Книги з теми "Phosphorylation oxidative"

Mitochondrial disorders are a group of inherited diseases of energy metabolism caused by impairment of mitochondrial function-primarily disorders of the oxidative phosphorylation system but also the more recently described disorders of mitochondrial transport and fission. This review will focus on primary disorders of mitochondrial oxidative phosphorylation. The neurologic system is one of the most profoundly affected by mitochondrial dysfunction and the effects can be varied and widespread. This has led to these diseases being commonly called mitochondrial encephalomyopathies. The heterogeneity of clinical presentation, laboratory findings, neuroimaging findings, pathologic findings, and genetic findings in these diseases make diagnosis extremely difficult. Treatment for mitochondrial disorders is currently lacking a solid evidence base but this is a rapidly expanding area of research.

The pulmonary oxygen uptake (pV̇O2) kinetic response to exercise provides valuable non-invasive insight into the control of oxidative phosphorylation and determinants of exercise tolerance in children and adolescents. Few methodologically robust studies have investigated pV̇O2 kinetics in children and adolescents, but age- and sex-related differences have been identified. There is a clear age-related slowing of phase II pV̇O2 kinetics during heavy and very heavy exercise, with a trend showing during moderate intensity exercise. During heavy and very heavy exercise the oxygen cost is higher for phase II and the pV̇O2 component is truncated in children. Sex-related differences occur during heavy, but not moderate, intensity exercise, with boys having faster phase II pV̇O2 kinetics and a smaller pV̇O2 slow component compared to girls. The mechanisms underlying these differences are likely related to changes in phosphate feedback controllers of oxidative phosphorylation, muscle oxygen delivery, and/or muscle fibre recruitment strategies.

Mitochondrial disease (mtD) is a genetically, biochemically, and clinically heterogeneous group of disorders that arise most commonly from defects in the oxidative phosphorylation or electron transport chain involved in energy metabolism. These patients have an increased risk for cardiac, respiratory, neurologic, and metabolic complications from anesthesia. Consequently, there are several anesthetic considerations for patients with mtD.

Hyperglycaemia is a frequent phenomenon in critically-ill patients, associated with increased morbidity and mortality. Hyperglycaemia results in cellular glucose overload and toxic adverse effects of glycolysis and oxidative phosphorylation, especially in tissues with insulin-independent glucose uptake, and acute hyperglycaemia can exert a variety of negative effects. It is the main side effect of intensive insulin therapy. Both severe and moderate hypoglycaemia are independent risk factors of mortality in critically-ill patients. Prolonged hypoglycaemia induces neuronal damage, but may also have adverse cardiovascular effects. Several risk factors predispose critically-ill patients to hypoglycaemic events. Rapid glucose fluctuations may induce oxidative stress and lead to vascular damage. Glucose complexity is a marker of endogenous glucose regulation. Association between hyperglycaemia and outcome is weaker in diabetic critically-ill patients than in non-diabetic patients. Pre-admission glucose control in diabetic critically-ill patients plays a role in the response to glucose control and mortality.

Mitochondrial disease is a genetically, biochemically, and clinically heterogeneous group of disorders that arise from defects in cellular oxidative phosphorylation, most commonly within the electron transport chain. All mitochondrial diseases involve disruption in energy production; clinical symptoms usually manifest in tissues with high energy demands although all organs may be affected. The extent of disease depends not only on the mitochondrial defect but on the numbers of dysfunctional mitochondria present in each tissue. Despite in vitro evidence that almost every anesthetic agent studied has been shown to decrease mitochondrial function, all anesthetic agents have been used safely. Discussion of the implications of mitochondrial disease for anesthetic management includes preoperative preparation, volatile and intravenous anesthetic agents, avoidance of succinylcholine, risk of malignant hyperthermia, perioperative fluids, and postoperative management.

Maximal intensity is any activity where the exercise-supplying metabolism demonstrates a higher anaerobic ATP yield than the oxidative phosphorylation metabolism. Ethical considerations prevent muscle biopsy techniques in young people, resulting in indirect inferences about anaerobic metabolism during exercise being applied to mostly mechanically derived measurements. These measurements are largely based on cycle ergometry tests like the Wingate test. Compared to aerobic data, maximal-intensity data sets are infrequently published, female data across all age ranges are lacking, and application is limited by a focus on sports performance rather than health. However, regardless of how these data are analysed, children and adolescent performance is inferior to adults. Most studies attempt to explain this from a quantitative muscle (and age) perspective, while explanations of qualitative factors, e.g. hormonal and neuromuscular, have proved elusive. Future studies should focus on the mechanisms underpinning maximal-intensity exercise as an important component of everyday physical activity.

