Metals, Chelation and Enzymes - Not as confused

[Guest guest]

The following is based on a lot of investigation. Please post any

questions or comments, because any discussion can help figure out

better guidelines which the group can benefit from. Personal

experiences and anecdotal information are really important at this

point, so please post if you have any to offer. .

Metals, Chelation and Enzymes

Dec 2001, Kd

Please note this is a work in progress. The guidelines given are

loose and any specific course of action needs to consider of the

particular needs and responses of any one individual. This will be

updated as more information becomes available. There are 5 parts:

1. Heavy Metals and Chelation

2. Sulfur in the Body

3. Do Metals and Enzymes Interact with Each Other?

4. Should You Take Digestive Enzymes During Chelation?

5. Does Timing Make a Difference?

References are indicated by the >>>>>>>

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1. Heavy Metals and Chelation

Heavy metals can be toxic in the body and do a lot of damage in a

lot of areas. They can damage nerves and functional pathways

directly or indirectly. They can also cause a wealth of damaging

free-radicals to continue to be produced in the body. Unless the

metals are removed, these problems continue to persist over time.

The process of removing these metals is called chelation.

All ionic particles have an electrical charge, either positive (+)

or negative (-). Many metals have 2 positive charges: mercury, lead,

copper, cadmium. Aluminum has 3 positive charges. Each positive can

bind to one negative. Particles will jump to whatever substance has

the stronger charge. A metal will leave a weak positive charge in

favor of a strong positive charge. This is the basis of metal

removal. You want to add a substance that will attract the metal

with a stronger bond that the one your body is using to hold the

metal.

The word chelate means " claw. " The idea is to grip the element as

you would with your closed hand, or with a claw. With the metal

molecule held by two bonds, it is gripped and there is a good chance

it will stay with the chelator and be escorted out of the body.

Thus, true chelating agents are chemicals with 2 or more binding

groups per molecule so they hold on to the metal atom tightly. If a

metal is bound just by a single bond, this would be similar to

holding it in a cupped hand – not closed around it. Something else

can just bump it off or grab it from there. Think of it as having a

small magnet cupped in your hand and a medium sized metal passes by.

The metal will be held by the magnet in your hand. But if a larger

and stronger magnet passes by the metal, the metal will leave the

magnet in your hand and jump over to the stronger one. Now if you

have the same magnet in your hand, or two small magnets on each

finger, and you close your hand around it, it will be much harder

for a stronger magnet to pull it out. There is an electro-chemical

bond plus a structural barrier to releasing the captured metal.

If a metal contains at least 2 positive charges, it can

be " chelated " or bound to the chelator by two bonds. If it is only

connected by one bond, it will still have another positive charge

with which to bind to something else. If your friend has grabbed

both of your hands to hold onto you, it is much harder to pull you

away from him. However, if he is holding only one of your hands and

your other one is free, another person could come along and grab

your free hand as well. If the second person was much stronger and

wanted to pull you away, he would have a much easier time of it than

if both your hands were held by the first person.

This is why some products are not advised for actual chelating

because, although they draw out mercury and bind to it, the bonding

is not extremely tight. There is a good chance the mercury with

bounce off at some other place in the body while it is being

excreted, and cause damage to the new area when it re-attaches in

the body. Chlorella, cysteine, penicillamine, glutathione, " sulfur

foods, " etc. are not true chelating agents because they only hold

onto the mercury with one bond. They can attract metal ions and draw

them out of hiding places, but they may lose the metal before it

successfully gets transported out of the body.Lipoic acid (as

dihydrolipoate which your body converts it into), DMSA and DMPS each

have TWO thiols or sulfur groups per molecule so they hold onto the

mercury atoms tighter than your body does and have a chance to

really escort the mercury out instead of just stirring it up. Thus

these are CHELATING AGENTS - chemicals with 2 or more binding groups

per molecule so they hold on to the metal atom tightly.

