Balanced Biochemical Reactions: A New Approach to Unify Chemical and Biochemical Thermodynamics

A novel procedure is presented which, by balancing elements and electric charge of biochemical reactions which occur at constant pH and pMg, allows assessing the thermodynamics properties of reaction ΔrG′0, ΔrH′0, ΔrS′0 and the change in binding of hydrogen and magnesium ions of these reactions. This procedure of general applicability avoids the complex calculations required by the use of the Legendre transformed thermodynamic properties of formation ΔfG′0, ΔfH′0 and ΔfS′0 hitherto considered an obligatory prerequisite to deal with the thermodynamics of biochemical reactions. As a consequence, the term “conditional” is proposed in substitution of “Legendre transformed” to indicate these thermodynamics properties. It is also shown that the thermodynamic potential G is fully adequate to give a criterion of spontaneous chemical change for all biochemical reactions and then that the use of the Legendre transformed G′ is unnecessary. The procedure proposed can be applied to any biochemical reaction, making possible to re-unify the two worlds of chemical and biochemical thermodynamics, which so far have been treated separately

Increase of free Mg(2+ )in the skeletal muscle of chronic fatigue syndrome patients

In a previous study we evaluated muscle blood flow and muscle metabolism in patients diagnosed with chronic fatigue syndrome (CFS). To better understand muscle metabolism in CFS, we re-evaluated our data to calculate free Magnesium levels in skeletal muscle. Magnesium is an essential cofactor in a number of cell processes. A total of 20 CFS patients and 11 controls were evaluated. Phosphorus magnetic resonance spectroscopy from the medial gastrocnemius muscle was used to calculate free Mg(2+ )from the concentrations and chemical shifts of Pi, PCr, and beta ATP peaks. CFS patients had higher magnesium levels in their muscles relative to controls (0.47 + 0.07 vs 0.36 + 0.06 mM, P < 0.01), although there was no difference in the rate of phosphocreatine recovery in these subjects, as reported earlier. This finding was not associated with abnormal oxidative metabolism as measured by the rate of recovery of phosphocreatine after exercise. In summary, calculation of free Mg(2+ )levels from previous data showed CFS patients had higher resting free Mg(2+ )levels compared to sedentary controls

Chemical and biochemical thermodynamics reunification (IUPAC Technical Report)

Abstract According to the 1994 IUBMB-IUPAC Joint Commission on Biochemical Nomenclature (JCBN) on chemical and biochemical reactions, two categories of thermodynamics, based on different concepts and different formalisms, are established: (i) chemical thermodynamics, which employ conventional thermodynamic potentials to deal with chemical reactions [1], [2], [3]; and (ii) biochemical thermodynamics, which employ transformed thermodynamic quantities to deal with biochemical reactions based on the formalism proposed by Alberty [4], [5], [6], [7]. We showed that the two worlds of chemical and biochemical thermodynamics, which so far have been treated separately, can be reunified within the same thermodynamic framework. The thermodynamics of chemical reactions, in which all species are explicitly considered with their atoms and charge balanced, are compared with the transformed thermodynamics generally used to treat biochemical reactions where atoms and charges are not balanced. The transformed thermodynamic quantities suggested by Alberty are obtained by a mathematical transformation of the usual thermodynamic quantities. The present analysis demonstrates that the transformed values for Δr G′0 and Δr H′0 can be obtained directly, without performing any transformation, by simply writing the chemical reactions with all the pseudoisomers explicitly included and the elements and charges balanced. The appropriate procedures for computing the stoichiometric coefficients for the pseudoisomers are fully explained by means of an example calculation for the biochemical ATP hydrolysis reaction. It is concluded that the analysis reunifies the "two separate worlds" of conventional thermodynamics and transformed thermodynamics

Monitoring magnesium efflux cyclic AMP-induced in HL60 cells by using a new hydroxyquinoline fluorescent chemosensor

Cellular homeostasis of magnesium is still unclear. Several studies documented the occurrence of fluxes of magnesium across the plasmamembrane within minutes from the application of metabolic or hormonal stimuli. These fluxes, however, result in limited variation of free Mg2+ intracellular concentration and large changes in total Mg content. It has been reported that a stimulation with cyclic AMP caused a movement of total magnesium within 10 min after treatment in cardiomyocytes. In this study we tested this hypothesis in HL60 leukemic cells, not excitable but highly proliferating cell model. We evaluated Mg flux by DCHQ5, the phenyl-derivative of hydroxyquinoline fluorescent probe family. We observed a drastic decrease of intracellular total magnesium in the first 3 min. We also verified that at least 10% of the total intracellular amount of magnesium moved in the supernatant of stimulated cells

Free Mg(2+ )concentration in the calf muscle of glycogen phosphorylase and phosphofructokinase deficiency patients assessed in different metabolic conditions by (31)P MRS

