In eukaryotes, folate metabolism is compartmentalized between the cytoplasm and organelles. The folate pathways of mitochondria are adapted to serve the metabolism of the organism. In yeast, mitochondria support cytoplasmic purine synthesis through the generation of formate. This pathway is important but not essential for survival, consistent with the flexibility of yeast metabolism. In plants, the mitochondrial pathways support photorespiration by generating serine from glycine. This pathway is essential under photosynthetic conditions and the enzyme expression varies (...) with photosynthetic activity. In mammals, the expression of the mitochondrial enzymes varies in tissues and during development. In embryos, mitochondria supply formate and glycine for purine synthesis, a process essential for survival; in adult tissues, flux through mitochondria can favor serine production. The differences in the folate pathways of mitochondria depending on species, tissues and developmental stages, profoundly alter the nature of their metabolic contribution. BioEssays 28: 595–605, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

A marked feature of eukaryotic programmed cell death is an early drop in mitochondrial transmembrane potential. This results from the opening of permeability transition pores, which are composed of adenine nucleotide translocators and mitochondrial porins. The latter share striking similarites with bacterial porins, (including down‐regulation of their pore size by purine nucleotides), suggesting a common origin. The porins of some invasive bacteria play a crucial role during their accommodation inside the host cell and this co‐existence resembles the endosymbiotic origin (...) of mitochondria. The above observations suggest that early in eukaryotic evolution, former invaders may have used porin‐type channels to enter their host and to induce its death when the levels of its cytoplasmic purine nucleotides were dropped. The appearance of adenosine nucleotide translocators in the primitive eukaryotes, which permitted usage of the oxidative metabolism of the invaders, provided the basis for the permeability transition phenomena, now linked to the apoptotic process. Bcl‐2‐type molecules, being able to modulate the permeability transition pores by interaction with adenosine nucleotide translocators, may have played an essential role in conferring a means of controlling apoptosis. (shrink)

Although the type‐I interferon (IFN‐I) response is considered vertebrate‐specific, recent findings about the Intracellular Pathogen Response (IPR) in nematode Caenorhabditis elegans indicate that there are similarities between these two transcriptional immunological programs. The IPR is induced during infection with natural intracellular fungal and viral pathogens of the intestine and promotes resistance against these pathogens. Similarly, the IFN‐I response is induced by viruses and other intracellular pathogens and promotes resistance against infection. Whether the IPR and the IFN‐I response evolved in a (...) divergent or convergent manner is an unanswered and exciting question, which could be addressed by further studies of immunity against intracellular pathogens in C. elegans and other simple host organisms. Here we highlight similar roles played by RIG‐I‐like receptors, purine metabolism enzymes, proteotoxic stressors, and transcription factors to induce the IPR and IFN‐I response, as well as the similar consequences of these defense programs on organismal development. (shrink)

The emerging field of synthetic biology aims to engineer novel biological entities. The envisioned future bio-based economy builds largely on “cell factories”: organisms that have been metabolically engineered to sustainably produce substances for human ends. In this paper, we argue that synthetic biology’s goal of creating efficient production vessels for industrial applications implies a set of ontological assumptions according to which living organisms are machines. Traditionally, a machine is understood as a technological, isolated and controllable production unit consisting of parts. (...) But modified organisms, or hybrids, require us to think beyond the machine paradigm and its associated dichotomies between artificial and natural, organisms and artefacts. We ask: How may we conceptualise hybrids beyond limiting ontological categories? Our main claim is that the hybrids created by synthetic biology should be considered not as machines but as metabolic systems. We shall show how the philosophical account of metabolism can inform an ontology of hybrids that moves beyond what we call the “machine ontology”, considering that metabolism enables thinking beyond the dominant dichotomies and allows us to understand and design lifeforms in a bio-based economy. Thus, the aim of this paper is twofold: first, to develop the philosophical ontology of hybrids, and second, to move synthetic biology beyond the problematically limiting view of hybrids. (shrink)

Metabolism is a criterion of life. Three senses are distinguished. The weakest allows strong A-Life: virtual creatures having physical existence in computer electronics, but not bodies, are classes as 'alive'. The second excludes strong A-Life but allows that some non-biochemical A-Life robots could be classed as alive. The third, which stresses the body's self-production by energy budgeting and self-equilibrating energy exchanges of some (necessary) complexity, excludes both strong A-Life and living non-biochemical robots.