Mitochondrial disease can affect any organ in the body including the kidney. As increasing numbers of patients with mitochondrial disease are either surviving beyond childhood or being diagnosed in adulthood, it is important for all nephrologists to have some understanding of the common renal complications that can occur in these individuals. Mitochondrial proteins are encoded by either mitochondrial or nuclear DNA (mtDNA and nDNA, respectively); therefore, disease causing mutations may be inherited maternally (mtDNA) or autosomally (nDNA), or can arise spontaneously. The commonest renal phenotype in mitochondrial disease is proximal tubulopathy (Fanconi syndrome in the severest cases); however, as all regions of the nephron can be affected, from the glomerulus to the collecting duct, patients may also present with proteinuria, decreased glomerular filtration rate, nephrotic syndrome, water and electrolyte disorders, and renal tubular acidosis. Understanding of the relationship between underlying genotype and clinical phenotype remains incomplete in mitochondrial disease. Proximal tubulopathy typically occurs in children with severe multisystem disease due to mtDNA deletion or mutations in nDNA affecting mitochondrial function. In contrast, glomerular disease (focal segmental glomerulosclerosis) has been reported more commonly in adults, mainly in association with the m.3243A<G point mutation. Co-enzyme Q10 (CoQ10) deficiency has been particularly associated with podocyte dysfunction and nephrotic syndrome in children. Underlying mitochondrial disease should be considered as a potential cause of unexplained renal dysfunction; clinical clues include lack of response to conventional therapy, abnormal mitochondrial morphology on kidney biopsy, involvement of other organs (e.g. diabetes, cardiomyopathy, and deafness) and a maternal family history, although none of these features are specific. The diagnostic approach involves acquiring tissue (typically skeletal muscle) for histological analysis, mtDNA screening and oxidative phosphorylation (OXPHOS) complex function tests. A number of nDNA mutations causing mitochondrial disease have now been identified and can also be screened for if clinically indicated. Management of mitochondrial disease requires a multidisciplinary approach, and treatment is largely supportive as there are currently very few evidence-based interventions. Electrolyte deficiencies should be corrected in patients with urinary wasting due to tubulopathy, and CoQ10 supplementation may be of benefit in individuals with CoQ10 deficiency. Nephrotic syndrome in mitochondrial disease is not typically responsive to steroid therapy. Transplantation has been performed in patients with end-stage kidney disease; however, immunosuppressive agents such as steroids and tacrolimus should be used with care given the high incidence of diabetes in mitochondrial disease.