>>>>>>>

there is a lot of information at the autism treatment board and in the

Files section there. Autism-

Mercury/files

>>>>>>>

It is also important to remember that the body and gut is a dynamic

place. There is constant interaction between

foods/enzymes/metals/gut lining/blood stream and other things. So

what you may see as a " reaction " one day may not hold true next

week. During chelation, a chemical gradient is set up and metals

are " stirred up " or put into motion in the body. Chelators go

through and latch on to certain metals or other positively charged

elements, but there are also other loose, unattached metals floating

around. The idea is to keep a steady supply of chelators in motion

as well to grab the metals. How often a chelator is given can be

very important as well as how much. And also how may days " on " and

then " off " you need to give a chelator. The level of chelators needs

to stay at a certain level for a certain amount of time to be

effective. As soon as you stop the chelator and the level drops

significantly, the equilibrium flow is broken and any loose metals

will re-attach wherever they can. This is the re-distribution effect

where metals from one part of the body can end up somewhere else.

When they re-attach, metals can cause damage wherever they end up

(they might not, but they might). It is very common for someone

chelating to have a particularly " bad " reaction or symptoms on the

first day or two " off " the chelator because any loose metals are re-

attaching. If you just randomly give a dose of chelator to a metal

toxic person, it will just keep bringing the metals into solution in

the body, not sufficiently grabbing them and removing them from the

body, and then they re-attach and damage once again. This leads to

the strong warning often heard that if you don't chelate correctly

you could do far more damage than help.

2. Sulfur in the Body

Sulfur is critical to normal bodily function. Sulfur is best known

for its presence in four amino acids: methionine (an essential amino

acid), cystine and cysteine (non-essential amino acids which can be

made from methionine in the body), and taurine (a conditionally-

essential amino acid which can normally be made from cysteine).

Sulfur is also present in two B-vitamins: thiamine and biotin. In

addition, there are many other sulfur-containing compounds of

primary importance in nutrition and metabolism.

In the diet, sulfur amino acids are readily available in animal

protein foods such as meat, fish, poultry, egg yolks, and milk.

Grains and legumes have lower amounts of the sulfur amino acids.

Onions, garlic, cabbage, brussell sprouts, and broccoli also contain

important bioactive sulfur compounds.

>>>>>>>http://www.amni.com/reprints/sulfur.html

Elemental sulfur has a negative charge of 2 (S--). Sulfur is usually

present in organic compounds as sulfhydryl groups, also

called " thiols " . This is written as SH- and means one sulfur atom is

connected to one hydrogen atom (H+), and the entire group has a

single net negative charge. So the sulfur-hydrogen group can bind to

something with a single positive charge. Mercury and many other

metals have 2 positive charges (aluminum has 3). The affinity of

mercury for sulfur is one of the strongest bonding attractions

known. Enzymes such as papain, bromelain, amylase, and lipase, have

sulfhydryl groups. So mercury could also effectively interact with

quite a broad range of digestive enzymes.

>>>>>>>

" Mercury loves sulfur. In the presence of sulfur, mercury will

unbind from virtually any other substance in order to bind with

sulfur. For this reason, sulfur is a member of a class of substances

called 'mercaptans,' which, I believe, is Latin for `mercury

capture.' "

http://www.envirodental.co.uk/articles.asp

>>>>>>>

3. Do Metals and Enzymes Interact with Each Other?

Yes.

All enzymes are proteins made up of amino acids. Some amino acids

have sulfur as part of their structure. Enzymes have unique folding

patterns that give them their shape and function. These folding

patterns are held in place by bonds called disulfide bonds or

bridges. The sulfhydryl group in one spot of the protein will

connect with another sulfhydryl group at another spot in the protein

(thus, 2 sulfurs make a bridge across the protein). This gives the

enzyme its unique 3D shape that usually is directly related to its

ability to function with other compounds. When a metal passes by, it

can break the disulfide bond and attach to one of the sulfhydryl

groups. Breaking the sulfur bridge can distort the delicate

structure of the enzyme and ruin its ability to function. At this

point the metal might continue to stick with the enzyme or it might

not. If another molecule passes, say, with a sulfur group or

chelator for example, the metal might leave the deactivated enzyme

and jump over…perhaps even to another enzyme where it will break

another disulfide bridge and inactivate that one.

