Hasil untuk "Biochemistry"

Anna Stincone, A. Prigione, T. Cramer et al.

The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress. The PPP shares reactions with the Entner–Doudoroff pathway and Calvin cycle and divides into an oxidative and non‐oxidative branch. The oxidative branch is highly active in most eukaryotes and converts glucose 6‐phosphate into carbon dioxide, ribulose 5‐phosphate and NADPH. The latter function is critical to maintain redox balance under stress situations, when cells proliferate rapidly, in ageing, and for the ‘Warburg effect’ of cancer cells. The non‐oxidative branch instead is virtually ubiquitous, and metabolizes the glycolytic intermediates fructose 6‐phosphate and glyceraldehyde 3‐phosphate as well as sedoheptulose sugars, yielding ribose 5‐phosphate for the synthesis of nucleic acids and sugar phosphate precursors for the synthesis of amino acids. Whereas the oxidative PPP is considered unidirectional, the non‐oxidative branch can supply glycolysis with intermediates derived from ribose 5‐phosphate and vice versa, depending on the biochemical demand. These functions require dynamic regulation of the PPP pathway that is achieved through hierarchical interactions between transcriptome, proteome and metabolome. Consequently, the biochemistry and regulation of this pathway, while still unresolved in many cases, are archetypal for the dynamics of the metabolic network of the cell. In this comprehensive article we review seminal work that led to the discovery and description of the pathway that date back now for 80 years, and address recent results about genetic and metabolic mechanisms that regulate its activity. These biochemical principles are discussed in the context of PPP deficiencies causing metabolic disease and the role of this pathway in biotechnology, bacterial and parasite infections, neurons, stem cell potency and cancer metabolism.

R. Tsao

Polyphenols are the biggest group of phytochemicals, and many of them have been found in plant-based foods. Polyphenol-rich diets have been linked to many health benefits. This paper is intended to review the chemistry and biochemistry of polyphenols as related to classification, extraction, separation and analytical methods, their occurrence and biosynthesis in plants, and the biological activities and implications in human health. The discussions are focused on important and most recent advances in the above aspects, and challenges are identified for future research.

S. Houten, S. Violante, F. V. Ventura et al.

C. Szabó, H. Ischiropoulos, R. Radi

B. Halliwell

M. Herman

J. Stamler, D. Singel, J. Loscalzo

G. Whitesides, E. Ostuni, S. Takayama et al.

B. Halkier, J. Gershenzon

M. Lesser

R. Iler

A. Bianco, Domenico Salvatore, B. Gereben et al.

A. Milani, Marzieh Basirnejad, Sepideh Shahbazi et al.

Carotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation‐related proteins, retinoid‐like receptors, antioxidant response element, nuclear receptors, AP‐1 transcriptional complex, the Wnt/β‐catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B‐ and T‐lymphocytes, the activity of macrophages and cytotoxic T‐cells, effector T‐cell function and the production of cytokines. Recently, the beneficial effects of carotenoid‐rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β‐carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time‐ and dose‐dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action.

Ø. M. Andersen, K. R. Markham

G. Ferrer-Sueta, Nicolás Campolo, M. Trujillo et al.

G. Brouhard, L. Rice

S. Bartesaghi, R. Radi

In this review we provide an analysis of the biochemistry of peroxynitrite and tyrosine nitration. Peroxynitrite is the product of the diffusion-controlled reaction between superoxide (O2•-) and nitric oxide (•NO). This process is in competition with the enzymatic dismutation of O2•- and the diffusion of •NO across cells and tissues and its reaction with molecular targets (e.g. guanylate cyclase). Understanding the kinetics and compartmentalization of the O2•- / •NO interplay is critical to rationalize the shift of •NO from a physiological mediator to a cytotoxic intermediate. Once formed, peroxynitrite (ONOO- and ONOOH; pKa = 6,8) behaves as a strong one and two-electron oxidant towards a series of biomolecules including transition metal centers and thiols. In addition, peroxynitrite anion can secondarily evolve to secondary radicals either via its fast reaction with CO2 or through proton-catalyzed homolysis. Thus, peroxynitrite can participate in direct (bimolecular) and indirect (through secondary radical intermediates) oxidation reactions; through these processes peroxynitrite can participate as cytotoxic effector molecule against invading pathogens and/or as an endogenous pathogenic mediator. Peroxynitrite can cause protein tyrosine nitration in vitro and in vivo. Indeed, tyrosine nitration is a hallmark of the reactions of •NO-derived oxidants in cells and tissues and serves as a biomarker of oxidative damage. Protein tyrosine nitration can mediate changes in protein structure and function that affect cell homeostasis. Tyrosine nitration in biological systems is a free radical process that can be promoted either by peroxynitrite-derived radicals or by other related •NO-dependent oxidative processes. Recently, mechanisms responsible of tyrosine nitration in hydrophobic biostructures such as membranes and lipoproteins have been assessed and involve the parallel occurrence and connection with lipid peroxidation. Experimental strategies to reveal the proximal oxidizing mechanism during tyrosine nitration in given pathophysiologically-relevant conditions include mapping and identification of the tyrosine nitration sites in specific proteins.