Reproduction places severe demands on the energy metabolism in human females. When physical work entails higher energy expenditure, not enough energy will be left for the support of the reproductive processes and temporal suppression of the reproductive function is expected. While energy needed for reproduction may be obtained by increases in energy intake, utilization of fat reserves, or reallocation of energy from basal metabolism, several environmental or physiological constraints render such solutions unlikely. For human ancestors increases in energy (...) intake were limited by availability of food, by labor of food preparation and by metabolic ceilings to energy assimilation. Energy stored as fat may support only a fraction of the requirements for reproduction (especially lactation). Effects of intense physical activity on basal metabolism may also interfere with fat accumulation during pregnancy. Finally, the female physiology may experience demands on increasing the basal metabolism as a consequence of physical activity and, at the same time, on decreasing the basal metabolism, when energy to support the ongoing pregnancy or lactation is inadequate. The resulting metabolic dilemmas could constitute a plausible cause for the occurrence of reproductive suppression in response to physical activity. It is, therefore, likely that allocating enough energy to the reproductive processes during periods when energy expenditure rises may be difficult due to physiological and bioenergetic constraints. Females attempting pregnancy in such conditions may compromise their lifetime reproductive output. A reproductive suppression occurring in low energy availability situations may thus represent an adaptive rather then a pathological response. (shrink)

Recent advances in research on iron metabolism have revealed the identity of a number of genes, signal transduction pathways, and proteins involved in iron regulation in mammals. The emerging paradigm is a coordination of homeostasis within a network of classical iron metabolic pathways and other cellular processes such as cell differentiation, growth, inflammation, immunity, and a host of physiologic and pathologic conditions. Iron, immunity, and infection are intricately linked and their regulation is fundamental to the survival of mammals. The (...) mutual dependence on iron by the host and invading pathogenic organisms elicits competition for the element during infection. While the host maintains mechanisms to utilize iron for its own metabolism exclusively, pathogenic organisms are armed with a myriad of strategies to circumvent these measures. This review explores iron metabolism in mammalian host, defense mechanisms against pathogenic microbes and the competitive devices of microbes for access to iron. (shrink)

Understanding terrestrial carbon metabolism is critical because terrestrial ecosystems play a major role in the global carbon cycle. Furthermore, humans have severely disrupted the carbon cycle in ways that will alter the climate system and directly affect terrestrial metabolism. Changes in terrestrial metabolism may well be as important an indicator of global change as the changing temperature signal. Improving our understanding of the carbon cycle at various spatial and temporal scales will require the integration of multiple, complementary (...) and independent methods that are used by different research communities. Tools such as air sampling networks, inverse numerical methods, and satellite data allow us to study the strength and location of the global- and continental-scale carbon sources and sinks. Bottom-up studies provide estimates of carbon fluxes at finer spatial scales and examine the mechanisms that control fluxes at the ecosystem, landscape, and regional scales. Bottom-up approaches include comparative and process studies that provide the necessary mechanistic information to develop and validate terrestrial biospheric models. An iteration and reiteration of top-down and bottom-up approaches will be necessary to help constrain measurements at various scales. We propose a major international effort to coordinate and lead research programs of global scope of the carbon cycle. (shrink)

I discuss the bearing on the mind-body problem of some general characteristics of living systems, including the physical basis of metabolism and the relation between living activity and cognitive capacities in simple organisms. I then attempt to describe stages in the history of animal life important to the evolution of subjective experience. Features of the biological basis of cognition are used to criticize arguments against materialism that draw on the conceivability of a separation between mental and physical. I also (...) argue against commonly held views about the "multiple realizability" of mental states of the kind seen in humans. The aim of the paper is to reconfigure and narrow the "explanatory gap" between mental and physical. (shrink)

