New mathematical derivations for calculation of ATP yield due to the complete oxidation of different types of fatty acids.

During the complete oxidation of fatty acids, the electrons removed from fatty acids in different forms (FADH2 and NADH2) pass through the respiratory chain, driving the ATP synthesis. Generally, the ATP yield due to the complete oxidation of fatty acids is calculated by sum total the ATPs obtained due to the oxidation of FADH2 and NADH2 due to lack of any particular method. This calculation is simple for saturated even numbered fatty acids, but in the case of saturated and unsaturated odd numbered fatty acids the calculation of ATP yield is difficult and needs mathematical calculations due to some changes in their β-oxidation pathway when compared to the pathway of saturated even numbered fatty acids. These calculations are made simple by our derivations and following formulae where we require only number of carbon atoms and double bonds present in a fatty acid. Our method is superior and easier in comparison to long mathematical calculations that are in the practice.

Secretion of adenylate kinase 1 is required for extracellular ATP synthesis in C2C12 myotubes

Extracellular ATP (exATP) has been known to be a critical ligand regulating skeletal muscle differentiation and contractibility. ExATP synthesis was greatly increased with the high level of adenylate kinase 1 (AK1) and ATP synthase beta during C2C12 myogenesis. The exATP synthesis was abolished by the knock-down of AK1 but not by that of ATP synthase beta in C2C12 myotubes, suggesting that AK1 is required for exATP synthesis in myotubes. However, membrane-bound AK1beta was not involved in exATP synthesis because its expression level was decreased during myogenesis in spite of its localization in the lipid rafts that contain various kinds of receptors and mediate cell signal transduction, cell migration, and differentiation. Interestingly, cytoplasmic AK1 was secreted from C2C12 myotubes but not from C2C12 myoblasts. Taken together all these data, we can conclude that AK1 secretion is required for the exATP generation in myotubes.

Obstructive jaundice induces early depression of mitochondrial respiration in rat hepatocytes

INTRODUCTION: Oxidative phosphorylation dysfunction of hepatocyte mitochondria is involved in the pathophysiology of organ dysfunction following obstructive jaundice (OJ). However the time period from biliary occlusion to the occurrence of the dysfunction has not been determined decisively. PURPOSE: To evaluate the early effects (1 d and 7 d) of OJ on liver mitochondria respiratory function in rats. METHODS: Male Wistar rats (200-250 g) were randomly divided into the following 3 groups: laparotomy plus OJ for 24 h (1d group) (n = 10); laparotomy plus OJ for 7 d (7d group) (n = 10); sham control procedure (CTR group) (n = 12). At the end of OJ periods, total serum bilirubin level, hepatic enzyme activity levels (GOT, GTP, Gama-GT, ALP), mitochondrial respiration phases S3 and S4, as well as the respiratory control ratio (RC = S3/S4), and ADP consumption/oxygen consumption (ADP/O) ratio, were determined. RESULTS: Total serum bilirubin, activity of most hepatic enzymes, and O2 consumption during basal (S4) respiration were increased in the 1d and 7d groups (ANOVA, p = 0.05 vs. CTR). After ADP addition, the O2 consumption rate (S3) in the 1d group remained similar to the CTR rate (ANOVA p > .05), while the RC rate was reduced (ANOVA, p = 0.001) vs. CTR. The effects observed on mitochondrial respiration in the 1d group were exacerbated in the 7d group. CONCLUSION: These results indicate that OJ induces early (24 h) depression of liver mitochondria respiration, and thus may lead to early reduction in the production of high energy bonds.

