Nuclear Encoded Mitochondrial Proteins in Metabolite Transport and Oxidation Pathway Connecting Metabolism of Nutrients

In the mitochondria, there are ongoing processes essential to the survival of cells associated with the production of energy ending in the oxidative phosphorylation and the formation of ATP, constituting a form of energy for majority of metabolic processes. Except for nutrient oxidation in the citric acid cycle interfacing with the process of oxidative phosphorylation, mitochondria are linked to a number of metabolic pathways ongoing directly in mitochondria or indirectly in cell compartments by serving substrates. Mitochondrial activities maintenance requires continual draw of intermediates from cytosol through the double mitochondrial membrane as well as transport in the reverse direction. Interconnection and regulation of all the processes are mediated by transporters and carriers, activities of which are affected by cell and body requirements. In the chapter, the main transport systems localized in membranes of mitochondria, their regulation, affection, and disorders in the background of mitochondria aberrant functions are described. Voltage-dependent anion channels, translocase of mitochondrial outer membrane, deoxynucleotide carrier, ADP/ATP nucleotide translocase, and phosphate carrier in mitochondrial inner membrane are among them. In more detail, the pyruvate carrier and its abnormal activity, but also others as di- and tri-carboxylate, glutamate, and ornithine carriers, are characterized. The uncoupling protein, as solute carrier family members, involvement is also mentioned

Cytogenetic Analysis of Selected Genetically Determined Diseases in Eastern Slovakia

This work presents the results of cytogenetic analysis performed during the period 1990-2021. The work focuses on cytogenetic analysis of selected diseases that represent a serious medical and social problem in the Prešov region of east¬ern Slovakia. The analysis also included the determination of cytogenetic and molecular-genetic marker frequency re¬lated to selected clinical genetic diseases in a specified population of Roma ethnicity. Chromosome analysis confirmed a wide spectrum of chromosomal aberrations in patients with Down’s syndrome and Turner syndrome, revealing a spectrum of aberrations from monosomy X, isochromosome Xq, and deletions Xp to marker chromosomes. Chromosomal aberrations cause 5.5% of fertility disorders in couples, with numerical and structural chromosomal aberrations found in 2.1 and 3.4% respectively, revealing a risk finding for offspring of carriers of balanced translocations. Microdeletions, combined microdeletions (AZFb,c) and complete deletion of the AZF region of the Y chromosome were found in men diagnosed with azoospermia. In addition, pathological karyotypes were detected in men and women (13 and 10%). Another set of analyses in patients with onco-haematological diseases revealed presence of Philadelphia chromosome (Ph1) in 94.4% of patients with chronic myeloid leukaemia, complex translocation of chromosomes 8, 9, 22; mosaic karyotype of Ph1. Chromosomal aberrations in patients with myelodysplastic syndrome also included also atypical and as yet unpublished cytogenetic markers. Myeloproliferative diseases were detected in 28.3% of patients with heterogenous chromosomal aberrations. Revelations from cytogenetic analysis enable improvement in the efficiency of health care, diagnostics, therapeutic sig¬nificance and prognosis of affected people in the majority population and Roma minority in this region of Slovakia

Medicinal Chemistry

The area covered by this book undoubtedly includes a multidisciplinary approach. It combines and uses the wide range of methods and knowledge from a variety of disciplines in chemistry, pharmacology, and biology to synthesize new or extracted natural substances and their characterization, in terms of bioefficiency in different systems, pharmacokinetics, and pharmacodynamics. Importance is placed on revealing the interactions and effects on organisms. The process is long term, ranging from synthesis to potential testing of substances in animal studies, followed by monitoring effects on patients. The purpose is to define molecular targets of the highest efficacy of the prepared drugs, minimizing the undesirable effects. The content of this book is conceived with these intentions

