ATP Profile Results

[Guest guest]

I got results from BioLab's ATP tests and wanted to offer them to the list.

Does anyone have a good understanding of these (like how Mg plays into this,

what the [TL] measurements are, etc)? I know some can be affected by

deconditioning (I am extremely deconditioned), but I assume not all. Pretty

much all

measurements are abnormal. In fact, the [TL]'in' % change required them to

write in an extra description by hand, " very poor, " that was not on their

original form. That can't be good news.

ATP studies on neutrophils

ATP whole cells:

With excess magnesium added: 1.37 (1.6-2.9)

Endogenous magnesium only: 0.85 (0.9-2.7)

Ratio ATP/ATP(Mg): 0.62 (>0.65)

=> ATP low, ATP-related Mg low

Conclusion: low ATP and poor ATP-related Mg availability

ADP to ATP conversion efficiency (whole cells):

ATP(Mg) (excess Mg): 1.37 (1.6-2.9)

ATP(Mg) (inhibitor present): 0.79 (<0.3)

ATP(Mg) (inhibitor removed): 0.94 (>1.4)

ADP to ATP efficiency: 25.8% (>60%)

è Inhibitor site partially blocked

Conclusion: Partial block (58%) of active site leading to very poor

reconversion of ADP to ATP.

ADP-ATP translocator [TL] (mitochondria, not whole cell)

Start: 282 (290-700)

[TL] out: 347 (410-950) 23.1% (>35%) function poor

[TL] in: 202 (140-330) 28.4% (>55%) function very poor

Conclusion: very poor ATP production from the mitochondria, secondary to the

chemical block at the TL] site

Cell-free DNA in blood plasma: 20.6 (up to 9.5)

Conclusion: significant increase in cell degradation

[Guest guest]

Hi, Jim.

***Thanks for posting these results. I don't understand everything

about the interpretation of this test panel yet, but I'll tell you

what I think I do know. See comments at asterisks below.

>

> I got results from BioLab's ATP tests and wanted to offer them to

the list.

>

> Does anyone have a good understanding of these (like how Mg plays

into this,

> what the [TL] measurements are, etc)? I know some can be affected

by

> deconditioning (I am extremely deconditioned), but I assume not

all. Pretty much all

> measurements are abnormal. In fact, the [TL]'in' % change

required them to

> write in an extra description by hand, " very poor, " that was not

on their

> original form. That can't be good news.

>

> ATP studies on neutrophils

***First, some introductory comments: This test panel is run on

neutrophils, which are the most abundant type of white blood cells.

It therefore reflects what's going on with the ATP in the

neutrophils, which is probably more or less related to what's going

on in other types of cells in the body. Neutrophils are chosen

because it is easy to get them by taking a blood sample, and they

have lots of mitochondria.

***The test panel analyzes several things related to ATP. ATP is

the molecule that is produced by adding a phosphate group to an ADP

molecule in the mitochondria, which are the power plants of the

cell. The energy for this phosphorylation comes from burning food as

fuel, and this conversion of energy is done in the mitochondria by

the Krebs cycle and the respiratory chains.

***After the phosphorylation, the ATP is exported from the

mitochondrion in order to be used to power a whole range of

different biochemical reactions in the cell. In order to be used in

this way, ATP must bind a magnesium ion. After it is used, it loses

a phosphate group and becomes ADP. The ADP then has to be

transported back into a mitochondrion to be phosphorylated again.

***The transport of ATP out of the mitochondria and the transport of

ADP back into the mitochondria is accomplished by a protein molecule

in the inner mitochondrial membrane that is called the ADP-ATP

translocator. This is the most abundant protein in the inner

mitochondrial membrane. During the transport, the ADP and ATP are

not bound to magnesium ions. The phosphate is transported back into

the mitochondria using another transporter, so that it can be

reattached to the ADP inside the mitochondria, to make ATP again,

using energy derived from oxidizing food. This overall process is

called oxidative phosphorylation.

***O.K., now let's look at the test results.

***The first part evaluates the amount of ATP and the magnesium

availability to the ATP in whole neutrophils:

> ATP whole cells:

***The first measurement is done adding extra magnesium. This is

done because they are using a reaction to evaluate how much ATP is

there, and in order to evaluate total ATP, they don't want the

reaction rate to be limited by whether or not the ATP molecules can

find enough magnesium. Remember that they can't react unless they

have bound magnesium. So they add extra so that they can just

measure total ATP. Note that they find in your case that your

neutrophils have less than the normal range of total ATP:

> With excess magnesium added: 1.37 (1.6-2.9)

***(To find out why there isn't enough ATP, we will have to read

further on in the test results.)

***The next measurement of ATP is made without adding extra

magnesium. It will come out lower, but how much lower will depend

on how scarce magnesium is in the neutrophils. Note that in your

neutrophils this measurement also comes out lower than the normal

range, meaning that your neutrophils do not have enough magnesium:

> Endogenous magnesium only: 0.85 (0.9-2.7)

***(Why not? Well, that isn't explained by this test. We do know,

however, that most PWCs are low in intracellular magnesium. It's

probably a vicious circle. It takes ATP to pump magnesium into the

cells, and it takes magnesium to signal the mitochondria to make

more ATP. In my opinion, this magnesium issue may be one reason for

the reported benefit of the Blasi protocol, because it makes

magnesium more available to the cells.)

