Freddd
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This is all about inflammation, NOT methylation. In this paper Dr Wheatly (an oncologist) explains why AdoCbl (adb12, adob12, cobalamide, adenosylcobalamin, adenosylb12 etc) is "radically" more effective and completely different from the NO control of hydroxycbl. She suggests that this older view is the workaround for essentially AdoCbl starvation and is a faulty and incomplete view. This is a specualtive paper that basically lays the biochemical foundation for the active b12 protocol. I wish Rich was to see this and where his theories have lead. Methylation was one shoe, this is the gorilla's second shoe to drop. I am anxious to read the next few papers.
In this paper, availalble at Researchgate, the necessity of boron, as in the Anobol Dibencoplex adb12 also is shown. Also, where zinc fits in and of course Tetrahydrobiopterin.
This is revolutionary.
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,
There are many names for these active b12 vitamins. Adenosylcoblamin, adenosylb12, adenosylcbl, cobalamide, cobamamide, adocbl, adob12, adb12, adcbl, methylcobalamin, methylb12, methylcbl, mecocbl, mecbl, mb12, mecob12 and other similar ones.
In this paper, availalble at Researchgate, the necessity of boron, as in the Anobol Dibencoplex adb12 also is shown. Also, where zinc fits in and of course Tetrahydrobiopterin.
This is revolutionary.
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,
There are many names for these active b12 vitamins. Adenosylcoblamin, adenosylb12, adenosylcbl, cobalamide, cobamamide, adocbl, adob12, adb12, adcbl, methylcobalamin, methylb12, methylcbl, mecocbl, mecbl, mb12, mecob12 and other similar ones.