Bone‐marrow mesenchymal stem cell (BM‐MSC) proliferation and lineage commitment are under the coordinated control of metabolism and epigenetics; the MSC niche contains low oxygen, which is an important determinant of the cellular metabolic state. In turn, metabolism drives stem cell fate decisions via alterations of the chromatin landscape. Due to the fundamental role of BM‐MSCs in the development of adipose tissue, bones and cartilage, age‐associated changes in metabolism and the epigenome perturb the balance between stem cell proliferation (...) and differentiation leading to stem cell depletion, fat accumulation and bone‐quality related diseases. Therefore, understanding the dynamics of the metabolism‐chromatin interplay is crucial for maintaining the stem cell pool and delaying the development and progression of ageing. This review summarizes the current knowledge on the role of metabolism in stem cell identity and highlights the impact of the metabolic inputs on the epigenome, with regards to stemness and pluripotency. (shrink)

The systems view on life and its emergence from complex chemistry has remarkably increased the scientific attention on metabolism in the last two decades. However, during this time there has not been much theoretical discussion on what constitutes a metabolism and what role it actually played in biogenesis. A critical and updated review on the topic is here offered, including some references to classical models from last century, but focusing more on current and future research. Metabolism is (...) considered as intrinsically related to the living but not necessarily equivalent to it. More precisely, the idea of “minimal metabolism”, in contrast to previous, top‐down conceptions, is formulated as a heuristic construct, halfway between chemistry and biology. Thus, rather than providing a complete or final characterization of metabolism, our aim is to encourage further investigations on it, particularly in the context of life's origin, for which some concrete methodological suggestions are provided. Also see the video abstract here:https://youtu.be/DP7VMKk2qpA. (shrink)

At Discorsi II.20, Machiavelli defines auxiliary arms as those, “whom a prince or a republic send captained and already paid for, for your aid.” My contention is that Machiavelli’s treatment of auxiliary arms is much more nuanced than it may seem at first glance. Throughout his works, Machiavelli articulates this type of force from the standpoint of the prince but also, surprisingly, from the standpoint of the people. In their princely employment, auxiliary arms act instrumentally as means for the projection (...) of power. However, analyzed from the standpoint of the people, auxiliary force exposes the projects of the state to the radically aleatory. Acknowledging the aspectival function played by the definition of auxiliaries in Machiavelli’s texts offers a new vantage point for re-reading Machiavelli on the nature of authority, power and the conflict of the umori. (shrink)

The pathway leading to the synthesis of purines for ATP, RNA, DNA and other cellular molecules involves the same enzymatic steps for all groups of organisms. However, the organization of the polypeptides catalyzing some of these steps differs strikingly from organism to organism.

The Fukushima catastrophe has led to important practical and conceptual shifts in contemporary Japanese architecture which in turn has led to a re-evaluation of the influential 1960s Japanese modern architecture movement, Metabolism. The Metabolists had the ambition to create a new Japanese society through techno-utopian city planning. The new generation of Japanese architects, after the Fukushima event, no longer seek evolutionally social change; rather, the disaster has made them re-consider what architecture is and what architects can do for people (...) who had everything snatched from them by technology and nature. Drawing on the architectural projects of Tange Kenzo and Metabolists in the 1960s and Ito Toyo’s ‘Home-for-All project’ in 2011, the paper explores this major paradigm shift in Japanese architectural theory and practices. (shrink)

The search for a systems‐level picture of metabolism as a web of molecular interactions provides a paradigmatic example of how the methods used to characterize a system can bias the interpretation of its functional meaning. Metabolic maps have been analyzed using novel techniques from network theory, revealing some non‐trivial, functionally relevant properties. These include a small‐world structure and hierarchical modularity. However, as discussed here, some of these properties might actually result from an inappropriate way of defining network interactions. Starting (...) from the so‐called bipartite organization of metabolism, where the two meaningful subsets (reactions and metabolites) are considered, most current works use only one of the subsets by means of so‐called graph projections. Unfortunately, projected graphs often ignore relevant biological and chemical constraints, thus leading to statistical artifacts. Some of these drawbacks and alternative approaches need to be properly addressed. (shrink)