>>>>>>>

Shows folding pattern with disulfide (Sulfur-Sulfur) bonds

which " bridge " the protein together and give it its shape. This

particular one is a metalloproteinase and so also has a zinc in it

as the active site. The sulfur bonds may not even be near the active

site.

http://delphi.phys.univ-tours.fr/Prolysis/Images/astacin.jpeg

Multitude of different protein structures - disulfide bonds/bridges

in yellow

http://www.biochem.szote.u-szeged.hu/astrojan/protein1.htm

http://www.biochem.szote.u-szeged.hu/astrojan/protein2.htm

How sulfur containing amino acids create disulfide bonds:

http://www.encyclopedia.com/printablenew/44890.html

Fun 3D site for biochem if you register for their free tool to see it

http://www.chem.uwec.edu/Chem406/Webpages/KAREN/template.html

Shows folding pattern of papain

http://delphi.phys.univ-tours.fr/Prolysis/Images/pap.jpeg

Crop Circles – has nothing to do with this file but interesting to

look at

http://www.biochem.szote.u-szeged.hu/astrojan/Cropcirc.htm

>>>>>>>

It is pretty much agreed by all sources that mercury and other

metals inhibit enzymes because of the sulfhydryl groups. Metals do

not inhibit enzyme action by competing with the enzyme active

binding site. When a metal, such as mercury, binds to a sulfur group

on the enzyme, it may disrupt the activity or the structure of the

enzyme and make it ineffective. After binding, the mercury molecule

may stay bound to the enzyme or it may leave. The idea of consuming

more sulfur foods/supplements with the enzymes during chelation is

based on this. Providing more sulfur in the gut via

food/supplements, or even giving chelating agents with food, will

bind up loose metal ions and competitively keep them from binding

with the sulfur in the enzymes. In this scenario, more enzymes

should eventually override the quantity of metals passing through

the gut, and food digestion will take place. However, another

possibility is that the mercury or other metals attached to an

enzyme, could also then detach from the enzyme and connect to other

foods or supplements (usually attracted to the sulfur group). It

could even detach and go bind to another enzyme, disrupt it, leave,

and then go on, etc. In this scenario, it can be seen that just a

little mercury could inactivate a larger quantity of enzymes. If the

chelator you are consuming is a true chelator that binds the metals

with two bonds, then taking the chelator with enzymes would lessen

the possibility that a metal would be loose and attach to an enzyme.

If the product you are taking attaches to metals mostly by a single

bond, then it will not be as helpful in preventing enzyme

deactivation.

What happens between enzymes, metals, and chelators will depend on

the types of bonding taking place, the particular equilibrium in the

gut, composition of the enzyme and metal ion or group, and

conditions in the gut at any particular moment.

>>>>>>>

Types of Enzyme Inhibition

http://www.sbu.ac.uk/biology/enztech/inhibition.html

" Mercury, as well as some other metals, do bind to sulfhydryl groups

on any protein, including enzymes, but this is not a covalent bond,

but is ionic. The strength of the binding can vary, so yes, the

metal can float on and off, depending upon whether other groups with

higher binding affinity are present. " – Dr. Devin Houston

" Heavy metal ions (e.g. mercury and lead) should generally be

prevented from coming into contact with enzymes as they usually

cause such irreversible inhibition by binding strongly to the amino

acid backbone. "

http://www.sbu.ac.uk/biology/enztech/inhibition.html

>>>>>>>

4. Should You Take Digestive Enzymes During Chelation?

Usually, yes.

Most all sources that commented on this say " yes. " There were no

sources found which said not to. The reason is that the digestive

enzymes provide overall support for the body in a number of ways.

1. immune support

2. free-radical elimination

3. helps control yeast, bacteria and parasites in the gut which can

quickly get out of control during chelation

4. increase nutrition from food and supplements. This nutritional

support helps the body detox and remain healthy during chelation by

supplying all the assisting vitamins and minerals needed (including

selenium, molybdenum, B vitamins, vitamin C and E). It also helps

the body not become deficient in desirable minerals, such as

calcium, magnesium, and zinc, which can be chelated out of the body

along with the other metals. Several vital minerals also have

positive charges and will bind to the chelators.

Several commercial oral chelation products include plant/fungal

digestive enzymes in them as part of the product, or recommend

taking a companion product which contains enzymes.