INTRODUÇÃO: A disfunção da fosforilação oxidativa das mitocôndrias do hepatócito está envolvida na fisiopatologia da disfunção orgânica subseqüente à icterícia obstrutiva (IO). Entretanto, a precocidade da ocorrência desta disfunção permanece obscura. OBJETIVO: Avaliar o efeito precoce da IO na função respiratória mitocondrial em ratos. MÉTODOS: Ratos Wistar machos (200 a 250g) foram randomizados em 3 grupos que foram submetidos a laparotomia mais: IO por 24hs (grupo 1d)(n=10); IO por 7 dias (grupo 7d)(n=10; procedimento simulado (grupo CTR)(n=12). Ao final dos períodos de IO, foram determinados: bilirrubina sérica total, atividade de enzimas hepáticas (TGO, TGP, Gama-GT, FA), e as fases S3 e S4 da respiração mitocondrial, bem como o razão do controle respiratório (RC = S3/S4), e a razão entre consumo de ADP/consumo de oxigênio (ADP/O). RESULTADOS: Observou-se significativo aumento de bilirrubina sérica total, enzimas hepáticas, e consumo de O2 durante a respiração basal (S4) no grupo de IO por 24hs (ANOVA, p=0.009). Após adição de ADP, a taxa de consumo de O2 (S3) não diminuiu significativamente no grupo de IO, comparado com o CTR (ANOVA, p>0.05); entretanto, a razão do controle respiratório (RC) foi significativamente mais baixa comparada com o CTR (ANOVA, p=0.001). Os efeitos observados na respiração mitocondrial no grupo do dia 1d estavam exacerbados no grupo 7d. CONCLUSÃO: Estes resultados indicam que a icterícia obstrutiva induz depressão precoce (24hs) da respiração mitocondrial, e pode assim levar à redução da produção de ligações de alta energia.

Energy interconversion by the sarcoplasmic reticulum Ca2+-ATPase: ATP hydrolysis, Ca2+ transport, ATP synthesis and heat production

The sarcoplasmic reticulum of skeletal muscle retains a membrane bound Ca2+-ATPase which is able to interconvert different forms of energy. A part of the chemical energy released during ATP hydrolysis is converted into heat and in the bibliography it is assumed that the amount of heat produced during the hydrolysis of an ATP molecule is always the same, as if the energy released during ATP cleavage were divided in two non-interchangeable parts: one would be converted into heat, and the other used for Ca2+ transport. Data obtained in our laboratory during the past three years indicate that the amount of heat released during the hydrolysis of ATP may vary between 7 and 32 Kcal/mol depending on whether or not a transmembrane Ca2+ gradient is formed across the sarcoplasmic reticulum membrane. Drugs such as heparin and dimethyl sulfoxide are able to modify the fraction of the chemical energy released during ATP hydrolysis which is used for Ca2+ transport and the fraction which is dissipated in the surrounding medium as heat.

Hormônios tireóideos, UCPs e termogênese / Thyroid hormones, UCPs and termogenesis

Calor é um subproduto da transformação de energia, em suas diversas formas, durante a síntese e a utilização do ATP. Nos animais homeotérmicos, o calor derivado das funções biológicas - estando o organismo em repouso e à temperatura ambiente - é utilizado para manter o organismo próximo a 37ºC. Essa termogênese obrigatória está associada à ineficiência termodinâmica intrínseca mitocondrial, derivada da presença de proteínas desacopladoras (UCPs, uncoupling proteins). Durante a exposição ao frio, o organismo é capaz de gerar mais calor através da termogênese facultativa, por processos que também envolvem UCPs. Os hormônios tireóideos influenciam diretamente a expressão da UCP-1 e, indiretamente, a expressão das UCP-2 e UCP-3. Além disso, também aceleram o turnover de várias reações ou vias metabólicas cíclicas que levam a maior gasto de ATP e produção de calor.