In this paper, we aim at rethinking the concept of obesity in a way that better captures the connection between underlying medical aspects, on the one hand, and an individual’s developmental history, on the other. Our proposal rests on the idea that obesity is not to be understood as a phenotypic trait or character; rather, obesity represents one of the many possible states of a more complex phenotypic trait that we call ‘energy metabolism.’ We argue that this apparently simple (...) conceptual shift can help solve important theoretical misconceptions regarding the genetics, epigenetics, and development of obesity. In addition, we show that our proposal can be fruitfully paired with the concept of developmental channeling of a trait, which connects to the study of the plasticity and canalization of complex traits. Finally, we discuss the potential impact of our approach on the assessment, treatment, and social narratives of obesity. (shrink)

We recently examined gene expression during Xenopus tadpole tail appendage regeneration and found that carbohydrate regulatory genes were dramatically altered during the regeneration process. In this essay, we speculate that these changes in gene expression play an essential role during regeneration by stimulating the anabolic pathways required for the reconstruction of a new appendage. We hypothesize that during regeneration, cells use leptin, slc2a3, proinsulin, g6pd, hif1α expression, receptor tyrosine kinase (RTK) signaling, and the production of reactive oxygen species (ROS) to (...) promote glucose entry into glycolysis and the pentose phosphate pathway (PPP), thus stimulating macromolecular biosynthesis. We suggest that this metabolic shift is integral to the appendage regeneration program and that the Xenopus model is a powerful experimental system to further explore this phenomenon.Also watch the Video Abstract. (shrink)

Intermediary metabolism molecules are orchestrated into logical pathways stemming from history (L-amino acids, D-sugars) and dynamic constraints (hydrolysis of pyrophosphate or amide groups is the driving force of anabolism). Beside essential metabolites, numerous variants derive from programmed or accidental changes. Broken down, variants enter standard pathways, producing further variants. Macromolecule modification alters enzyme reactions specificity. Metabolism conform thermodynamic laws, precluding strict accuracy. Hence, for each regular pathway, a wealth of variants inputs and produces metabolites that are similar to (...) but not the exact replicas of core metabolites. As corollary, a shadow, paralogous metabolism, is associated to standard metabolism. We focus on a logic of paralogous metabolism based on diversion of the core metabolic mimics into pathways where they are modified to minimize their input in the core pathways where they create havoc. We propose that a significant proportion of paralogues of well-characterized enzymes have evolved as the natural way to cope with paralogous metabolites. A second type of denouement uses a process where protecting/deprotecting unwanted metabolites - conceptually similar to the procedure used in the laboratory of an organic chemist - is used to enter a completely new catabolic pathway. (shrink)

The point of departure of this article is the trend towards hybridisation in new technology development, which makes classical dichotomies between machines, human life and the environment obsolete and leads to the post-human world we live in today. We critically reflect on the post-human concept of the hybrid world. Although we agree with post-humanists that human life can no longer be opposed to machines but appears as a decentralized human-technology relation, alliance or network that constitutes a hybrid world, we ask (...) for a limit to hybridisation. After rejecting the concept of metabolism as such a limit, we explore the concept of the responsive conativity of material entities. The principle of conativity of material entities provides a materialist perspective on metabolism, which enables us to conceive material entities as self-assertive material entities that are differentiated from the environment. The principle of responsivity of material entities provides a materialist perspective on the post-human world in which material entities are responsive to each other and form alliances and networks. We propose to differentiate between the conativity and responsivity of material entities and propose the conativity of matter as a limit to hybridisation in the post-human world. (shrink)