BACKGROUND: The increase in cytosolic free Mg(2+ )occurring during exercise and initial recovery in human skeletal muscle is matched by a decrease in cytosolic pH as shown by in vivo phosphorus magnetic resonance spectroscopy ((31)P MRS). To investigate in vivo to what extent the homeostasis of intracellular free Mg(2+ )is linked to pH in human skeletal muscle, we studied patients with metabolic myopathies due to different disorders of glycogen metabolism that share a lack of intracellular acidification during muscle exercise. METHODS: We assessed by (31)P MRS the cytosolic pH and free magnesium concentration ([Mg(2+)]) in calf muscle during exercise and post-exercise recovery in two patients with McArdle's disease with muscle glycogen phosphorylase deficiency (McArdle), and two brothers both affected by Tarui's disease with muscle phosphofructokinase deficiency (PFK). RESULTS: All patients displayed a lack of intracellular acidosis during muscle exercise. At rest only one PFK patient showed a [Mg(2+)] higher than the value found in control subjects. During exercise and recovery the McArdle patients did not show any significant change in free [Mg(2+)], while both PFK patients showed decreased free [Mg(2+)] and a remarkable accumulation of phosphomonoesters (PME). During initial recovery both McArdle patients showed a small increase in free [Mg(2+)] while in PFK patients the pattern of free [Mg(2+)] was related to the rate of PME recovery. CONCLUSION: i) homeostasis of free [Mg(2+)] in human skeletal muscle is strongly linked to pH as shown by patients' [Mg(2+)] pattern during exercise; ii) the pattern of [Mg(2+)] during exercise and post-exercise recovery in both PFK patients suggests that [Mg(2+)] is influenced by the accumulation of the phosphorylated monosaccharide intermediates of glycogenolysis, as shown by the increased PME peak signal. iii) (31)P MRS is a suitable tool for the in vivo assessment of free cytosolic [Mg(2+)] in human skeletal muscle in different metabolic conditions

Intracellular magnesium content changes during mitochondria-mediated apoptosis: in depth study of early events on mitochondrial membrane potential

A recent study showed the antitumor activity of a new indole-derivative &ndash; MM-67 &ndash; inducing mitochondria-mediated apoptosis and a decrease of intracellular magnesium (Mg) concentration in HT29 colon cancer cells. Aim of this work was to assess cellular Mg levels throughout MM-67-induced apoptosis from the early to the final stage of the process and to evaluate the correlation with mitochondrial membrane potential (&Delta;&Psi;m) variations. All analysis were performed by flow cytometry: &Delta;&Psi;m was assessed by using mitochondrial potential sensitive dye DiOC6, while free and total intracellular cation concentrations were assessed by using the commercial probe MagFluo4-AM (Kd=4.7 mM), and the new synthesized DCHQ5 (Kd=8.3 mM), respectively. Our results evidenced that the MM67 induced apoptosis is characterized by a direct correlation between &Delta;&Psi; and free intracellular Mg content variations

Imbalance of Mg Homeostasis as a Potential Biomarker in Colon Cancer

Background: Increasing evidences support a correlation between magnesium (Mg) homeostasis and colorectal cancer (CRC). Nevertheless, the role of Mg and its transporters as diagnostic markers in CRC is still a matter of debate. In this study we combined X-ray Fluorescence Microscopy and databases information to investigate the possible correlation between Mg imbalance and CRC. Methods: CRC tissue samples and their non-tumoural counterpart from four patients were collected and analysed for total Mg level and distribution by X-Ray Fluorescence Microscopy. We also reviewed the scientific literature and the main tissue expression databases to collect data on Mg transporters expression in CRC. Results: We found a significantly higher content of total Mg in CRC samples when compared to non-tumoural tissues. Mg distribution was also impaired in CRC. Conversely, we evidenced an uncertain correlation between Mg transporters expression and colon malignancies. Discussion: Although further studies are necessary to determine the correlation between different cancer types and stages, this is the first report proposing the measurement of Mg tissue localisation as a marker in CRC. This study represents thus a proof-of-concept that paves the way for the design of a larger prospective investigation of Mg in CRC

Anterior cutaneous nerve block for analgesia in anterior chest trauma: is the parasternal approach necessary?

In recent years, several techniques of regional anesthesia have been proposed to provide analgesia to the anterior thoracic cage; notably, most of these techniques require a parasternal approach. However, in this context, the potential role of a more common and well-established technique, namely the modified pectoral nerve block (known as PECS II block), has been poorly investigated. Here, we describe a case involving a patient with bilateral anterolateral multiple rib fractures associated with sternum fracture, who was successfully treated using bilateral PECS II blocks. Our experience indicates that the PECS II block can provide excellent analgesia in cases involving anterior rib and sternum fractures. Because it is easier to perform and may be safer than other parasternal techniques, the PECS II block should be considered when providing analgesia for traumatic injuries of the anterior thorax