Cofactor (biochemistry)

Summary

A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that assist in biochemical transformations. The rates at which these happen are characterized in an area of study called enzyme kinetics. Cofactors typically differ from ligands in that they often derive their function by remaining bound. Cofactors can be classified into two types: inorganic ions and complex organic molecules called coenzymes. Coenzymes are mostly derived from vitamins and other organic essential nutrients in small amounts. (Some scientists limit the use of the term "cofactor" for inorganic substances; both types are included here.) Coenzymes are further divided into two types. The first is called a "prosthetic group", which consists of a coenzyme that is tightly (or even covalently) and permanently bound to a protein. The second ty

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This Master thesis comes within the framework of the PURR project (Partnership for Urban Resource Recovery), which is a collaboration between the Department of Water and Sanitation in Developing Countries (Sandec) at the Swiss Federal Institute of Aquatic Science and Technology (Eawag), the Institute of Environmental Science and Engineering (IESE) at the National University of Civil Engineering of Hanoi (HUCE), and the Laboratory for Environmental Biotechnology (LBE) at the Swiss Federal Institute of Technology Lausanne (EPFL). The PURR project is aiming to allow a comprehensive management of faecal sludge (FS) in Vietnamese urban areas. In that perspective, anaerobic co-digestion of FS with other type of organic waste is seen as a very promising technology. As the potential benefit from FS co-digestion is closely linked with the choice of co-substrates, this Master thesis was focusing on assessing the availability and suitability of potential co-substrates produced in the two case study cities Bac Ninh and Son La. By field research and interviews, a better understanding of the actual organic waste management was established. This showed that the actual organic waste management is not in favour of FS co-digestion as such. Indeed, all organic wastes separated at production source and therefore of high quality in terms of absence of impurities with disturbing effects, are already being reused, mainly as livestock feed. The remaining organic wastes are domestic waste, which cannot be used for anaerobic digestion (AD) process due to their high level of impurities related to their mixture with non-organic wastes. However, field research also revealed that rooms for improvements do exist for a better management of organic domestic waste. Nowadays they are most of the time dumped in landfills without any treatment. A segregation step would be really relevant to implement in order to decrease the related pollution and potential resource recovery of these valuable but underexploited wastes. Nevertheless, this would require political support from local authority in order to be efficient. Based on the organic waste assessment, co-treatment scenarios and related pros and constraints for FS co-digestion when considering the local context were developed. The use of segregated organic domestic waste came out to be the most sustainable scenario but is largely compromised by actual policy. The use of unfresh fruits and vegetables from market can be considered as the best compromise between technical and contextual constraints and would require less effort to be effective. In both scenarios, local support is a key factor for their effectiveness. Based on the results of the current report, the following statement can be deduced: If local support is provided, anaerobic co-digestion would be a relevant process for FS treatment. Otherwise, other treatment processes should be investigated.

2014

International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors.

Johan Auwerx, Liliane Michalik, Walter Wahli

The three peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear hormone receptor superfamily. They share a high degree of structural homology with all members of the superfamily, particularly in the DNA-binding domain and ligand- and cofactor-binding domain. Many cellular and systemic roles have been attributed to these receptors, reaching far beyond the stimulation of peroxisome proliferation in rodents after which they were initially named. PPARs exhibit broad, isotype-specific tissue expression patterns. PPARalpha is expressed at high levels in organs with significant catabolism of fatty acids. PPARbeta/delta has the broadest expression pattern, and the levels of expression in certain tissues depend on the extent of cell proliferation and differentiation. PPARgamma is expressed as two isoforms, of which PPARgamma2 is found at high levels in the adipose tissues, whereas PPARgamma1 has a broader expression pattern. Transcriptional regulation by PPARs requires heterodimerization with the retinoid X receptor (RXR). When activated by a ligand, the dimer modulates transcription via binding to a specific DNA sequence element called a peroxisome proliferator response element (PPRE) in the promoter region of target genes. A wide variety of natural or synthetic compounds was identified as PPAR ligands. Among the synthetic ligands, the lipid-lowering drugs, fibrates, and the insulin sensitizers, thiazolidinediones, are PPARalpha and PPARgamma agonists, respectively, which underscores the important role of PPARs as therapeutic targets. Transcriptional control by PPAR/RXR heterodimers also requires interaction with coregulator complexes. Thus, selective action of PPARs in vivo results from the interplay at a given time point between expression levels of each of the three PPAR and RXR isotypes, affinity for a specific promoter PPRE, and ligand and cofactor availabilities.

2006

Understanding the metabolism of tetrachloroethene-respiring Dehalobacter restrictus

Aamani Rupakula Boyanapalli

Tetra- and trichloroethene (PCE, TCE) are organohalides polluting the environment as a result of inappropriate use, storage, and disposal by various industries. Anthropogenic pollution by organohalides is a major source of concern because of their undesirable effects on human health. Remediation of contaminated sites by the use of microorganisms is a promising approach, especially under anaerobic conditions. Dehalobacter restrictus represents the paradigmatic member of the genus Dehalobacter, which in recent years has proven to be a major player in the biodegradation of a growing number of organohalides, both in situ and in the laboratory. D. restrictus grows only through anaerobic respiration of PCE and TCE with hydrogen as electron donor by a process known as organohalide respiration (OHR). To this day, only a single reductive dehalogenase (PceA/RdhA), the key enzyme in the OHR process, has been characterized on genetic and biochemical levels. However, recent genome analysis of D. restrictus has revealed the presence of 25 rdhA genes. Chapter 2 of this thesis describes a functional genomics and proteomics approach on D. restrictus with a focus on the diversity, composition and expression of rdh gene clusters. Genome analysis also revealed a complete corrinoid biosynthetic pathway, WL pathway for CO2 fixation and hydrogenases. Some of these were identified in proteomic analysis along with main PceABCT, RdhA14 and a few RdhK. OHR bacteria (OHRB) have developed different strategies to satisfy their need of corrinoid (Cobalamin/Vitamin B12 derivatives), as it is an essential cofactor of RdhAs forming the basis for Chapter 3. Obligate OHRB such as Dehalococcoides spp. and D. restrictus cannot de novo synthesize corrinoid. However. genome analysis revealed that in contrast to Dehalococcoides mccartyi, the genome of D. restrictus surprisingly has the complete series of genes for biosynthesis of corrinoid, however a single non-functional gene could account for the corrinoid auxotrophy. Comparative genomics within Dehalobacter spp. revealed that one of the five operons associated with the biosynthesis of corrinoid is unique to D. restrictus, which encoded enzymes corrinoid- salvaging and transport proteins. Omics during corrinoid starvation highlighted the importance of operon-2 in corrinoid homeostasis in D. restrictus along with indicating its augmented corrinoid salvaging strategy. Chapter 4 finally analyses the diversity of RdhK proteins in D. restrictus belonging to the CRP-FNR family of transcriptional regulators. Earlier studies in Desulfitobacterium spp. have allowed the identification and characterization of a transcriptional regulator, CprK known to be involved in the regulation of cpr gene cluster involved in OHR. Moreover recent genome analysis in D. restrictus, revealed the presence of 25 cprK-like rdhK genes found to be located in the direct neighbourhood of the rdh gene clusters strongly suggesting they could be implicated in regulating OHR in D. restrictus. A combination of in silico, in vivo and in vitro analyses have been attempted to characterize the role of a few RdhK proteins and understand the tri-partite interaction of the RdhK with the putative organohalide along with the putative-DNA binding regions (dehaloboxes). However, further efforts are still needed to elucidate the network regulating the OHR metabolism in D. restrictus.

EPFL2015

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