Carboxylic acid transporters form a heterogeneous group of proteins, presenting diverse mechanisms of action and regulation, and belonging to several different families. Multiple physiological and genetic studies in several organisms, from yeast to mammals, have allowed the identification of various genes coding for carboxylate transporters. Detailed understanding of the metabolism and transport of these nutrients has become more important than ever, both from a fundamental and from an applied point of view. Under a biotechnological perspective, the increasing economic value of these compounds has boosted this field of research considerably. Here we review the current knowledge on yeast carboxylate transporters, at the biochemical and molecular level, focusing also on recent biotechnological developments.
This review underlines the need for a careful prescription of tramadol and tapentadol. Although both are widely prescribed synthetic opioid analgesics, their toxic effects and potential dependence are not completely understood yet. In particular, concerning tapentadol, further research is needed to better assess its toxic effects.
Tramadol and tapentadol are centrally acting, synthetic opioid analgesics used in the treatment of moderate to severe pain. Main metabolic patterns for these drugs in humans are well characterized. Tramadol is mainly metabolized by cytochrome P450 CYP2D6 to O-desmethyltramadol (M1), its main active metabolite. M1 and tapentadol undergo mainly glucuronidation reactions. On the other hand, the pharmacokinetics of tramadol and tapentadol are dependent on multiple factors, such as the route of administration, genetic variability in pharmacokinetic components and concurrent consumption of other drugs. This review aims to comparatively discuss the metabolomics of tramadol and tapentadol, namely by presenting all their known metabolites. An exhaustive literature search was performed using textual and structural queries for tramadol and tapentadol, and associated known metabolizing enzymes and metabolites. A thorough knowledge about tramadol and tapentadol metabolomics is expected to provide additional insights to better understand the interindividual variability in their pharmacokinetics and dose-responsiveness, and contribute to the establishment of personalized therapeutic approaches, minimizing side effects and optimizing analgesic efficacy.
Altered metabolism, associated with acidification of the extracellular milieu, is one of the major features of cancer. As pH regulation is crucial for the maintenance of all biological functions, cancer cells rely on the activity of lactate exporters and proton transporters to regulate their intracellular pH. The major players in cancer pH regulation are proton pump ATPases, sodium-proton exchangers (NHEs), monocarboxylate transporters (MCTs), carbonic anhydrases (CAs) and anion exchangers (AEs), which have been shown to be upregulated in several human malignancies. Thanks to the activity of the proton pumps and transporters, tumours acidify their microenvironment, becoming more aggressive and resistant to therapy. Thus, targeting tumour pH may contribute to more effective anticancer strategies for controlling tumour progression and therapeutic resistance. In the present study, we review the role of the main pH regulators expressed in human cancer cells, including their diagnostic and prognostic value, as well as their usefulness as therapeutic targets.
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