The complement system

In summary, the complement system represents a remarkably complex system of interacting proteins noteworthy for several features:

• 1.(1) The assembly and activation of complex proteolytic enzymes, each composed of more than one protein, which act sequentially on specific substrates.
• 2.(2) The biological activity of these enzymes requires the transfer of proteins from the fluid phase to the surface of target cells. This is possible, at least in part, by the ability of C3b and C4b to bind covalently to such surfaces.
• 3.(3) The system is extremely efficient; each of the proteolytically generated fragments appears to perform an important physiological function.
• 4.(4) The final event is the assembly of a macromolecular structure able to penetrate the cell membrane and in so doing lyse the cell.

     

The melanocortin system

The melanocortin system consists of melanocortin peptides derived from the proopiomelanocortin gene, five melanocortin receptors, two endogenous antagonists, and two ancillary proteins. This review provides an abbreviated account of the basic biochemistry, pharmacology, and physiology of the melanocortin system and highlights progress made in four areas. In particular, recent pharmacological and genetic studies have affirmed the role of melanocortins in pigmentation, inflammation, energy homeostasis, and sexual function. Development of selective agonists and antagonists is expected to further facilitate the investigation of these complex physiological functions and provide an experimental basis for new pharmacotherapies.     

The complement system

The complement system consists of a tightly regulated network of proteins that play an important role in host defense and inflammation. Complement activation results in opsonization of pathogens and their removal by phagocytes, as well as cell lysis. Inappropriate complement activation and complement deficiencies are the underlying cause of the pathophysiology of many diseases such as systemic lupus erythematosus and asthma. This review represents an overview of the complement system in an effort to understand the beneficial as well as harmful roles it plays during inflammatory responses.     

The Sec system

Proteins designated to be secreted by Escherichia coli are synthesized with an amino-terminal signal peptide and associate as nascent chains with the export-specific chaperone SecB. Translocation occurs at a multisubunit membrane-bound enzyme termed translocase, which consists of a peripheral preprotein-binding site and an ATPase domain termed SecA, a core heterotrimeric integral membrane protein complex with SecY, SecE and SecG as subunits, and an accessory integral membrane protein complex containing SecD and SecF. Major new insights have been gained into the cascade of preprotein targeting events and the enzymatic mechanism or preprotein translocation. It has become clear that preproteins are translocated in a stepwise fashion involving large nucleotide-induced conformational changes of the molecular motor SecA that propels the translocation reaction.     

The SOS system

In the bacterium Escherichia coli DNA damaging treatments such as ultraviolet or ionizing radiation induce a set of functions called collectively the SOS response, reviewed here. The regulation of the SOS response involves a repressor, the LexA protein, and an inducer, the RecA protein. After DNA damage an effector molecule is produced--possibly single stranded DNA--which activates the RecA protein to a form capable of catalysing proteolytic cleavage of LexA. The repressors of certain temperate prophages are cleaved under the same conditions, resulting in lysogenic induction. SOS functions are involved in DNA repair and mutagenesis, in cell division inhibition, in recovery of normal physiological conditions after the DNA damage is repaired, and possibly in cell death when DNA damage is too extensive. The SOS response also includes several chromosomal genes of unknown function, a number of plasmid encoded genes (bacteriocins, mutagenesis), and lysogenic induction of certain prophages. DNA damaging treatments seem to induce DNA repair and mutagenic activities and proviral development in many species, including mammalian cells. In general, substances which are genotoxic to higher eukaryotes induce the SOS response in bacteria. This correlation is the basis of the numerous bacterial tests for genotoxicity and carcinogenicity.     

The ubiquitin-proteasome system

The 2004 Nobel Prize in chemistry for the discovery of protein ubiquitination has led to the recognition of cellular proteolysis as a central area of research in biology. Eukaryotic proteins targeted for degradation by this pathway are first ‘tagged’ by multimers of a protein known as ubiquitin and are later proteolyzed by a giant enzyme known as the proteasome. This article recounts the key observations that led to the discovery of ubiquitin-proteasome system (UPS). In addition, different aspects of proteasome biology are highlighted. Finally, some key roles of the UPS in different areas of biology and the use of inhibitors of this pathway as possible drug targets are discussed.     

消化系统中的门脉系统

本文介绍了消化系统中的肝门脉系统、胆固门脉系统、小肠绒毛门脉系统系统、胰岛一外分泌门脉系统和唾液腺门脉系统的结构和功能。     

The system architecture of the BioPath system

BioPath is a prototype system for the interactive exploration of biochemical pathways. It has been developed as an electronic version of the famous Boehringer Biochemical Pathways map and offers various ways to access information on substances and pathways and to navigate through pathways. This paper describes the main features and the software architecture of BioPath. The companion paper [11] focuses on the advanced visualization incorporated into BioPath.     

The system is broken

When a scientist doing work in genomics, or cell biology, or biochemistry, or immunology submits a grant proposal to the US National Institutes of Health (NIH), the largest supporter of life science research in the world, his or her chance of it being funded are at historic lows.     

The multifaceted mismatch-repair system

By removing biosynthetic errors from newly synthesized DNA, mismatch repair (MMR) improves the fidelity of DNA replication by several orders of magnitude. Loss of MMR brings about a mutator phenotype, which causes a predisposition to cancer. But MMR status also affects meiotic and mitotic recombination, DNA-damage signalling, apoptosis and cell-type-specific processes such as class-switch recombination, somatic hypermutation and triplet-repeat expansion. This article reviews our current understanding of this multifaceted DNA-repair system in human cells.     

The gastrointestinal endocrine system

Gastrointestinal endocrinology is the study of the hormonal regulation of digestion. A number of characterized polypeptide hormones have been localized in specific gastroenteropancreatic endocrine cells. The fact that some of these hormones are also found in nerve and brain cells has given rise to the concept of a gut-brain axis. The functional capacities of these endocrine cells are determined by their anatomic location; the luminal exposure of gastroenteric endocrine cells represents an additional avenue for stimulation and release that is not open to pancreatic endocrine cells. Gastroenteropancreatic hormones regulate carbohydrate metabolism, gastric acid secretion, pancreatic exocrine and gallbladder function, gastrointestinal motility and blood flow. These important regulatory hormones may in turn be controlled by a series of gastroduodenal releasing hormones.Diabetes mellitus is the most important metabolic disorder related to a gastroenteropancreatic hormone imbalance. Most tumours producing these hormones are of pancreatic origin and produce a number of hormones; insulinomas and gastrinomas are detected readily because of the serious metabolic distrubances they cause. Other instances of altered circulating concentrations of these hormones result from rather than cause the disease.The challenge of future study is to determine if postprandial changes in the plasma concentrations of these hormones are sufficient or necessary, or both, for the control of digestion.     

The caudal neurosecretory system

Summary Recent information on the caudal neurosecretory system (urophysis) is collated, with special reference to cellular biology including neural relations, activity and chemistry of the biological principles associated with the urophysis, pharmacological analysis of the receptors for these principles, and their possible functions in a physiological sense. The existence of at least two principles, urotensins I and II, is well established. They differ pharmacologically and chemically and may arise from different cell types. At present, osmoregulation, cardiovascular regulation and reproduction are the most likely aspects of organismal physiology wherein these principles may be involved.Dedicated to Professor Doctor Berta Scharrer on the occasion of her seventieth birthday, with profound admiration and affection