When the existing order cannot offer a solution, the solution to climate crisis must come from the radical left, and this is precisely why Karl Marx’s idea of ecosocialism is more important than ever. In this context, it is worth revisiting not only the legacy of István Mészáros’s theory of ‘social metabolism’ and that of his successors – who can be categorised as comprising the ‘metabolic rift school’, which includes John Bellamy Foster, Paul Burkett, and Brett Clark –, but (...) also Karl Marx’s own theory of metabolism. In order to highlight the contemporary importance of Marx’s theory of metabolism after its long suppression in the twentieth century, this paper aims at classifying the three different levels of Marx’s concept of ‘metabolic rift’, which also entails clarifying three different levels of ‘metabolic shift’ as the theoretical foundation for updating Marx’s theory of postcapitalism in the age of global ecological crisis. (shrink)

Specificities of enzymes involved in plant specialized metabolism, including flavonoid biosynthesis, are generally promiscuous. This enzyme promiscuity has served as an evolutionary basis for new enzyme functions and metabolic pathways in land plants adapting to environmental challenges. This phenomenon may lead, however, to inefficiency in specialized metabolism and adversely affect metabolite‐mediated plant survival. How plants manage enzyme promiscuity for efficient specialized metabolism is, thus, an open question. Recent studies of flavonoid biosynthesis addressing this issue have revealed a (...) conserved strategy, namely, a homolog of chalcone isomerase with no catalytic activity binds to chalcone synthase, a key flavonoid pathway enzyme, to narrow (or rectify) the enzyme's highly promiscuous product specificity. Reducing promiscuity via specific protein–protein interactions among metabolic enzymes and proteins may be a solution adopted by land plants to achieve efficient operation of specialized metabolism, while the intrinsic promiscuity of enzymes has likely been retained incidentally. (shrink)

Citrate, an organic trivalent anion, is a major substrate for generation of energy in most cells. It is produced in mitochondria and used either in the Krebs' cycle or released into cytoplasm through a specific mitochondrial carriers. Citrate can also be taken up from blood through different plasma membrane transporters. In the cytoplasm, citrate can be used ultimately for fatty acid synthesis, which is increased in cancer cells. Here, we review the ways in which citrate can be transported and discuss (...) the changes in transport and metabolism that occur in cancer cells. The primary focus is on the prostate gland, which is known to produce and release large amounts of citrate during its normal secretory function. The significant changes that occur in citrate‐related metabolism and transport in prostate cancer are the second focus. This review strives to relate these mechanisms to molecular biology on the one hand and to clinical applications on the other. (shrink)

The hypothalamus is a specialized area in the brain that integrates the control of energy homeostasis. More than 70 years ago, it was proposed that the central nervous system sensed circulating levels of metabolites such as glucose, lipids and amino acids and modified feeding according to the levels of those molecules. This led to the formulation of the Glucostatic, Lipostatic and Aminostatic Hypotheses. It has taken almost that much time to demonstrate that circulating long‐chain fatty acids act as signals of (...) nutrient surplus in the hypothalamus. Moreover, pharmacological and/or genetic inhibition of fatty acid synthase, AMP‐activated protein kinase and carnitine palmitoyltransferase 1 results in profound decrease in feeding and body weight in rodents. The molecular mechanism behind these actions depends on changes in the cellular pool of malonyl‐CoA and fatty acyl‐CoAs. Current evidence also suggests that this pathway may play a major role in the physiological regulation of feeding, by integrating hormonal and nutrient‐derived signals in the hypothalamus. Here, we summarize what is known about hypothalamic fatty acid metabolism and feeding control and provide future directions for research. Understanding these molecular mechanisms could provide new targets for the treatment of obesity and related disorders. BioEssays 29: 248–261, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The gut microbiota is an important component of the human body and its immune‐modulating and metabolic activities are critical to maintain good health. Gut microbes, however, are sensitive to changes in diet, exposure to antibiotics, or infections, all of which cause transient disruptions in the microbial composition, a phenomenon known as dysbiosis. It is now recognized that microbial dysbiosis is at the root of many gastrointestinal disorders. However, the mechanisms through which bacterial dysbiosis initiates disease are not fully understood. Microbially‐derived (...) metabolites and their role in disease have also attracted significant attention. Identification of cancer‐associated bacteria and understanding the contributions of microbial metabolism in health and disease are exciting but challenging areas that will allow defining microbial biomarkers for predicting gastrointestinal disorders. Understanding the complex interactions between gut microbiota, diet, host immune system and host genetics will be critical to developing more personalized therapies and approaches to treat disease. (shrink)