Alternative mitochondrial functions in cell physiopathology: beyond ATP production

It is well known that mitochondria are the main site for ATP generation within most tissues. However, mitochondria also participate in a surprising number of alternative activities, including intracellular Ca2+ regulation, thermogenesis and the control of apoptosis. In addition, mitochondria are the main cellular generators of reactive oxygen species, and may trigger necrotic cell death under conditions of oxidative stress. This review concentrates on these alternative mitochondrial functions, and their role in cell physiopathology

Considerações sobre exercício físico, creatina e nutrição / Physical exercise, creatine and nutrition: a review

Creatina é um nutriente natural, encontrado em alimento de origem animal, como carnes e peixes, sendo também sintetizada endogenamente no fígado, pâncreas e rins, a partir dos aminoácidos glicina, arginina e metionina. A creatina total (TCr) existente no músculo apresenta-se em duas formas: creatina livre (Cr) e fosfocreatina (PCr). Creatina é importante reservatório de energia para a contração muscular, pois pode sofrer fosforilação, formando fosfocreatina e, reversivelmente, pode doar o grupo fosfato para adenosina difosfato (ADP) com a finalidade de sintetizar adenosina trifosfato (ATP). Esta reação é fonte rápida de energia para o desempenho de atividades físicas de alta intensidade e curta duração...

ATP y metabolismo cardiaco: acerca del tratamiento metabólico del infarto agudo del miocardio / ATP and cardiac metbolism: about metabolic treatment of acute cardiac infarction

Investigaciones sobre el ATP han revelado principios fundamentales de biología molecular cuyos descubridores fueron galardonados con el premio Nobel de química en 1997. En este artículo se revisan avances recientes sobre síntesis e hidrólisis del ATP y su relación con el metabolismo cardiaco. La síntesis de ATP se debe a la enzima F0 F1 sintetasa (o H+-ATP sintetasa) acoplada con la fuerza electromotriz de un gradiente de protones (H+) generado por fotosíntesis o por fosforilación oxidativa. Al pasar por FO, la corriente de H+ produce rotación interna de la subunidad ß y catálisis rotativa de las tres subunidades ß de F1. La rotación de la subunidad ç ha sido demostrada directamante. La hidrólisis de ATP está acoplada con la función de bombas iónicas (ATPasas) dependientes del aporte continuo de sangre oxigenada al cerebro y corazón. Al disminuir el aporte de O2, se produce zonas heterogéneas de metabolismo anaeróbico con acumulación de radicales libres y formación de productos tóxicos. A últimas fechas, hay un renovado interés para el tratamiento metabólico del infarto agudo del miocardio

Estudo da inativaçäo da glicoamilase e da influência de fosfatos na produçäo da enzima em cultivos de Aspergillus awamori / Study of inactivation of glucoamylase and of the influence of phosphates in the production of enzymes in cultures of Aspergillus awamori

A produçäo de glicoamilase pelo fungo Aspergillus awamori NRRI 3112 utilizando um meio contendo farinha de mandioca foi estudada. Este trabalho objetivou identificar a/s causa/s da inativaçäo da glicoamilase e verificar a influência de fosfatos no metabolismo fúngico, particularmente aqueles relacionados com a produçäo da glicoamilase. Para estudar a perda de atividade da glicoamilase, testes de inativaçäo ácida foram efetuados e a açäo de proteases ácidas foi determinada em cultivos em incubador e reator. O papel de fosfatos na produçäo da glicoamilase também foi investigado em incubador e reator. Foram efetuados cultivos em frascos contendo uma concentraçäo inicial de substrato (S IND.0) de 20 g de açúcares redutores totais (ART) e fosfatos fornecendo concentraçöes de 1,14, 2,28, 3,42 e 4,56 g de fósforo total por litro...