Organometallic iron complexes as potential cancer therapeutics

Metal-containing drugs have long been used for medicinal purposes in more or less empirical way. The potential of these anticancer agents has only been fully realised and explored since the discovery of the biological activity of cisplatin. Cisplatin and carboplatin have been two of the most successful anti-cancer agents ever developed, and are currently used to treat ovarian, lung and testicular cancers. They share certain side effects, so their clinical use is severely limited by dose-limiting toxicity. Inherent or acquired resistance is a second problem often associated with platinum-based drugs, with further limits of their clinical use. These problems have prompted chemists to employ different strategies in development of the new metal-based anticancer agents with different mechanisms of action. There are various metal complexes still under development and investigation for the future cancer treatment use. In the search for novel bio-organometallic molecules, iron containing anti-tumoral agents are enjoying an increasing interest and appear very promising as the potential drug candidates. Iron, as an essential cofactor in a number of enzymes and physiological processes, may be less toxic than non essential metals, such as platinum. Up to now, some of iron complexes have been tested as cytotoxic agents and found to be endowed with an antitumor activity in several in vitro tests (on cultured cancer cell lines) and few in vivo experiments (e. g. on Ehrlich's ascites carcinoma). Although the precise molecular mechanism is yet to be defined, a number of observations suggest that the reactive oxygen species can play important role in iron-induced cytotoxicty. This review covers some relevant examples of research on the novel iron complexes

Oxidative Stress and Opioids

In recent years, research has shown the involvement of free radicals in the development of the pain that accompanies many pathological conditions. In the treatment of acute and chronic pain, the most effective therapies are natural and synthetic opioid alkaloids. Their metabolism in itself may contribute to the formation of free radicals and thus affect body system load and the perception of pain. Long-term treatment with opioids is a tool of choice for the treatment of medium and severe pain. Opioids stimulate the effect of endogenous opioids, endorphins, by binding to multiple subtypes of opioid receptors (μ,κ,σ) in spinal, supraspinal and peripheral tissues. Morphine is a typical, natural opioid analgesic utilised in practice in the treatment of severe chronic pain. In addition, similar effects can be expected from semisynthetic opioids such as oxycodone and hydromorphone. However, during treatment with opioids some adverse effects can appear regardless of whether treatment is short-term or long-term. One potentially serious side effect is the induction of oxidative stress. The purpose of this present work is to determine the main sources of reactive oxygen and nitrogen in the development of infl ammatory and neuropathic pain, and the manner in which metabolism of morphine contributes to oxidative stress alone.</p

Organometallic iron complexes as potential cancer therapeutics

Metal-containing drugs have long been used for medicinal purposes in more or less empirical way. The potential of these anticancer agents has only been fully realised and explored since the discovery of the biological activity of cisplatin. Cisplatin and carboplatin have been two of the most successful anti-cancer agents ever developed, and are currently used to treat ovarian, lung and testicular cancers. They share certain side effects, so their clinical use is severely limited by dose-limiting toxicity. Inherent or acquired resistance is a second problem often associated with platinum-based drugs, with further limits of their clinical use. These problems have prompted chemists to employ different strategies in development of the new metal-based anticancer agents with different mechanisms of action. There are various metal complexes still under development and investigation for the future cancer treatment use. In the search for novel bio-organometallic molecules, iron containing anti-tumoral agents are enjoying an increasing interest and appear very promising as the potential drug candidates. Iron, as an essential cofactor in a number of enzymes and physiological processes, may be less toxic than non essential metals, such as platinum. Up to now, some of iron complexes have been tested as cytotoxic agents and found to be endowed with an antitumor activity in several in vitro tests (on cultured cancer cell lines) and few in vivo experiments (e. g. on Ehrlich's ascites carcinoma). Although the precise molecular mechanism is yet to be defined, a number of observations suggest that the reactive oxygen species can play important role in iron-induced cytotoxicty. This review covers some relevant examples of research on the novel iron complexes

Glutathione-Related Enzymes and Proteins: A Review

The tripeptide glutathione is found in all eukaryotic cells, and due to the compartmentalization of biochemical processes, its synthesis takes place exclusively in the cytosol. At the same time, its functions depend on its transport to/from organelles and interorgan transport, in which the liver plays a central role. Glutathione is determined as a marker of the redox state in many diseases, aging processes, and cell death resulting from its properties and reactivity. It also uses other enzymes and proteins, which enables it to engage and regulate various cell functions. This paper approximates the role of these systems in redox and detoxification reactions such as conjugation reactions of glutathione-S-transferases, glyoxylases, reduction of peroxides through thiol peroxidases (glutathione peroxidases, peroxiredoxins) and thiol–disulfide exchange reactions catalyzed by glutaredoxins