THIS IS TOTALLY RADICAL!
In this paper she basically calls the accepted control of NO by hydroxycbl to be the starvation workaround for lacking adenosylb12.
Hypotheses in the Life Sciences Volume 2 Issue 2 pp 31-54
The Very Large Gorilla Sitting in the Room? Adenosylcobalamin is the Missing Link: its Radical and Tetrahydrobiopterin are the Principal in vivo Catalysts for Mammalian Nitric Oxide Synthases.
Carmen Wheatley
Orthomolecular Oncology, (registered charity no. 1078066), 4 Richmond Road, Oxford, OX1 2JJ, and St Catherine’s College, Oxford, OX1 3UJ, UK.
Abstract
Mammalian nitric oxide synthases (NOS) are a source of the universal second messenger, and pivotal biochemical molecule, nitric oxide (.NO). NOS are assumed to function catalytically in a haem-centred manner, by analogy with cytochrome P450. Yet, they differ significantly. Cobalamin, vitamin B12, is believed to function almost solely as an .NO scavenger and, latterly, as a direct, physiological inhibitor of the NOS. Yet, in pathology, associated to cobalamin deficiency, functional or otherwise, NOS over-produce superoxide, peroxynitrite (ONOO-), and other reactive nitrite species, rather than .NO (Figure 7). This paper offers a radical, new solution to the gaps and inconsistencies in the current understanding of the mechanism of haem-centred NOS catalysis, which also challenges the other existing paradigm of cobalamin as just an .NO mop. Examination of a wide diversity of NOS and cobalamin-dependent enzyme structure-function studies, as well as data from the .NO/cobalamin chemical, biochemical, immunological, genetic, and clinical literature, offers indications that cobalamin, specifically, in one of its active forms, adenosylcobalamin (AdoCbl), may have a third, eukaryotic coenzyme function as the principal cofactor of well-regulated NOS catalysis in vivo. The AdoCbl-centred NOS reaction is described in detail (Figure 5), and some existing evidence that, in vitro, without AdoCbl, NOS turnover activity is significantly slower than in in vivo AdoCbl-rich environments, is presented. AdoCbl, in conjunction with tetrahydrobiopterin, couples NOS oxygen binding/activation to L-arginine hydroxylation and .NO synthesis much more effectively than does haem, overcoming NOS spatial and redox problems, leading to productive catalysis, decreased radical formation/escape, with a consequent increased ratio of .NO to ONOO-, and prevention of pathology (Figures 5 & 7). In vivo, haem-centred NOS catalysis may, in fact, be the back-up NOS reaction, and it‟s predominance in the absence of AdoCbl, with a consequent lowering of the .NO/ONOO- ratio, is the real source of supposedly .NO derived pathology.
You have to read the paper to find the Boron reference. Its in there somewhere in 25 pages. I found it the first time through but not again. This is her 4th paper on cobalamins and inflammation, the first three were the "Scarlet Pimpernel" papers. Again, this is a speculative paper advancing the edge of scientific understanding.
DISCLAIMER
I am a self taught systems analyst and consultant. I am not credentialed, certified or licensed to do anything besides drive a car. I have been disabled by the disease processes being discussed and affecting neurology in a multitude of ways for 10 years and impaired in a variety of ways and levels for 54 years before that. Everything I say is my opinion, synthesis, understanding or otherwise of my own creation except direct attributed quotes. Approximate paraphrases are also my interpretation of what I have read. All of this is at best my data analysis, understanding, synthesis and hypotheses and not to be construed as medical advice. I am not responsible for anything you do with any information provided in any way. Anything you do is your own responsibility and at your own risk. There are no published peer reviewed studies backing up my opinions or statements, except the incidental ones quoted or implicit in my synthesis or understanding, and then only in so far any reading of such papers may confer. Your interpretations, actions and variations of what I say are strictly at your own risk.
