Talk:Hormesis: Difference between revisions

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imported>Howard C. Berkowitz
imported>Anthony.Sebastian
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::By receptor blocking, there actually are a number of places that the hormetic substance could work, such as being a presynaptic reuptake agonist or antagonist.
::By receptor blocking, there actually are a number of places that the hormetic substance could work, such as being a presynaptic reuptake agonist or antagonist.
:::Howard, very interesting, and I see your point.  I think discussing suggested mechanisms of hormesis should come soon in the developing article, as ideas about mechanism will make reader undestanding of the phenomenon a lot easier.  You have thought deeper on this than I have, but I will try to catch up.
:::Re Briggs-Haldane vs. Michaelis-Menten, I wrote the following in the article on [[J. B. S. Haldane]]. Not exactly my area of expertise, so feel free to correct:
:::Early on (1925), at Cambridge University, Haldane applied his early-acquired and life-long passion for mathematical analysis of biological chemistry to the field of enzymology.  Enzymologists study the behavior of [[Enzyme|enzymes]], the [[Protein|protein]] catalysts that accelerate biochemical reactions in living cells without themselves getting consumed in the reactions.  Among other studies, enzymologists generate schematic and mathematical models of the many different kinds of biochemical reactions catalyzed by enzymes.  With a colleague, George E. Briggs, Haldane presented a theoretical analysis of enzyme catalyzed reactions that could account for quantitative measurements of the rates of many of such reactions ('enzyme kinetics').  Briggs and Haldane used a different reaction equation and a more generally applicable assumption about the process of enzyme catalyzed reactions compared to the earlier model presented by Michaelis and Menten &mdash; specifically, they presented the mathematics of quasi-steady-state relationship of the enzyme-substrate complex whereas Michaelis and Menten analyzed the reactions at equilibrium.<ref name=briggs25>Briggs GE, Haldane JBS. (1925)  [http://www.biochemj.org/bj/search/asptemplate.asp?SearchForm=%25%25SearchForm%25%25&OrigSearchForm=D%3A%5Cbj%5Cbj%5Csearch%5Csearch.htm&cmd=search&searchType=bool&request=%28%28DCCreator+contains+Briggs%29+and+%28DCCreator+contains++haldane%29%29+and+%28DCDate+contains+1924-01-01%7E%7E1925-12-31%29+and+%28arttype+contains+bjabs%29&S=8&Search_ID=0&FTOnly=0&author=Briggs%2C+haldane&author_mode=and&title=&title_mode=or&abstract=&abstract_mode=or&request2=&full_mode=or&keywords=&keywords_mode=or&fmonth=&fyear=1924&tmonth=&tyear=1925&volume=&firstpage=&go=Search&sort=DCDate&maxFiles=25 A note on the kinetics of enzyme reactions.] ''Biochem J'' 19:338-339
:*They end the paper: “It may be remarked that with this modification of their [earlier] theory, Michaelis and Menten's analysis of the effects of the products of the reaction, or other substances which combine with the enzyme, still holds good.”</ref> The Briggs-Haldane analysis remains the standard approach to enzymatic reaction ‘kinetics’, and has set a foundation for, and stimulated, the further developments in that field up to the 21st century.<ref>Tzafriri AR, Edelman ER. (2004) [http://www.sciencedirect.com/science/article/B6WMD-4B3G244-4/2/d3f1b9304fde03b2cef31cdcb40857c0 The total quasi-steady-state approximation is valid for reversible enzyme kinetics.] ''Journal of Theoretical Biology'' 226 (3):303-313]</ref><ref>Pedersena MG, Bersani AM, and Bersani E. (2007) The total quasi-steady-state approximation for fully competitive enzyme reactions. Bull.Math.Biol. 69 (1):433-457 PMID 16850351</ref>
:::--[[User:Anthony.Sebastian|Anthony.Sebastian]] 01:27, 13 October 2008 (UTC)
<references/>


====Pathway up/downregulation====
====Pathway up/downregulation====
::A slightly different but not completely unrelated issue: could a hormetic dose of Z still be sufficient to activate or suppress an excretion pathway, such as one of the cytochrome P240 variants
::A slightly different but not completely unrelated issue: could a hormetic dose of Z still be sufficient to activate or suppress an excretion pathway, such as one of the cytochrome P240 variants
:::Good thinking.  Surely. --[[User:Anthony.Sebastian|Anthony.Sebastian]] 01:27, 13 October 2008 (UTC)

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 Definition:  A quantitative and qualitative dose-response relationship in which the effect at low concentrations occurs in the opposite direction from that expected from the effect observed at higher concentrations. [d] [e]
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Starting article on "hormesis"

Encouraging collaboration.