>>>>>>>

Heavy Metals and Oral Fungal Protease

Oral proteases taken on an empty stomach have been shown to be

absorbed and carried into the blood stream where they are bound to

Alpha2-macroglobulin. The binding of the Alpha2-macroglobulin to

proteases does not inactivate the proteolytic activity of the

protease. However, the complexing of the Alpha2-macroglobulin

ensures the clearance of the protease from the organism. Several

studies have indicated that oral proteases bound to the

macroglobulins hydrolyze immune complexes, proteinaceous debris,

damaged proteins, and acute phase plasma proteins in the blood

stream' It is suggested that oral proteases may help hydrolyze and

remove extra cellular proteins damaged by free radicals, which are

especially susceptible to proteolysis, as mentioned above.

Heavy metals, such as lead (Pb) and mercury (Hg), exert their

poisoning effect by binding to ionizable or sulfhydryl groups of

proteins, including vital enzymes. Once they bind to an essential

functional protein, such as an enzyme, they denature and/or inhibit

it. This interaction of heavy metals to proteins can lead to

degenerating diseases, nerve damage or even death.

Clinical observations have noted that upon high intake of oral

protease, heavy metal concentrations have been significantly

decreased in the blood. Binding of protease to Alpha2-macroglobulin

leads to an activated complex with altered binding affinities and an

increased rate of clearance from the blood by the liver. It is

possible that the activated Alpha2- macroglobulin protease complex

also has a high affinity for heavy metals, leading to their removal

from the body.

It should be noted that protease when taken on an empty stomach is

readily taken up into the mucosa cells of the intestine and passed

into blood circulation. Clinical observations have noted that upon

high intake of proteases, heavy metal concentrations have been

significantly decreased in the blood. This may be due to the

binding of these toxic substances with the supplemental protease

enzymes, facilitating their removal through the kidneys or

intestine, thus avoiding a life-threatening situation of poisoning.

The result may spare other vital proteins, including metabolic

enzymes, in the body.

http://www.enzymeessentials.com/HTML/proteases.html

http://66.70.197.236/Merchant2/merchant.mv?

Screen=PROD & Store_Code=EU & Product_Code=OCA & Category_Code=OCA

http://www.extremehealthusa.com/digestion.html

http://www.liv4evr.com/recommended_products/get_products.asp?

ProdID=18

>>>>>>>

5. Does Timing Make a Difference?

It might.

A chelator will usually have a negative charge and the enzyme sulfur

group will have a negative charge, and so they will not usually

attract or interact with one another one there own. The metal will

have a positive charge and binds to both of these. Because the

positively charged metals are selectively attracted to the negative

SH- groups on certain enzymes (such as papain, bromelain and lipase)

as well as foods and supplements, it may be better to actually

consume these sulfur containing enzymes and a chelator together when

possible. The chelator will bind any metals with a double bond and

thus keep them away from the enzymes in the stomach. Taking the

chelator on an empty stomach is also good because the chelator with

go more directly into the blood stream. It will not get tied up in

the gut reacting to other substances. Also, as explained in the

above reference, if proteases are taken in-between meals, they can

complex with alpha2-macroglobulin and provide better metal removal.

You may need to experiment a little with the particular enzyme and

chelation product you are using to see if there is a difference

based on if you give them both together and or separately. Some

chelation products may indicate whether or not they should be given

with food. This would be a good thing to ask about whenever starting

a new chelation product.

Whether a chelating agent interferes with enzyme activity or not

will probably depend on:

1. the chelating agent - does it truly " grab " the metal and hold

onto it or does it tend to release the metal and allow it to bind

with other compounds as it flows through the body? A chelator that

grabs and holds onto a metal would be more likely to keep metals

from interacting with enzymes

2. the enzymes used – some enzymes contain sulfur compounds, like

bromelain, papain, and lipase among others, and these are much more

likely to interact with metals than enzymes that to not contain

sulfur

3. the composition in the gut at the time – if metals are moving

regularly through the gut, this creates a situation where metals and

enzymes are very likely to interact

4. the composition of the food eaten – depending on how much sulfur

or other cations (calcium, magnesium, zinc, etc.) are also in the

gut will influence how much competition is present for both the

chelator and the metals in transition

Trying to figure out a specific dosing plan for enzymes during

chelation is tough and will need to be determined on an individual

basis. For example, one mother found she could give casein with

enzymes for 2 and half weeks while chelating. She just happened to

give the chelator with enzymes at mealtimes. Then she switched to

giving the chelator at a separate time from the enzymes/meal, and

her son could no longer tolerate casein even with the enzymes

without a negative reaction. This indicates that the chelator

was " protecting " the enzymes in some way. When it was given at a

separate time, the enzymes appear to have been deactivated by metals

moving through the gut.

