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Y Schiffmann

Publications and source records attributed to Y Schiffmann.

16 recordsLinked to original sources
PubMed1991

An hypothesis: phosphorylation fields as the source of positional information and cell differentiation--(cAMP, ATP) as the universal morphogenetic Turing couple.

It is hypothesized that (cAMP, ATP) is the elusive, universal Turing morphogenetic couple, which defies the second law of thermodynamics, i.e. the inexorable march towards homogeneity. cAMP and ATP can be distributed nonhomogeneously because the whole of the intermediary metabolism is so organized that they mutually satisfy the Turing bifurcation conditions upon nonlocalized application of an extracellular ligand, in particular a soluble peptide growth factor, which is nature's distinguished universal bifurcation parameter, acting homogeneously in space and removing the substrate inhibition from adenylate cyclase and thus triggering embryonic induction by triggering the (cAMP, ATP) Turing system. The hypothesis predicts that although the extracellular signal, the growth factor, is applied homogeneously, an organized "dissipative structure" will emerge spontaneously in the responding tissue; this "symmetry breaking" in a reaction-diffusion system occurs precisely in the manner envisaged by Turing, where (cAMP, ATP) constitutes the "reaction-diffusion system". This Turing bifurcation explicates the recent experiments where a differentiated embryoid emerges from the mere immersion of frog animal caps in an homogeneous growth factor solution, and similar experiments on chicks. The "metabolic" patterns found by Child and colleagues also reflect dissipative structures arising in a (cAMP, ATP) reaction-diffusion system when interpreted in the light of modern biochemistry: in particular, the localized glycogen depletion reflects localized cAMP; localized redox, respiratory or susceptibility activity reflects localized ATP. The dramatic collapse of organized structure found by Child and colleagues, for example, when Planaria or a section of it is exposed to an homogeneous environment of a narcotic solution, and the reemergence of structure upon return to water, are explained on the basis of the violation or satisfaction of the Turing bifurcation conditions with respect to (cAMP, ATP), respectively. cAMP is the "activator", ATP is the "inhibitor", and together they mutually satisfy the four activator-inhibitor inequalities, including the all-important autocatalytic cAMP production, as well as the lateral inhibition condition. The functional significance of gap junctions is to generate a multicellular purely reaction-diffusion system for (cAMP, ATP) as envisaged by Turing. It is emphasized that localization and pattern formation occur intracellularly in gap junction-coupled cells and not, as often suggested, extracellularly, the latter localization being too fragile to be maintained for long enough, and soon succumbing to the mixing effect of convection and movement. The activator-inhibitor property of (cAMP, ATP) means that the spatial distribution of cAMP and ATP could be not only nonhomogeneous but also of the same shape.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1989

The second messenger system as the morphogenetic field.

For sixty years morphogenetic fields have been assumed. We suggest a realization for such a field: the second messenger (in particular cyclic AMP) and its substrate (in particular ATP) are suggested to be the activator-morphogen and inhibitor respectively. Gene transcription is derived as an hysteretic function of the second messenger (cyclic AMP).

Adenosine Triphosphate↗
PubMed1989

Bistability and control for ATP synthase and adenylate cyclase is obtained by the removal of substrate inhibition.

The thesis of this article is that the raison d'être of the electron transfer chain and the receptor system is to remove 'substrate inhibition' of the enzymes ATP synthase and adenylate cyclase respectively. Activation by energization or hormone is analogous and presents the features of ideal control system; bistability, hysteresis, sensitivity and amplification, and rapid transitions between resting and active states. In the first part of the article, the simplest nontrivial model conforming with the experimental results is put forward. After the system is described, nonlinear and linear models are developed. An important aspect captured by the model is that the enzyme is structurally asymmetric corresponding to the assumption of regulatory site(s) distinct from catalytic site(s). The structural distinction between a regulatory site and a catalytic site entails different binding and specificity properties of the two types of sites with respect to the nucleotides. In the second part, the experimental evidence for the theory is discussed. It is shown that energization and hormone indeed reduce 'substrate inhibition' and that the properties of time lag and criticality predicted by the theory are indeed verified in experiment and are in turn explained by the theory. The theory can explain and correlate various hitherto unexplained experimental phenomena such as the irreversibility of ATP synthesis and the functional role of the ATP synthase asymmetry. The property of hysteresis predicted by the nonlinear model, is indicated by postillumination ATP synthesis, and preactivation of chloroplasts with reduced dithiols indeed display 'hysteresis loops'. In Aplysia memory for short term sensitization may reside in the hysteretic prolonged elevation of cAMP in sensory neurons.

ATP Synthetase Complexes↗
PubMed1982

Biological fluid membrane generates triggering cycle and homeostasis.

A working engine has to operate in cycles, and at completion of a work cycle it should revert to its initial state. The ubiquitous unit cycle in medicine and physiology is characterized by a rapid upstroke followed by a plateau, which is in turn followed by a quick restoration to a resting state. So far, such cycles could not be derived from the basic laws of chemistry, in particular from the law of mass action; but within the context of a new biochemical control theory, which replaces the notion of conformational change by redistribution in the membrane, such a cycle can be derived from the law of mass action if the system is two dimensional, namely if the biochemical reactions are restricted to an optimally fluid membrane which is an open nonequilibrium system. The failure of this universal mechanism for triggering cycle is suggested to be a universal cause of disease. This failure involves abnormal membrane fluidity and leakage of enzyme and receptor from the membrane.

Action Potentials↗