K L Kahlbaum published in 1874 the first recorded description of catatonia. Akinetic catatonia is now defined as a neuropsychiatric syndrome principally characterised by akinesia, mutism, stupor, and catalepsy. 1 Even if some advances have been made in the recognition of catatonia, in particular by the development of different rating scales, 1 the pathophysiology of this syndrome is not clearly established. A right handed 14 year old girl presented with akinetic catatonia during an episode of depression in the context of (...) a bipolar type I disorder. Her catatonic status was characterised by akinesia with brief episodic spontaneous stereotyped movements, mutism, no spontaneous oral intake, catalepsy, waxy flexibility, and stupor with brief occasional eye contacts. This corresponded to a total score of 19 on the Northoff Catatonia Scale.1 Electroencephalogram performed one day after onset of symptoms showed diffuse theta activity with sporadic diffuse delta activity. Cerebral magnetic resonance imaging was normal. Brain positron emission tomographies (PET) were obtained on a CTI-Siemens HR+ tomograph. A first PET (PET1) using (18F(- fluorodeoxyglucose (FDG) was performed on day 2 in a drug free state. Thereafter, intramuscular injection of 2 mg of lorazepam induced rapid clinical remission of the akinetic phase. Oral lorazepam was then given (3.75 mg/day) during five days. On day 8, a second PET with FDG was performed while the patient was treated by olanzapine (15 mg/day) and presented hyperactivity, logorrhoea, and disinhibition characterised by uncontrolled social interactions and physical contacts. Neuropsychological testing performed some days after remission revealed no apraxia or language disturbances but dysfunction of executive tasks manifested in the revised Wisconsin card sorting, the Tower of London, Stroop, and Trailmaking tests. Voxel based analyses comparing patient’s cerebral glucose metabolism with that of 29 right handed healthy controls (16 women and 13 men, mean age 32) were performed using Statistical Parametric Mapping (SPM99) (Wellcome Department of Cognitive Neurology, London, UK).. (shrink)

Over the past several years, discoveries from mouse genetics have had direct impact on our understanding of vitamin A metabolism. Although the metabolism of vitamin A in the mouse does have some special features (for example very large stores of liver and pulmonary retinyl esters), the ability to construct knockout and transgenic mouse models has yielded an impressive amount of information directly relevant to understanding the general principles of vitamin A transport, storage and degradation. We discuss below the (...) metabolism of vitamin A through a number of genetically engineered mouse strains with alterations in genes that affect this metabolism. The novelty of this experimental approach is evidenced by the fact that the oldest of these strains was first reported only eight years ago.1) BioEssays 23:409–419, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

In this article, we propose some fundamental requirements for the appearance of adaptivity. We argue that a basic metabolic organization, taken in its minimal sense, may provide the conceptual framework for naturalizing the origin of teleology and normative functionality as it appears in living systems. However, adaptivity also requires the emergence of a regulatory subsystem, which implies a certain form of dynamic decoupling within a globally integrated, autonomous system. Thus, we analyze several forms of minimal adaptivity, including the special case (...) of motility. We go on to explain how an open-ended complexity growth of motility-based adaptive agency, namely, behavior, requires the appearance of the nervous system. Finally, we discuss some implications of these ideas for embodied robotics. (shrink)