Prekladaný vysokoškolský učebný text „Bioenergetika“ by mal slúžiť ako úvod do problematiky štúdia v oblasti bioenergetiky. Táto vedná oblast je v súčasnosti vysoko aktuálna, pretože výsledky získané bioenergetickým výskumom v uplynulých rokoch zreteľne ukazujú, že bioenergetické procesy prebiehajúce v živých systémoch neslúžia “len” na transformáciu energie, ale ovplyvňujú aj priebeh procesov ako sú apoptóza, starnutie, vznik a rozvoj mnohých ochorení (predovšetkým neurodegeneratívnych). Tieto skutočnosti jednoznačne naznačujú potrebu existencie kvalitných učebných textov, ktoré by prijateľným spôsobom umožnili študentom získať potrebné informácie a vedomosti v tejto vednej discipline. Z vyššie uvedených dôvodov sme sa rozhodli vytvoriť tieto učebné texty, ktoré sú vo forme desiatich samostatných kapitol, ktoré však na seba prirodzene a logicky nadväzujú. Jedna kapitola predstavuje v podstate jednu prednášku v rámci kurzu Bioenergetiky, ktorý je realizovaný na Prírodovedeckej fakulte Univerzity Pavla Jozefa Šafárika v Košiciach na magisterskom a doktorandskom stupni študijného programu „Biofyzika“. Zároveň tieto texty môžu poslúžiť aj pri výučbe v študijnom predmete Biochémia, ktorý je prednášaný v bakalárskych a magisterských stupňoch študijných programov “Biochémia” resp. “Biofyzika”. Dovoľujeme si vyjadriť presvedčenie, že tieto učebné texty by mohli byť istým spôsobom nápomocné aj vedeckým pracovníkom pracujúcim v oblasti výskumu týkajúcho sa problematiky transformáci energie v biologických organizmoch a fenoménoch spojených s touto transformáciou. V týchto učebných textoch sú postupne uvádzané poznatky týkajúce sa základných konceptov bioenergetiky, mechanizmov procesov ako sú glykolýza a Krebsov cyklus (okrem podrobného a uceleného popis týchto procesov je tu uvedený aj všeobecný náhľad o prepojenosti týchto procesov ako aj ich začlenenie do kompaktného pohľadu na celkový proces transformácie energie v biologických organizmoch), zloženia štruktúry a funkčnosti biologických membrán (táto oblast je nevyhnutná pre lepšie pochopenie poznatkov, ktoré sú uvedené v nasledujúcich kapitolách). V nasledujúcich kapitolách sa učebný text zaoberá popisom štruktúry a funkcie mitochondrií, pričom veľký dôraz je dávaný na popis vlastností a mechanizmov fungovania štyroch komplexov dýchacieho reťazca a ATP-syntázy. Tieto komplexy vytvárajú podmienky pre existenciu “najdôležitejšieho” bioenergetického procesu, oxidatívnej fosforylácie. V záverečných dvoch kapitolách sú uvedené mechanizmy procesov vytvárajúcich fotosyntézu, jej svetlej aj tmavej fázy. Sú tu relevantné informácie o tomto “druhom” najdôležitejšom bioenergetickom procese prebiehajúcom v mnohých biologických organizmoch a poskytujúcom možnosť transformácie enrgie elektromagnetického žiarenia na energiu “ukrytú” v chemických väzbách určitých chemických molekúl. Chceme vyjadriť naše presvedčenie, že predložené učebné texty “Bioenergetika” budú dobrým “pomocníkom a inšpirátorom” pre mnohých študentov, ktorí sa budú chcieť dozvedieť čo najviac o fascinujúcich štruktúrach a mechanizmoch umožňujúcich transformáciu energie v živých systémoch, bez ktorej by nebola možná existencia života ako ho poznáme. Želáme príjemné a podnetné čítanie a štúdium. URL: www.unibook.upjs.sk The textbook "Bioenergetics" should serve as an introduction to the study of bioenergetics. This field of science is currently highly actual, as the results of the bioenergetics research in recent years clearly show that bioenergetics processes in living systems can "serve" not only to transformation of energy, but also affect the course of processes such as apoptosis, aging, origin and development of many diseases (especially neurodegenerative). These facts clearly indicate the need for the existence of quality teaching texts that would allow students to acquire the necessary information and knowledge in this scientific discipline in an acceptable way. For the above mentioned reasons, we decided to create these textbooks, which are in the form of ten chapters, which naturally and logically follow each other. One chapter basically presents one lecture within the course of Bioenergetics, which is realized at the Faculty of Science of the Pavel Jozef Šafárik University in Košice at the master's and doctoral degree of the study program "Biophysics". At the same time, these texts can also be used for teaching in the study subject Biochemistry, which is taught in the bachelor's and master's degree programs of the study programs "Biochemistry" resp. “Biophysics”. We would like to express our conviction that these textbooks could in some way also help researchers working in the field of the energy transformation in biological organisms and the phenomena associated with this transformation. These textbooks present knowledge about the basic concepts of bioenergetics, the mechanisms of processes such as glycolysis and the Krebs cycle (in addition to a detailed and comprehensive description of these processes, there is also a general view of the interconnectedness of these processes and their incorporation into a compact view of the overall energy transformation in biological organisms), the structure and functionality of biological membranes (this area is necessary for a better understanding of the knowledge presented in the following chapters). In the following chapters, the textbook deals with the description of the structure and function of mitochondria, with great emphasis on the properties and mechanisms of functioning of the four complexes of the respiratory chain and ATP-synthase. These complexes create the basis for the existence of the "most important" process in bioenergetics, oxidative phosphorylation. In the final two chapters, the mechanisms of the processes that produce photosynthesis, its light and dark phases, are presented. There is relevant information about this "second" most important bioenergetics process taking place in many biological organisms and providing the possibility of transforming the energy of electromagnetic radiation into energy "hidden" in the chemical bonds of certain chemical molecules. We want to express our conviction that the textbooks "Bioenergetics" will be a good "helper and inspirer" for many students who want to learn as much as possible about the fascinating structures and mechanisms for energy transformation in living systems, without which it would not be possible existence of life as we know it.