The tipping point (revisited): G6PD

Glucose-6-phosphate dehydrogenase is indispensable in embryonic development by modulation of epithelial-mesenchymal transition via the NOX/Smad3/miR-200b axis (1/9/18)

Excerpt:

The proposed mechanism concerning G6PD and the embryonic development of zebrafish (Fig. 1) is largely based on the novel findings of the current study, particularly that G6PD knockdown modulates the EMT process.

Conclusion:

Taken together, these data strongly suggest that in embryonic development, G6PD plays an essential role as an integral component of the NOX/Smad3/miR-200b axis.

The essential role that G6PD plays is included in the context of how the light-activated assembly of the microRNA-RNA-peptide nanocomplex was linked to the creation of Glucose-6-phosphate dehydrogenase (G6PD). The energy-dependent fixation of RNA-mediated amino acid substitutions has been linked from the physiology of pheromone-controlled reproduction in species from microbes to humans via conserved molecular mechanisms and feedback loops. Thus, G6PD establishes the connection from the creation of an enzyme to the feedback loops.

See for example:  Feedback loops link odor and pheromone signaling with reproduction (2005)

All serious scientists convinced that enzymes do not create themselves. They also know that random mutations cannot be linked from fixation of amino acid substitutions to the stability of organized genomes in all living genera.

But see: An appeal to magic? The discovery of a non-enzymatic metabolism and its role in the origins of life (8/29/18)

By serving as a ‘template’ in the Darwinian selection processes, the existence of non-enzymatic metabolism-like reaction sequences may have allowed life to overcome the end-product problem and facilitated the origin of metabolic pathways. Furthermore, there is growing evidence that enzymes might have exploited amino acid-based as well as metal ion catalysis since the beginnings of metabolism. Hence, the origin of life, often dismissed as a ‘philosophical problem’, is increasingly becoming a problem that is experimentally tangible.

The magic of philosophical problems has been removed from consideration by experimental evidence that details the fact that top-down causation is energy-dependent and biophysically constrained.

See: Do sulfate radicals really enable a non-enzymatic Krebs cycle precursor? (1/29/19)

The problem is that ferrous ions and the persulfate are not regenerated during the course of reaction, which means they cannot be described as catalysts.

The connection from the RNA world to gene-centric theories about the automagical emergence of energy and evolution was eliminated in the context of: RNA-catalysed synthesis of complementary-strand RNA (1989), which has been linked to the horrid failure of the CRISPR Cas9 gene editing technology, which causes too many mutations to be considered in the context of light-activated carbon fixation and biophysically constrained RNA interference.

Immediately, the magic was allowed to re-enter the discussion.

See: Reply to ‘Do sulfate radicals really enable a non-enzymatic Krebs cycle precursor?’ (1/29/19)

They claimed that Sutherland and Ritson were confused by what’s known about to all intelligent serious scientists about the light-activated fixation of carbon, which is the basis of all organic chemistry (single-reaction) yield values. They suggested that everything known  should be placed back into the context  of carbon recoveries in entire reaction networks. The intent to obfuscate cause and effect and place it back into the context of Big Bang cosmology and the emergence of energy is clear. The ask that the transient nature of light-activated carbon fixation be quantified via the a mathematical model and sum of all metabolites present at a given point in time across the entire system.

Simply put, the authors claim that Sutherland & Ritson included an incomplete experimental design, which caused analytical mistakes to emerge from the lack of essential controls. Indeed, it is unlikely that anyone will ever design a experiment that could successfully eliminate all the variables linked to the sum of all energy-dependent metabolites present at a given point in time across the entire system.

Rarely do you hear a claim about analytical mistakes that can be linked from Ralser’s appeal to magic to the pseudoscientific nonsense about the emergence of energy and light-activated carbon fixation, but here it is:

…the determination of reaction rates from data that do not meet the required statistical criteria, and cherry-picking instead of systematic sampling — caused their approach to fail.

See also: Magic traits in speciation: ‘magic’ but not rare? (2011)

…magic traits can be produced by a variety of mechanisms, including ones in which reproductive isolation arises as an automatic by-product of adaptive divergence.

Genetic dissection of assortative mating behavior (2019)

Ecologically relevant mating cues (sometimes known as “magic traits” [2,6]) are now predicted to be widespread in nature [6,7], and the last few years have seen considerable progress in our understanding of their genetic basis.

Researchers recently rediscovered a nutrient-dependent epigenetic variant that links vitamin C to what is probably a glucose and glucose dehydrogenase-dependent base pair change. The base pair change results in addition of a methyl group to a cytosine base, which takes on a hydroxyl group to form different 5-hydroxymethylcytosines (5hmCs). Different 5hmCs are associated with differences in cell types that have the same genetic backgrounds. Nutrient-dependent epigenetically-marked bases help to explain how hundreds of cell types in the human body and in the brain [24] are differentiated and how they maintain their glucose-dependent and other nutrient-dependent receptor-mediated identities [25].

  1. Kriaucionis, S.; Heintz, N., The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain. Science 2009, 324 (5929), 929-930. doi: 10.1126/science.1169786
  2. Wu, H.; Wang, C.; Gregory, K. J.; Han, G. W.; Cho, H. P.; Xia, Y.; Niswender, C. M.; Katritch, V.; Meiler, J.; Cherezov, V., et al., Structure of a Class C GPCR Metabotropic Glutamate Receptor 1 Bound to an Allosteric Modulator. Science 2014, Published Online March 6 2014. doi: 10.1126/science.1249489

Published as: Nutrient-dependent Pheromone-Controlled Ecological Adaptations: From Angstroms to Ecosystems (4/18/18)

Nutrient-dependent epigenetic effects on histone modifications and DNA methylation play an important role in stabilizing cell type identity and in orchestrating many developmental processes. For example, vitamin C appears to stimulate histone demethylases, which appear to alter the de novo creation of functional G protein-coupled genes such as olfactory receptor genes [15-19].

Researchers recently rediscovered a nutrient-dependent epigenetic variant that links vitamin C to what is probably a glucose and glucose dehydrogenase-dependent base pair change. The base pair change results in addition of a methyl group to a cytosine base, which takes on a hydroxyl group to form different 5-hydroxymethylcytosines (5hmCs). Different 5hmCs are associated with differences in cell types that have the same genetic backgrounds. Nutrient-dependent epigenetically-marked bases help to explain how hundreds of cell types in the human body and in the brain [20] are differentiated and how they maintain their glucose-dependent and other nutrient-dependent receptor-mediated identities [21].

When Marcus Ralser learned that his statistical manipulations of ‘magic’ were not acceptable to those who had linked the energy required for plant growth from sunlight to vitamin C via a glucose dehydrogenase-dependent base pair change, he blocked me from seeing his tweets @ralserlab.

For comparison, when Jon Entine learned that I was about to make him another example of human idiocy among so-called science journalists,  at he asked:

‘Are we all going to die?’ Entomologist breaks down the ‘bee-pocalypse’ that ‘threatens the global food supply’

 

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Author: James Kohl

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