The point of departure of this article is the trend towards hybridisation in new technology development, which makes classical dichotomies between machines, human life and the environment obsolete and leads to the post-human world we live in today. We critically reflect on the post-human concept of the hybrid world. Although we agree with post-humanists that human life can no longer be opposed to machines but appears as a decentralized human-technology relation, alliance or network that constitutes a hybrid world, we ask (...) for a limit to hybridisation. After rejecting the concept of metabolism as such a limit, we explore the concept of the responsive conativity of material entities. The principle of conativity of material entities provides a materialist perspective on metabolism, which enables us to conceive material entities as self-assertive material entities that are differentiated from the environment. The principle of responsivity of material entities provides a materialist perspective on the post-human world in which material entities are responsive to each other and form alliances and networks. We propose to differentiate between the conativity and responsivity of material entities and propose the conativity of matter as a limit to hybridisation in the post-human world. (shrink)

The concentration of low‐density lipoprotein (LDL) cholesterol (C) in plasma is a key determinant of cardiovascular disease risk and human genetic studies have long endeavoured to elucidate the pathways that regulate LDL metabolism. Massive genome‐wide association studies (GWASs) of common genetic variation associated with LDL‐C in the population have implicated SORT1 in LDL metabolism. Using experimental paradigms and standards appropriate for understanding the mechanisms by which common variants alter phenotypic expression, three recent publications have presented divergent and even (...) contradictory findings. Interestingly, although these reports each linked SORT1 to LDL metabolism, they did not agree on a mechanism to explain the association. Here, we review recent mechanistic studies of SORT1 – the first gene identified by GWAS as a determinant of plasma LDL‐C to be evaluated mechanistically. (shrink)

In addition to its well‐known role as a coenzyme in oxidation–reduction reactions, the distinct role of NAD as a precursor for molecules involved in cell regulation has been clearly established. The involvement of NAD in these regulatory processes is based on its ability to function as a donor of ADP‐ribose; NAD synthesis is therefore required to avoid depletion of the intracellular pool. The rising interest in the biosynthetic routes leading to NAD formation and the highly conserved nature of the enzymes (...) involved prompted us to reconstruct the NAD biosynthetic routes operating in distinct eukaryotic organisms. The evidence obtained from biochemical and computational analysis provides a good example of how complex metabolic pathways may evolve. In particular, it is proposed that the development of several NAD biosynthetic routes during evolution has led to partial functional redundancy, allowing a given pathway to freely acquire novel functions unrelated to NAD biosynthesis. BioEssays 25:683–690, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Defects in man in four steps of 4‐aminobutyric acid (GABA) metabolism may interefere with the function of this major inhibitory neurotransmitter. Glutamic acid decarboxylase, 4‐aminobutyric acid aminotransferase, succinic semialdehyde dehydrogenase, and homocarnosinase are closely identified with the brain, but two of these enzymes are expressed in cultured peripheral cells, which may permit novel approaches to the study of the metabolism and regulation of GABA.

This article views capitalism not only as a mode of production, but also as a mediation of the reproduction of life, following the concept of ‘social metabolism’ that Marx employs to analyze the interaction between the individuals composing a society and their natural environment. Insofar as the ‘value-form’ is the distinctive social relation of capitalism, it appears necessary to ask whether the metabolic process of reproduction can be fully subsumed under this form. Marx takes for granted the idea that (...) the reproduction of labor-power consists only in the consumption of commodities resulting from abstract labor, thus omitting the appropriation of unpaid domestic work, mostly performed by women. Feminist criticism clarifies how capitalism always depends on some reproductive work being appropriated for the accumulation of surplus-value without being integrated in the value-form. Following Jason W. Moore, I attempt to indicate that the same logic is at work for the reproduction... (shrink)

We provide a mathematical study of a model of energy metabolism and hemodynamics of glioma allowing a better understanding of metabolic modifications leading to anaplastic transformation from low grade glioma.This mathematical analysis allows ultimately to unveil the solution to a viability problem which seems quite pertinent for applications to medecine.

The reprogramming of metabolism has been identified as one of the hallmarks of cancer. It is becoming more and more frequent to connect other diseases with metabolic reprogramming. This article aims to argue that metabolic reprogramming is not driven by disease but instead is the main hallmark of metabolism, based on its dynamic behavior that allows it to continuously adapt to changes in the internal and external conditions.