Y. Li-Beisson, J. Thelen, Eric T. Fedosejevs et al.

Algal lipid metabolism fascinates both scientists and entrepreneurs due to the large diversity of fatty acyl structures that algae produce. Algae have therefore long been studied as sources of genes for novel fatty acids; and, due to their superior biomass productivity, algae are also considered a potential feedstock for biofuels. However, a major issue in a commercially viable "algal oil-to-biofuel" industry is the high production cost, because most algal species only produce large amounts of oils after being exposed to stress conditions. Recent studies have therefore focused on the identification of factors involved in TAG metabolism, on the subcellular organization of lipid pathways, and on interactions between organelles. This has been accompanied by the development of genetic/genomic and synthetic biological tools not only for the reference green alga Chlamydomonas reinhardtii but also for Nannochloropsis spp. and Phaeodactylum tricornutum. Advances in our understanding of enzymes and regulatory proteins of acyl lipid biosynthesis and turnover are described herein with a focus on carbon and energetic aspects. We also summarize how changes in environmental factors can impact lipid metabolism and describe present and potential industrial uses of algal lipids.

S. Seaver, Filipe Liu, Qizh Zhang et al.

Abstract For over 10 years, ModelSEED has been a primary resource for the construction of draft genome-scale metabolic models based on annotated microbial or plant genomes. Now being released, the biochemistry database serves as the foundation of biochemical data underlying ModelSEED and KBase. The biochemistry database embodies several properties that, taken together, distinguish it from other published biochemistry resources by: (i) including compartmentalization, transport reactions, charged molecules and proton balancing on reactions; (ii) being extensible by the user community, with all data stored in GitHub; and (iii) design as a biochemical ‘Rosetta Stone’ to facilitate comparison and integration of annotations from many different tools and databases. The database was constructed by combining chemical data from many resources, applying standard transformations, identifying redundancies and computing thermodynamic properties. The ModelSEED biochemistry is continually tested using flux balance analysis to ensure the biochemical network is modeling-ready and capable of simulating diverse phenotypes. Ontologies can be designed to aid in comparing and reconciling metabolic reconstructions that differ in how they represent various metabolic pathways. ModelSEED now includes 33,978 compounds and 36,645 reactions, available as a set of extensible files on GitHub, and available to search at https://modelseed.org/biochem and KBase.

Yutaro Hama, Yuko Fujioka, Hayashi Yamamoto et al.

In mammals, autophagosome formation, a central event in autophagy, is initiated by the ULK complex comprising ULK1/2, FIP200, ATG13, and ATG101. However, the structural basis and mechanism underlying the ULK complex assembly have yet to be fully clarified. Here, we predicted the core interactions organizing the ULK complex using AlphaFold, which proposed that the intrinsically disordered region of ATG13 engages the bases of the two UBL domains in the FIP200 dimer via two phenylalanines and also binds the tandem microtubule-interacting and transport domain of ULK1, thereby yielding the 1:1:2 stoichiometry of the ULK1–ATG13–FIP200 complex. We validated the predicted interactions by point mutations and demonstrated direct triad interactions among ULK1, ATG13, and FIP200 in vitro and in cells, wherein each interaction was additively important for autophagic flux. These results indicate that the ULK1–ATG13–FIP200 triadic interaction is crucial for autophagosome formation and provides a structural basis and insights into the regulation mechanism of autophagy initiation in mammals.