Elements of the cellular metabolic structure

Abstract

A large number of studies have demonstrated the existence of metabolic covalent modifications in different molecular structures, which are able to store biochemical information that is not encoded by DNA. Some of these covalent mark patterns can be transmitted across generations (epigenetic changes). Recently, the emergence of Hopfield-like attractor dynamics has been observed in self-organized enzymatic networks, which have the capacity to store functional catalytic patterns that can be correctly recovered by specific input stimuli. Hopfield-like metabolic dynamics are stable and can be maintained as a long-term biochemical memory. In addition, specific molecular information can be transferred from the functional dynamics of the metabolic networks to the enzymatic activity involved in covalent post-translational modulation, so that determined functional memory can be embedded in multiple stable molecular marks. The metabolic dynamics governed by Hopfield-type attractors (functional processes), as well as the enzymatic covalent modifications of specific molecules (structural dynamic processes) seem to represent the two stages of the dynamical memory of cellular metabolism (metabolic memory). Epigenetic processes appear to be the structural manifestation of this cellular metabolic memory. Here, a new framework for molecular information storage in the cell is presented, which is characterized by two functionally and molecularly interrelated systems: a dynamic, flexible and adaptive system (metabolic memory) and an essentially conservative system (genetic memory). The molecular information of both systems seems to coordinate the physiological development of the whole cell.

Increased Lytic Efficiency of Bovine Macrophages Trained with Killed Mycobacteria

“…In summary, we present evidence that bovine macrophages can be “trained” to improve their lytic capacity, rather than just particle uptake, likely by epigenetic reprogramming [20, 21]. Our results are consistent with the concept of trained innate immunity recently proposed by Netea et al [1].…”

Long-term memory in the migration movements of enucleatedAmoeba proteus

“…From a molecular point of view, the amoebas' locomotion is controlled by complex metabolic networks, which operate as non-linear systems with dynamics far from equilibrium 16 . These biochemical networks involve an intricate interplay of multiple components of the cell migration machinery, including the actin cytoskeleton, ion channels, transporters, regulatory proteins such as the Arp2/3 complex or the ADF/cofilin family proteins 17,18 .…”

“…As a consequence of the efficient self-regulatory activity of the metabolic networks, each amoeba seems to be endowed with the ability to orientate its movement toward specific goals in the external environment, thereby developing efficient foraging strategies even in conditions of sparse resources when there is limited or no information as to where food is located. A large number of experimental studies on individual cells have demonstrated that important systemic behaviors are supported by astounding metabolic properties 16 . For instance, the single cellamoeboid Physarumpolycephalum can find the minimum-length solution between two points in a maze 19 , forming an optimized network closely approaching the purposely designed Tokyo railway system 20 to resolve complex multiobjective foraging problems 21 , and to learn and recall past events 22 .…”

“…For instance, the single cellamoeboid Physarumpolycephalum can find the minimum-length solution between two points in a maze 19 , forming an optimized network closely approaching the purposely designed Tokyo railway system 20 to resolve complex multiobjective foraging problems 21 , and to learn and recall past events 22 . These and other advances in the study of the cellular systemic metabolic properties 23,24 are bringing forth a new conceptual framework that defines the cell essentially as adynamic metabolic reactorin which most of the constituent biomolecules are synthesized and destroyed through cyclic biochemical reactions driven by enzymes.In turn, the enzymatic processes are integrated in functional networks that, on a global level, shape one of the most complex dynamic systems in nature 16 . As a consequence, millions of ions and molecules are continuously transformed with extreme precision through tightly regulated reactions, all of which are confined to a reduced space of microns.…”

Evidences of conditioned behavior in Amoeba Proteus

“…For instance, Hopfield-like attractor dynamics have been observed in self-organized enzymatic networks which have the capacity to store functional catalytic patterns that can be correctly recovered by specific input stimuli 8 . In addition, evidences of functional memory which can be embedded in multiple stable molecular marks during epigenetic processes have been reported 9 . On the other hand, long-term correlations (mimicking short-term memory in neuronal systems) have also been analyzed in experimental calcium-activated chloride fluxes belonging to Xenopus laevis oocytes 10 .…”