Kinetic simulation of malate-aspartate and citrate-pyruvate shuttles in association with Krebs cycle

Abstract

In the present work, we have kinetically simulated two mitochondrial shuttles, malate-aspartate shuttle (used for transferring reducing equivalents) and citrate-pyruvate shuttle (used for transferring carbon skeletons). However, the functions of these shuttles are not limited to the points mentioned above, and they can be used in different arrangements to meet different cellular requirements. Both the shuttles are intricately associated with Krebs cycle through the metabolites involved. The study of this system of shuttles and Krebs cycle explores the response of the system in different metabolic environments. Here, we have simulated these subsets individually and then combined them to study the interactions among them and to bring out the dynamics of these pathways in focus. Four antiports and a pyruvate pump were modelled along with the metabolic reactions on both sides of the inner mitochondrial membrane. Michaelis-Menten approach was extended for deriving rate equations of every component of the system. Kinetic simulation was carried out using ordinary differential equation solver in GNU Octave. It was observed that all the components attained steady state, sooner or later, depending on the system conditions. Progress curves and phase plots were plotted to understand the steady state behaviour of the metabolites involved. A comparative analysis between experimental and simulated data show fair agreement thus validating the usefulness and applicability of the model.

A Simple Dynamic Model for Mitochondrial Metabolism

“…Reactions of the CAC are described with eight differential equations with Michaelis-Menten reaction kinetic. Korla et al (2015) extends the earlier model with two transporter systems.…”

The scale-free nature of protein sequence space

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Features of the Hemostasis and Platelets Enzyme Activity in Patients with Different Sensitivity to Acetylsalicylic Acid by the Acute Coronary Syndrome

“…Состояние аэробного дыхания зависит не только от интенсивно-сти субстратного потока по циклу Кребса, но и опре-деляется уровнем водородного градиента в мито-хондриях, который, в свою очередь, поддерживается малат-аспартатным шунтом. Ключевую реакцию малат-аспартатного шунта катализирует НАДН-МДГ [16,17]. У чАСК и рАСК пациентов активность НАДН-МДГ в тром-боцитах снижена как в 1-е сут, так и на 10-е сут лече-ния.…”