Other people do not see a problem with enzyme effectiveness for

awhile, and then during or after a particular round, the person has

trouble with a certain food. This usually clears up after the

following round or two. This seems to indicate that there was some

re-distribution of metals in the gut following a particular round

which made the digestion of certain foods problematic, even if

enzymes were used. Further rounds removed this problem. Metals

passing through the body can cause very dramatic reactions which

have nothing to do with enzymes.

On a very positive note, several people who have been chelating

found that they needed to use less enzymes with foods after metal

removal. And that more foods were tolerated, with or without

enzymes, than were previously tolerated before chelation, with or

without enzymes.

>>>>>>>

" Chelation occurs naturally in the body all the time. I don't think

there is a problem taking enzymes and chelators at the same time.

For mercury to harm an enzyme, it would only be while the mercury is

bound to the enzyme, and remember that there are hundreds of other

sources

of sulfhydryl groups in the many other non-enzyme proteins of the

body. Also, the mercury has to be in solution to do its dirty work.

There is probably an equilibrium between solid and dissolved mercury

in the body, which is why multiple rounds of chelation are usually

necessary, one must

drive the equilibrium to dissolving mercury by removing that mercury

already in solution.

My understanding of how the chelators work is that they are

systemic, moving throughout the body, grabbing metals as they go,

and eventually are passed out through the urinary tract or bowels

(which is why some worry about the amount of mercury passing through

the kidneys). I think also that the amount of enzyme in a dose will

be much higher on a molar basis (molecule to molecule basis in terms

of quantity) than the amount of mercury that may be encountered by

the enzyme. As to why some people think enzymes may not be as

effective during the on cycle of chelation, I don't know. Could be

that the general effects of chelation or the presence of the

chelators themselves affect the gut in some way. Or maybe toxicity

is high temporarily as the metals are moved about. "

- Dr. Devin Houston

>>>>>>>

[Guest guest]

,

This looks great and very thorough (no surprise, from you!). Just

wanted to say publicly how much I appreciate all you work. You are

an amazing lady.

Tom is still improving. It's so nice to have that darn " fog " gone

again!

God Bless,

Sally

> The following is based on a lot of investigation.

[Guest guest]

Hi ,

WOW!! You did a great job!

Thank you!!

Valentina

> The following is based on a lot of investigation. Please post any

> questions or comments, because any discussion can help figure out

> better guidelines which the group can benefit from. Personal

> experiences and anecdotal information are really important at this

> point, so please post if you have any to offer. .

[Guest guest]

In a message dated 1/1/2002 12:39:28 PM Pacific Standard Time,

kjorn@... writes:

> Clinical observations have noted that upon high intake of oral

> protease, heavy metal concentrations have been significantly

> decreased in the blood. Binding of protease to Alpha2-macroglobulin

> leads to an activated complex with altered binding affinities and an

> increased rate of clearance from the blood by the liver. It is

> possible that the activated Alpha2- macroglobulin protease complex

> also has a high affinity for heavy metals, leading to their removal

> from the body.

>

,

Sorry this question is so late. I save alot of the messages for future

reading if I don't have time for a certain thread, but want to read it later.

This one I wanted to follow. Can you tell me if you intended for the above

section from your report to be interpretted as " ...upon high intake of oral

protease in or out of the presence of chelating agents, heavy metal

concentrations have been significantly decreased in the blood " ? Just for

clarification, if I interpret it that way, then there may be an extreme up

side to administering Peptizyde regularly on an empty stomach (like at

bedtime). Am I way off base here, or am I reading this correctly? I f I am

reading it correctly, do you have a feel for what " " high intake " means?

Amber