Transporters – The View from Industry

The involvement of transport proteins in the disposition of drugs is receiving much attention of the scientific community. Recently, researchers from academia have surmised that drug transport rather than passive diffusion is the regular mechanism for molecules to cross cell membranes. On bare face value, however, sound evidence of the impact of transport proteins on clinical pharmacokinetics has been a trickle rather than a stream of convincing studies during the last decade, in stark contrast to the number of in vitro studies published. Progress in this area may have been impeded by a number of factors. Only a limited number of small‐molecule drugs fall within the physicochemical property space (i.e., high hydrophilicity and low passive permeability) that makes them predestined as transport protein substrates without other pharmacokinetic processes (e.g., passive diffusion, metabolism, nonspecific binding to tissue proteins) blurring the picture. The vast majority of drug molecules are lipophilic enough to be amenable to passive diffusion across cell membranes and to undergo metabolism to some extent. In these cases, clinical evidence relies heavily on the observation of pharmacokinetic drug–drug interactions not readily explained by the interference with drug metabolizing enzymes. Given the circumstances outlined above, it is not surprising that, based upon clinical observations, the final assessment as to the overall relevance of drug transport for clinical pharmacokinetics is still pending.     

The Biochemistry of Drug Metabolism – An Introduction

This review is part of a series of review articles on the metabolism of drugs and other xenobiotics published in Chemistry & Biodiversity. After a thorough discussion of metabolic reactions and their enzymes, this article focuses on genetically determined differences in drug and xenobiotic metabolism. After a short introduction on the causes for genetic differences, the first focus is on species differences in drug and xenobiotic metabolism. A major chapter is then dedicated to clinically relevant genetic polymorphisms in human drug metabolism and resultant ethnic differences. The last two chapters deal with sex‐dependent differences in drug metabolism and personalized pharmacotherapy related to inter‐individual differences in drug metabolism.     

Proterozoic photosynthesis – a critical review

Chlorophyll‐based photosynthesis has fuelled the biosphere since at least the early Archean, but it was the ecological takeover of oxygenic cyanobacteria in the early Palaeoproterozoic, and of photosynthetic eukaryotes in the late Neoproterozoic, that gave rise to a recognizably modern ocean–atmosphere system. The fossil record offers a unique view of photosynthesis in deep time, but is deeply compromised by differential preservation and non‐diagnostic morphologies. The pervasively polyphyletic expression of modern cyanobacterial phenotypes means that few Proterozoic fossils are likely to be members of extant clades; rather than billion‐year stasis, their similarity to modern counterparts is better interpreted as a combination of serial convergence and extinction, facilitated by high levels of horizontal gene transfer. There are few grounds for identifying cyanobacterial akinetes or crown‐group Nostocales in the Proterozoic record. Such recognition undermines the results of various ancestral state reconstruction analyses, as well as molecular clock estimates calibrated against demonstrably problematic Proterozoic fossils. Eukaryotic organisms are likely to have acquired their (stem‐group nostocalean) photoendosymbionts/plastids by at least the Palaeoproterozoic, but remained ecologically marginalized by incumbent cyanobacteria until the late Neoproterozoic appearance of suspension‐feeding animals.     

The Biochemistry of Drug Metabolism – An Introduction

This review continues a general presentation of the metabolism of drugs and other xenobiotics begun in three recent issues of Chemistry & Biodiversity. The present Part is dedicated to reactions of conjugation, namely methylation, sulfonation, and phosphorylation, glucuronidation and other glycosidations, acetylation and other acylations, the formation and fate of coenzyme A conjugates, glutathione conjugation, and the reaction of amines with carbonyl compounds. It presents the many transferases involved, their nomenclature, relevant biochemical properties, catalytic mechanisms, and the reactions they catalyze. Nonenzymatic reactions, mainly of glutathione conjugation, also receive due attention. A number of medicinally, environmentally, and toxicologically relevant examples are presented and discussed.     

Biofuels and invasive species from an African perspective – a review

A large number of proposed biofuel crops share the same traits as known invasive plant species, many of which are already present in Africa and include species such as Prosopis glandulosa Torrey (Mimosaceae), P. juliflora (Sw.) DC, Leucaena leucocephala (Lam.) de Wit (Mimosaceae), Azadirachta indica A. Juss. (Meliaceae), and others. In this paper, we mainly assess the impacts of invasive Prosopis species in Africa, particularly in Kenya and South Africa. Introduced Prosopis species have invaded over 4 million hectares in Africa, threatening crop and pasture production, reducing underground water reserves, and displacing native plant and animal species. This has major implications for millions of people who depend on natural resources for their survival. It is therefore suggested that known invasive or potentially invasive plant species not be introduced to countries or regions for biofuel production. If (after a stringent cost–benefit analysis) the introduction of a potentially invasive species is deemed critical for economic development and the benefits clearly outweigh the potential costs, countries should endeavour to abide by the Principles and Criteria for Sustainable Biofuel Production developed by the Roundtable on Sustainable Biofuels.     

Anaerobic digestion foaming causes – A review

Anaerobic digestion foaming has been encountered in several sewage treatment plants in the UK. Foaming has raised major concerns for the water companies due to significant impacts on process efficiency and operational costs. Several foaming causes have been identified over the past few years by researchers. However, the supporting experimental information is limited and in some cases absent. The present report aims to provide a detailed review of the current anaerobic digestion foaming problem and to identify gaps in knowledge regarding the theory of foam formation in anaerobic digesters.     

Unlike fellows – a review of primate–non‐primate associations

Throughout many regions of the tropics, non‐primate animals – mainly birds and mammals – have been observed to follow primate groups and to exploit dropped food and flushed prey. The anecdotal nature of most of the numerous reports on these primate–non‐primate associations (PNPAs) may obscure the biological significance of such associations. We review the existing literature and test predictions concerning the influence of primate traits (body size, activity patterns, dietary strategies, habitat, group size) on the occurrence of PNPAs. Furthermore, we examine the influence of non‐primates' dietary strategies on the occurrence of PNPAs, and the distribution of benefits and costs. We detected a strong signal in the geographic distribution of PNPAs, with a larger number of such associations in the Neotropics compared to Africa and Asia. Madagascar lacks PNPAs altogether. Primate body size, activity patterns, habitat and dietary strategies as well as non‐primate dietary strategies affect the occurrence of PNPAs, while primate group size did not play a role. Benefits are asymmetrically distributed and mainly accrue to non‐primates. They consist of foraging benefits through the consumption of dropped leaves and fruits and flushed prey, and anti‐predation benefits through eavesdropping on primate alarm calls and vigilance. Where quantitative information is available, it has been shown that benefits for non‐primates can be substantial. The majority of PNPAs can thus be categorized as cases of commensalism, while mutualism is very rare. Our review provides evidence that the ecological function of primates extends beyond their manifold interactions with plants, but may remain underestimated.