Ca2+ transport and oxidative damage of mitochondria

1. Mitochondria from a wide range of sources have the ability to accumulate Ca2+ down their electrochemical gradient mediated by a uniport mechanism. 2. Ca2+ efflux occurs via two separate pathways: a Na+/Ca2+ exchanger that predominates in mitochondria from excitable tissues and a Na(+)-independent pathway that predominates in mitochondria from non-excitable tissues. 3. The kinetic characteristics of these calcium influx-efflux pathways appear to be incompatible with any role for mitochondria as cytosolic Ca2+ buffers, under resting normal physiological conditions. Instead, the biological role of this Ca(2+)-transporting system seems to be the regulation of matrix Ca2+ in a range that permits the regulation of three intramitochondrial Ca(2+)-dependent dehydrogenases which catalyze rate-limiting reactions of the Krebs cycle. 4. Under conditions in which a high cytosolic Ca2+ concentration is sustained, the matrix Ca2+ concentration may attain levels that lead to impairment of mitochondrial functions such as inhibition of oxidative phosphorylation and increase in inner membrane permeability. 5. Accumulation of Ca2+ by mitochondria under conditions of oxidative stress induces an increase in inner membrane permeability by a mechanism that appears to be mediated by protein polymerization due to thiol cross-linking

Oxidative metabolism and body weight: inactive, active, and mitochondrial volumes

In homeotherms, the standardized (basal) metabolic rate should not be expressed per kilogram of body weight (specific metabolic rate), nor per unit of body surface (square meters of body-ambient interface), since both mitochondrial thermogenesis and heat-loss mechanisms (radiation, conduction, convection, evaporation) are not uniform processes. On the contrary, each organism is an heterogeneous bioreactor, which is composed at least of two compartments: 1) a metabolically active volume (aV), where oxidative phosphorylation takes place; and 2) a metabolically inactive volume (iV), where oxygen consumption is negligible. The ratio (aV/iV) is not invariant, since iV increases disproportionately with the scaling up of body size, and as shown by us, when the three main components of iV, i.e., skeleton, fat deposits, and blood volume, are added together, a similar disproportionality is found. The aV was determined by subtracting the iV from the total volume (V) of an organism, or by estimating the volume occupied by all mitochondria, or mitochondrial volume (mtV). For this purpose two procedures are discussed: 1) the stereological or morphometric method; and 2) the oxygen consumption per unit time or physiometric method. The latter procedure is based on the equivalence between an VO2 = 3 ml O2.min-1 and a mtV of 1 ml, whose oxidative phosphorylation yields an approximate power output of 1 watt. The correspondence between oxygen consumption, heat production, and electron flux at the respiratory chain of the mitochondrial cristae, is discussed. From a physical point of view, the metabolic rate is a ®power® function (P = M L2T-3), where M = mass, L = length, and T = time. The dimensional analysis and the statistical treatment of the corresponding numerical values of more than 200 allometric equations yields the 3/4 power, law established by Kleiber (1961), for the relationship between basal metabolism and body weight. Instead of expressing the metabolic rate per unit body weight (kg-1) or per unit body surface (m-2) structural and functional criteria should be taken into account as, for instance, the distinction between iV and aV, and particularly by emphasizing the paramount importance of the mtV where oxidative phosphorylation takes place. An allometric equation relating mtV and body weight (W) could be tentatively established for interspecies comparisons

Metabolic studies on mycobacteria. V. A preliminary report on the ATP synthesis by mycobacteria including M. leprae by using different substrates.

By deletion and addition of various substrates in Sauton's and Dubos media, an experimental system has been standardised in which the role of various nutrients in the energy synthesis of mycobacteria can be determined. By using this system with cultivable mycobacteria it was observed that glycerol and asparagine are the important ingredients for ATP synthesis by mycobacteria. Glucose further enhanced the ATP synthesis and growth of these mycobacteria. In the media containing asparagine or glycerol, there was marginal increase in the ATP in the M. leprae suspensions initially but this was not sustained and there was no progressive increase in biomass or multiplication. When M. leprae was incubated in the media from which both these substrates were deleted, there was progressive decline in ATP levels right from the beginning. From these preliminary results, it appears that asparagine and glycerol may be useful as substrates for ATP synthesis by M. leprae and need to be investigated further. In depth studies are necessary to find out the factors which results in the inability of M. leprae to utilise these and other substrates in a substrained manner for its multiplication and growth in artificial media.