBMB Life 61(9): 880–894, 2009

Các glycerophospholipid phosphatidylcholine (PC) và phosphatidylethanolamine (PE) chiếm hơn 50% tổng số loài phospholipid trong màng eukaryote và do đó đóng vai trò quan trọng trong cấu trúc và chức năng của các màng này. Trong hầu hết các tế bào eukaryote, PC và PE được tổng hợp thông qua phản ứng aminocoholphosphotransferase, sử dụng sn‐1,2‐diradylglycerol và CDP‐choline hoặc CDP‐ethanolamine, tương ứng. Đây là bước cuối cùng trong một con đường sinh tổng hợp được gọi là đường đi Kennedy, được đặt tên theo Eugene Kennedy, người đã làm sáng tỏ nó hơn 50 năm trước. Bài viết này sẽ đề cập đến nhiều khía cạnh của đường đi Kennedy bao gồm: từng bước trong quá trình sinh tổng hợp, các chức năng và vai trò của các sản phẩm phospholipid PC và PE, và cách mà đường đi Kennedy có khả năng trở thành một mục tiêu hóa trị liệu chống lại ung thư và các bệnh nhiễm trùng khác nhau. © 2010 IUBMB IUBMB Life, 62(6): 414–428, 2010

Monocarboxylate transporter (MCT) isoforms 1–4 catalyze the proton‐linked transport of monocarboxylates such as L‐lactate across the plasma membrane, whereas MCT8 and MCT10 are thyroid hormone and aromatic amino acid transporters, respectively. The importance of MCTs is becoming increasingly evident as their extensive physiological and pathological roles are revealed. MCTs 1–4 play essential metabolic roles in most tissues with their distinct properties, expression profile, and subcellular localization matching the particular metabolic needs of a tissue. Important metabolic roles include energy metabolism in the brain, skeletal muscle, heart, tumor cells, and T‐lymphocyte activation, gluconeogenesis in the liver and kidney, spermatogenesis, bowel metabolism of short‐chain fatty acids, and drug transport. MCT8 is essential for thyroid hormone transport across the blood–brain barrier. Genetic perturbation of MCT function may be involved in disease states such as pancreatic β‐cell malfunction (inappropriate MCT1 expression), chronic fatigue syndromes (impairment of muscle MCT function), and psychomotor retardation (MCT8 mutation). MCT expression can be regulated at both the transcriptional and post‐transcriptional levels. Of particular importance is the upregulation of muscle MCT1 expression in response to training and MCT4 expression in response to hypoxia. The latter is mediated by hypoxia inducible factor 1α and often observed in tumor cells that rely almost entirely on glycolysis for their energy provision. The recent discovery of potent and specific MCT1 inhibitors that prevent proliferation of T‐lymphocytes confirms that MCTs may be promising pharmacological targets including for cancer chemotherapy. © 2011 IUBMB IUBMB Life, 2011.

The long term use of many insecticides is continually threatened by the ability of insects to evolve resistance mechanisms that render the chemicals ineffective. Such resistance poses a serious threat to insect pest control both in the UK and worldwide. Resistance may result from either an increase in the ability of the insect to detoxify the insecticide or by changes in the target protein with which the insecticide interacts. DDT, the pyrethrins and the synthetic pyrethroids (the latter currently accounting for around 17% of the world insecticide market), act on the voltage‐gated sodium channel proteins found in insect nerve cell membranes. The correct functioning of these channels is essential for normal transmission of nerve impulses and this process is disrupted by binding of the insecticides, leading to paralysis and eventual death. Some insect pest populations have evolved modifications of the sodium channel protein which prevent the binding of the insecticide and result in the insect developing resistance. Here we review some of the work (done at Rothamsted Research and elsewhere) that has led to the identification of specific residues on the sodium channel that may constitute the DDT and pyrethroid binding sites. IUBMB Life, 59: 151‐162, 2007

