A formula has been deduced, and named as 2ESKV, relating the concentration of two consecutive substrates of a metabolic cycle with the kinetic constants of the two enzymes involved in their synthesis and degradation. ...A formula has been deduced, and named as 2ESKV, relating the concentration of two consecutive substrates of a metabolic cycle with the kinetic constants of the two enzymes involved in their synthesis and degradation. After application of formula 2ESKV to consecutive pairs of substrates and enzymes, a system of interrelated equations was obtained allowing a great variety of theoretical postulates to calculate, back and forth: bunches of unknown enzyme kinetic constants and substrate concentrations, from complementary sets of known data. This vision of a metabolic cycle is of partial application to irreversible pathways and can be useful for modeling and understanding of metabolomics data. To our knowledge, the formula 2ESKV is here described for the first time.展开更多
A system of differential equations has been used to simulate a model metabolic cycle, containing only one initial substrate and 8 irreversible enzymes. The metabolic course of the intermediates (products/substrates) w...A system of differential equations has been used to simulate a model metabolic cycle, containing only one initial substrate and 8 irreversible enzymes. The metabolic course of the intermediates (products/substrates) was also explored in different situations: changes in the kinetic constants of one of the enzymes of the cycle;introduction of one reversible step;consecutive increments in the Km values of each enzyme of the cycle and the presence of two initial substrates. A decrease or an increase in the Km value of one of the enzymes of the cycle promotes a decrease or an increase in the steady state level of its own substrate, respectively;by the contrary, a decrease or an increase in the Vmax value promotes, respectively, an increase or a decrease in the stationary level of the corresponding substrate. A comparison between a linear and a cyclic metabolic pathway is also presented.展开更多
A metabolic cycle can be viewed as a central core and its branches. The central core is here firstly considered as a pre-closed metabolic cycle (CMC), with a unique first substrate, but with no input or output of othe...A metabolic cycle can be viewed as a central core and its branches. The central core is here firstly considered as a pre-closed metabolic cycle (CMC), with a unique first substrate, but with no input or output of other components. By contrast, the metabolic cycles in nature are open metabolic cycles (OMC) with output and input of external substrates (through “metabolic branches”), modulating continuously the enzyme activities and the total concentration of their substrates thorough complex regulatory phenomena. In this work, the transition from a Closed to an Open metabolic cycle has been simulated by a consecutive entry and exit of two components through the catalytic action of two enzymes. It is known that after any alteration of the initial conditions, the cycles need a time to reach new equilibrium. We have measured the changes of transition time (T.T.) values in 81 models of CMC differing in Km or Vmax values. In general, the T.T. tends to be shorter in cycles with preponderant lower Km and higher Vmax values. Further, Mathematica refinement for the estimation of transition time from the data previously calculated can be obtained with the use of the command Interpolating Function.展开更多
The metabolic cycle firstly considered here is composed of a unique initial substrate, six enzymes, and five empty boxes to accommodate the substrates derived from the transformation of the initial substrate. This cyc...The metabolic cycle firstly considered here is composed of a unique initial substrate, six enzymes, and five empty boxes to accommodate the substrates derived from the transformation of the initial substrate. This cycle was considered as a pre-Closed Metabolic Cycle (CMC). Using this model, the influence of changing the kinetic constant values of any enzyme on the substrate concentration was explored. This model was transformed into an open metabolic cycle (OMC) by the input and output of two metabolites catalyzed by two external enzymes. In this case, the relative rates of input and output of metabolites were also examined;it can be concluded that the OMC cycles form delicate and fragile structures which can be theoretically disrupted, making them metabolically unfeasible.展开更多
文摘A formula has been deduced, and named as 2ESKV, relating the concentration of two consecutive substrates of a metabolic cycle with the kinetic constants of the two enzymes involved in their synthesis and degradation. After application of formula 2ESKV to consecutive pairs of substrates and enzymes, a system of interrelated equations was obtained allowing a great variety of theoretical postulates to calculate, back and forth: bunches of unknown enzyme kinetic constants and substrate concentrations, from complementary sets of known data. This vision of a metabolic cycle is of partial application to irreversible pathways and can be useful for modeling and understanding of metabolomics data. To our knowledge, the formula 2ESKV is here described for the first time.
文摘A system of differential equations has been used to simulate a model metabolic cycle, containing only one initial substrate and 8 irreversible enzymes. The metabolic course of the intermediates (products/substrates) was also explored in different situations: changes in the kinetic constants of one of the enzymes of the cycle;introduction of one reversible step;consecutive increments in the Km values of each enzyme of the cycle and the presence of two initial substrates. A decrease or an increase in the Km value of one of the enzymes of the cycle promotes a decrease or an increase in the steady state level of its own substrate, respectively;by the contrary, a decrease or an increase in the Vmax value promotes, respectively, an increase or a decrease in the stationary level of the corresponding substrate. A comparison between a linear and a cyclic metabolic pathway is also presented.
文摘A metabolic cycle can be viewed as a central core and its branches. The central core is here firstly considered as a pre-closed metabolic cycle (CMC), with a unique first substrate, but with no input or output of other components. By contrast, the metabolic cycles in nature are open metabolic cycles (OMC) with output and input of external substrates (through “metabolic branches”), modulating continuously the enzyme activities and the total concentration of their substrates thorough complex regulatory phenomena. In this work, the transition from a Closed to an Open metabolic cycle has been simulated by a consecutive entry and exit of two components through the catalytic action of two enzymes. It is known that after any alteration of the initial conditions, the cycles need a time to reach new equilibrium. We have measured the changes of transition time (T.T.) values in 81 models of CMC differing in Km or Vmax values. In general, the T.T. tends to be shorter in cycles with preponderant lower Km and higher Vmax values. Further, Mathematica refinement for the estimation of transition time from the data previously calculated can be obtained with the use of the command Interpolating Function.
文摘The metabolic cycle firstly considered here is composed of a unique initial substrate, six enzymes, and five empty boxes to accommodate the substrates derived from the transformation of the initial substrate. This cycle was considered as a pre-Closed Metabolic Cycle (CMC). Using this model, the influence of changing the kinetic constant values of any enzyme on the substrate concentration was explored. This model was transformed into an open metabolic cycle (OMC) by the input and output of two metabolites catalyzed by two external enzymes. In this case, the relative rates of input and output of metabolites were also examined;it can be concluded that the OMC cycles form delicate and fragile structures which can be theoretically disrupted, making them metabolically unfeasible.