Hoping this is a reasonable approach

One of the first thing that hormesis brings to mind is type-0 and type-1 pharmacokinetics, especially drug (or toxin) clearance. Obviously simplified, zero-order kinetics has a basic model that the excretion process has infinite capacity, while first-order kinetics has a saturation point. More precisely, zero-order kinetics asssume a constant absolute rate of clearance, while first-order clearance assumes a constant fraction of the total body concentraion over time.

Such effects are at the high-end range of dose-effect mechanisms.

At a low end -- thinking of infection rather than drugs -- in biohazard mitigation and biological warfare work, there is a well-established "minimum infective concentration" (often expressed as the 50th percentile). Tularemia, for example, can establish disease with only a few cells, where more dangerous agents require a considerably larger concenntration.

Howard C. Berkowitz 12:32, 1 October 2008 (CDT)

Interesting, Howard. Will give this some thought, and check 'hormesis' references to see if anyone touches on the subject.--Anthony.Sebastian 16:51, 12 October 2008 (UTC)

Michaelis-Menten work relevant here?

Is this an area that should be in this discussion? Howard C. Berkowitz 13:08, 1 October 2008 (CDT)

Howard, how would you approach this? Would Briggs-Haldane kinetics serve better? Hope you will elaborate. --Anthony.Sebastian 16:51, 12 October 2008 (UTC)
I've worked less with Briggs-Haldane, but isn't there a significant range in which they both apply? [1]? Briggs-Haldane appears to be an extension. When talking about the general issues of hormesis, is the difference really significant, or could many hormetic effects be explained by competitive inhibition of enough receptors to block the present effect of some toxic substance at constant concentration? (see note below about another possible mechanism)
Let me answer directly, and also a little indirectly. Michaelis-Menten is about competitive inhibition. Assume chemical X is a toxin, even naturally produced. Further, there are cellular X-receptors, and there is a minimum trigger number of X-receptors that will cause an undesirable effect.
If chemical Y competes for X-receptors, and the quantity of X does not increase, the physiological effect of X is blocked. Receptor blocking (or interfering in the pathway that creates the substance for which the receptor is sensitized) is common to many effective drugs.
By receptor blocking, there actually are a number of places that the hormetic substance could work, such as being a presynaptic reuptake agonist or antagonist.
Howard, very interesting, and I see your point. I think discussing suggested mechanisms of hormesis should come soon in the developing article, as ideas about mechanism will make reader undestanding of the phenomenon a lot easier. You have thought deeper on this than I have, but I will try to catch up.
Re Briggs-Haldane vs. Michaelis-Menten, I wrote the following in the article on J. B. S. Haldane. Not exactly my area of expertise, so feel free to correct:
Early on (1925), at Cambridge University, Haldane applied his early-acquired and life-long passion for mathematical analysis of biological chemistry to the field of enzymology. Enzymologists study the behavior of enzymes, the protein catalysts that accelerate biochemical reactions in living cells without themselves getting consumed in the reactions. Among other studies, enzymologists generate schematic and mathematical models of the many different kinds of biochemical reactions catalyzed by enzymes. With a colleague, George E. Briggs, Haldane presented a theoretical analysis of enzyme catalyzed reactions that could account for quantitative measurements of the rates of many of such reactions ('enzyme kinetics'). Briggs and Haldane used a different reaction equation and a more generally applicable assumption about the process of enzyme catalyzed reactions compared to the earlier model presented by Michaelis and Menten — specifically, they presented the mathematics of quasi-steady-state relationship of the enzyme-substrate complex whereas Michaelis and Menten analyzed the reactions at equilibrium.[1] The Briggs-Haldane analysis remains the standard approach to enzymatic reaction ‘kinetics’, and has set a foundation for, and stimulated, the further developments in that field up to the 21st century.[2][3]
--Anthony.Sebastian 01:27, 13 October 2008 (UTC)
  1. ↑ Briggs GE, Haldane JBS. (1925) A note on the kinetics of enzyme reactions. Biochem J 19:338-339
    • They end the paper: “It may be remarked that with this modification of their [earlier] theory, Michaelis and Menten's analysis of the effects of the products of the reaction, or other substances which combine with the enzyme, still holds good.”
  2. ↑ Tzafriri AR, Edelman ER. (2004) The total quasi-steady-state approximation is valid for reversible enzyme kinetics. Journal of Theoretical Biology 226 (3):303-313]
  3. ↑ Pedersena MG, Bersani AM, and Bersani E. (2007) The total quasi-steady-state approximation for fully competitive enzyme reactions. Bull.Math.Biol. 69 (1):433-457 PMID 16850351

Pathway up/downregulation

A slightly different but not completely unrelated issue: could a hormetic dose of Z still be sufficient to activate or suppress an excretion pathway, such as one of the cytochrome P240 variants
Good thinking. Surely. --Anthony.Sebastian 01:27, 13 October 2008 (UTC)
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