Glucose‐6‐phosphate dehydrogenase (G6PD) is the rate‐limiting enzyme of the pentose phosphate pathway. Many scientists think that the roles and regulation of G6PD in physiology and pathophysiology have been well established as the enzyme was first identified 80 years ago. And that G6PD has been extensively studied especially with respect to G6PD deficiency and its association with hemolysis, and with respect to the role G6PD plays in lipid metabolism. But there has been a growing understanding of the central importance of G6PD to cellular physiology as it is a major source of NADPH that is required by many essential cellular systems including the antioxidant pathways, nitric oxide synthase, NADPH oxidase, cytochrome p450 system, and others. Indeed G6PD is essential for cell survival. It has also become evident that G6PD is highly regulated by many signals that affect transcription, post‐translation, intracellular location, and interactions with other protein. Pathophysiologic roles for G6PD have also been identified in such disease processes as diabetes, aldosterone‐induced endothelial dysfunction, cancer, and others. It is now clear that G6PD is under complex regulatory control and of central importance to many cellular processes. In this review the biochemistry, regulatory signals, physiologic roles, and pathophysiologic roles for G6PD that have been elucidated over the past 20 years are discussed. 2012 IUBMB IUBMB Life, 2012

The c‐Jun N‐terminal kinases (JNKs) were originally identified by their ability to phosphorylate c‐Jun in response to UV‐irradiation, but now are recognized as critical regulators of various aspects of mammalian physiology, including: cell proliferation, cell survival, cell death, DNA repair and metabolism. JNK‐mediated phosphorylation enhances the ability of c‐Jun, a component of the AP‐1 transcription factor, to activate transcription, in response to a plethora of extracellular stimuli. The JNK activation leads to induction of AP‐1‐dependent target genes involved in cell proliferation, cell death, inflammation, and DNA repair. The JNKs, which are encoded by three different Jnk loci, are now known to be regulated by many other stimuli, from pro‐inflammatory cytokines to obesity, in addition to UV‐irradiation. Targeted disruption of the Jnk loci in mice has proved to be a critical tool in better understanding their physiological functions. Such studies revealed that the JNKs play important roles in numerous cellular processes, including: programmed cell death, T cell differentiation, negative regulation of insulin signaling, control of fat deposition, and epithelial sheet migration. Importantly, the JNKs have become prime targets for drug development in several important clinical areas, including: inflammation, diabetes, and cancer. IUBMB Life, 57: 283‐295, 2005

The antibacterial activity of honey has been known since the 19th century. Recently, the potent activity of honey against antibiotic‐resistant bacteria has further increased the interest for application of honey, but incomplete knowledge of the antibacterial activity is a major obstacle for clinical applicability. The high sugar concentration, hydrogen peroxide, and the low pH are well‐known antibacterial factors in honey and more recently, methylglyoxal and the antimicrobial peptide bee defensin‐1 were identified as important antibacterial compounds in honey. The antibacterial activity of honey is highly complex due to the involvement of multiple compounds and due to the large variation in the concentrations of these compounds among honeys. The current review will elaborate on the antibacterial compounds in honey. We discuss the activity of the individual compounds, their contribution to the complex antibacterial activity of honey, a novel approach to identify additional honey antibacterial compounds, and the implications of the novel developments for standardization of honey for medical applications. © 2011 IUBMB IUBMB Life, 2011.s

Increasing evidence suggests a role for intracellular reactive oxygen species (ROS) as mediators of normal and pathological signal transduction pathways. In particular, a growing list of recent reports have demonstrated a rapid and significant increases in intracellular ROS following growth factor or cytokine stimulation. These ROS appear essential for a host of downstream signaling events. Biochemical characterization of this ligand‐activated ROS production has revealed important information regarding the molecular composition of the cellular oxidases and the regulation of their activity by small GTPases. Work is proceeding on identifying strategies to identify how ROS might specifically regulate signaling pathways by altering the activity of direct target molecules. This review will focus on the progress in the rapid emerging area of oxidant or redox‐dependent signal transduction and speculate how these insights might alter our view and treatment of diseases thought to be caused by oxidative stress.