Fluoride inhibits cell membrane pumps (and all other proteins)

[www.jbc.org]

The Journal of Biological Chemistry 1992
American Society for Biochemistry and Molecular Biology.

Inhibition of the Na,K-ATPase by Fluoride
Parallels with Its Inhibition of The Sarcoplasmic Reticulum Ca-ATPase
Alexander J. Murphy and J. Craig Hoover
Department of Biochemistry, School of Dentistry, University of the Pacific, San Francisco, California.

[excerpt:]

As a primary means by which cation gradients across the plasma membrane are produced, the Na,K-ATPase [Na/K pump] plays a central role in a number of cell functions, including maintenance of the electrochemical membrane potential. Among the many challenges this enzyme presents is elucidating the molecular mechanism by which ATP hydrolysis is coupled to ion translocation. An important aspect of this is understanding the structural changes produced by the binding of transported ions, substrates, products, and effectors. Inhibitors can be useful in this pursuit because they may reveal the nature of ligand-enzyme interactions or stabilize interesting but elusive intermediates, thereby leading to refinement of the molecular mechanism. Among those that have been extensively utilized in Na,K-ATPase studies are ouabain. In a recent study of the effect of fluoride on the Ca-ATPase [Ca pump] of SR [sarcoplasmic reticulum], we found that this anion is a slow, tight-binding inhibitor, appearing to interact in concert with magnesium at the phosphorylation site. Since the Na,K-ATPase has many structural and mechanistic features in common with the calcium pump, comparison of the effect of fluoride suggested itself. In addition, a report showing the inhibitory effect of fluoride complexes of aluminum and beryllium on the Na,K-ATPase raised the question of whether at least some of the inhibition was due to fluoride itself. Earlier studies of the inhibitory effect of fluoride on the Na,K-ATPase did not sort out possible effects due to endogenous aluminum. In this report, we describe results of kinetic measurements of the interaction of fluoride and the Na,K-ATPase, using deferoxamine to remove the effect of endogenous aluminum. The results indicate that fluoride itself is inhibitory and that most features of the interaction are quite similar to fluoride’s inhibition of the SR Ca-ATPase.


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Note:

-- fluoride inhibits membrane pumps by undoing the 'hydrogen bonds' that maintain their complex protein structural-functional conformation (configuration). For structure pictures of Na/K and Ca pumps see [www.pdb.org]

-- all body proteins are functionally degraded by fluoride: - membrane pumps, electrolyte channels, collagen, fibrinogen, fibrin, many/ most hormones (eg ANP and BNP), nerve cell proteins, etc etc.

-- Hydrogen Bonds in Proteins: Role and Strength [www.els.net]
Hydrogen bonds provide most of the directional interactions that underpin protein folding, protein structure and molecular recognition. The core of most protein structures is composed of secondary structures such as α helix and β sheet. This satisfies the hydrogen-bonding potential between main chain carbonyl oxygen and amide nitrogen buried in the hydrophobic core of the protein. Hydrogen bonding between a protein and its ligands (protein, nucleic acid, substrate, effector or inhibitor) provides a directionality and specificity of interaction that is a fundamental aspect of molecular recognition. The energetics and kinetics of hydrogen bonding therefore need to be optimal to allow the rapid sampling and kinetics of folding, conferring stability to the protein structure and providing the specificity required for selective macromolecular interactions.



Edited 1 time(s). Last edit at 01/04/2013 02:41PM by Erling.

From the City of Portland website:

Number 3 is very interesting "Portland would be the last major city in the United States to add fluoride to the public drinking water."

Better late than never-

[www.portlandoregon.gov]


Fluoride Information
Frequently Asked Questions

Proposed Fluoridation of the City of Portland’s Drinking Water Supply
Updated November 30, 2012

1. Will the City of Portland add fluoride to its drinking water?

The decision to add fluoride to Portland’s drinking water will be determined by a public vote. On December 20, 2012, the City Council voted to approve a resolution that moves that public vote to the May, 21, 2013 Special Election.

On September 19, 2012, the Portland City Council unanimously passed an Ordinance that authorized and directed the Portland Water Bureau to add fluoride to the drinking water supply. This Ordinance will not be immediately enacted upon due to a citizen petition drive that garnered enough voter signatures to call for a public vote. All work by the Water Bureau to plan, design and construct a fluoride delivery facility was stopped once voter signatures were validated.

2. Why did the City of Portland consider adding fluoride to drinking water at this time?
A citizens group (Upstream Public Health) approached Commissioner Randy Leonard to ask him to sponsor a fluoridation measure to combat what the group called a rising problem of tooth decay in many children in Portland, especially for low-income and minority families. Commissioner Leonard and Commissioner Nick Fish concluded that the qualified science and facts about the health promotion effects of fluoride, even for adults, were sufficient reasons to call for a Council vote to add fluoride to the drinking water.

3. Are there any other large cities in the United States that do not add fluoride to their drinking water at this time?
Portland would be the last major city in the United States to add fluoride to the public drinking water.

4. Would the water that Portland provides to other cities and water districts also be fluoridated?
Yes. Since the potential fluoridation facility would be located near the Bull Run water source, wholesale customers would receive fluoridated water.

5. Where can I get information about the health effects of fluoridated water?
The Center for Disease Control website has a great deal of information about the subject of Community Water Fluoridation.

6. Does fluoride change the taste of drinking water?
No. No one should be able to taste the difference if fluoride is added to the water. Also, there is no smell to fluoridated drinking water.

7. Does the Oregon Health Authority or Multnomah County Health Department have a position on drinking water fluoridation?

Both the Oregon Health Authority (OHA) and Multnomah County Health Department support the fluoridation of the City of Portland drinking water. It was stated in the Ordinance that the OHA recommended fluoridation. The US Department of Health and Human Services further promotes the benefits of fluoride.

8. What are the costs of adding fluoride – how much would an average customer have to pay if fluoride is added to the drinking water?
The current estimate to design and construct a fluoride delivery facility is estimated at $5 million. The cost to operate and maintain the facility is estimated $500,000 per year. The cost would be about 25 cents per month per household.

9. Are there any federal grants or other sources of revenue to help defray the costs of adding fluoride to the drinking water?

No. The cost to build and operate the facility will be paid through rates charged to our retail and wholesale customers.

10. Would fluoride be added to both the Bull Run and Groundwater supplies?

It is assumed that fluoridation of groundwater from the South Shore Columbia Well Field would not be required since it is not used on a regular basis. As Portland’s supplemental water source, groundwater is blended with Bull Run water at the city’s reservoir at Powell Butte, the hub of the Portland’s water system.

In the rare event where the Bull Run supply is required to be shut down, groundwater is used as the city’s sole source of water. The short-term nature of such an event is such that building a separate fluoridation system for the groundwater supply is not cost-effective.

11. Are there filters available that I can use in my house to remove the fluoride, if voters approve to add it to the water supply?

Activated Alumina Defluoridation filters are available for home use but are relatively expensive($30/filter) and require frequent replacement. Distillation Filtration Systems are also commercially available for purchase to remove fluoride from water.

12. What type of fluoride would be used?
Fluoride will be fed into the water system at a 23 percent solution of fluorosilicic acid. Fluorosilicic acid is commercially available as a 20 to 35% solution. The most common concentration used in water treatment applications is 23 percent.

13. What is the standard recommended concentration of fluoride for municipal water supplies?

This is the concentration recommended by the national Centers for Disease Control (CDC) is 0.7 milligrams per liter.