***So then they take the ratio of these two, and that clinches the

argument that your neutrophils don't have enough magnesium:

> Ratio ATP/ATP(Mg): 0.62 (>0.65)

***And then they give the conclusions from this part of the test

panel: your total amount of ATP is lower than normal, and the

amount of magnesium that is available to bind to ATP is also below

normal:

> => ATP low, ATP-related Mg low

>

> Conclusion: low ATP and poor ATP-related Mg availability

>

***O.K., so now they go on to measure some parameters that will

indicate how efficiently the mitochondria in your neutrophils are

able to convert ADP to ATP:

> ADP to ATP conversion efficiency (whole cells):

***The first number is just a repeat of the first thing they

measured, i.e. the amount of ATP observed to be reacting when there

is excess magnesium added:

>

> ATP(Mg) (excess Mg): 1.37 (1.6-2.9)

***Then they add an inhibitor that prevents the conversion of ADP to

ATP. I think this inhibitor acts on the enzyme that does this

conversion, which is called ATP synthase. This causes the ATP in the

cells to drop in a short period of time, because it is being used by

reactions, and thus converted to ADP, but the conversion back to ATP

by oxidative phosphorylation is being prevented by the inhibitor.

How much the ATP drops will depend on how well the inhibitor is able

to shut off ATP synthase, and how well the reactions that use ATP

are able to use it. In the case of your neutrophils, it didn't drop

as much as is normal:

> ATP(Mg) (inhibitor present): 0.79 (<0.3)

***Then they remove the inhibitor and measure how much the

ATP comes back up. Yours didn't come up as far as is normal:

> ATP(Mg) (inhibitor removed): 0.94 (>1.4

***Then they calculate how much it rose as a percentage of how much

it dropped from the original value. Yours rose only 25.8% of how

much it dropped, compared to a normal value of at least 60%:

> ADP to ATP efficiency: 25.8% (>60%)

***Based on this behavior, they conclude that the molecular site on

the enzyme used by the inhibitor is partially blocked. I think that

would explain why the drop was not as large as normal when the

inhibitor was added:

> è Inhibitor site partially blocked

***What would cause this blockage? This test doesn't tell that, but

it is suggested on the Biolab website that it is a chemical toxin.

***The overall conclusion from this part of the test is that the

active site of the enzyme used to convert ADP to ATP is partially

blocked, and that there is consequently very poor reconversion of

ADP to ATP:

>

> Conclusion: Partial block (58%) of active site leading to very

poor

> reconversion of ADP to ATP.

***Now at this point I think they are missing something, and that is

that if there are partial blockades in the Krebs cycle and/or the

respiratory chains, this could also contribute to a poor rate of

reconversion of ADP to ATP, which is where I think the rise of

superoxide as a result of depletion of glutathione comes into the

picture. I'm continuing to discuss this with Dr. Myhill.

***Next, they take the mitochondria out of the neutrophils, and they

study them separately in order to see how well the ADP-ATP

translocators are working:

>

> ADP-ATP translocator [TL] (mitochondria, not whole cell)

***First, they evaluate how much total ATP there is in the

mitochondria. Again, yours come out quite low:

>

> Start: 282 (290-700)

***Then, they bias the translocators so that it is easy for them to

import ADP, but hard to export ATP. I'm not sure how they do this,

but I think it is an electrical bias. Under this situation, the

mitochondria should make ATP from the ADP. Yours didn't make as

much as normal:

> [TL] out: 347 (410-950) 23.1% (>35%) function poor

***Then they bias the translocators in the other direction, and the

ATP should drop. In your case, it did not drop as much as normal:

> [TL] in: 202 (140-330) 28.4% (>55%) function very poor

***From this, they conclude that that the mitochondria are not

producing ATP very well, and they say that this is caused by a

chemical block at the translocator site:

>

> Conclusion: very poor ATP production from the mitochondria,

secondary to the

> chemical block at the [TL] site

***What would cause such a block? The Biolab website suggests

intracellular acidosis or excess intracellular calcium. It also

suggests the possibility of a translocator defect.

***Again, here's a place I think they are missing something. I

think the poor ATP production measured here does not necessarily

have to be due to a chemical block at the translocator site. It

seems to me that this result could be caused by problems in the

oxidative phosphorylation system, including the Krebs cycle and the

respiratory chains, such as by rise of superoxide secondary to

glutathione depletion, as I mentioned above.

***Next, they measure how much DNA is floating around free in the

blood plasma, outside cells. Yours came out higher than normal:

>

> Cell-free DNA in blood plasma: 20.6 (up to 9.5)

***Since DNA is normally supposed to be inside the nucleus of cells,

if there is more than a normal amount of it floating around free, it

means that the rate of death of cells (necrosis) is higher than

normal:

>

> Conclusion: significant increase in cell degradation

***Why would that happen? Well, perhaps because of low cellular

energy, owing to these ATP problems.

***So this test seems to be showing that your neutrophils have

deficits in every aspect of the production and use of ATP that they

measured. It's not clear from this test exactly why, but it does

tell you that there definitely are problems with the mitochondria in

your neutrophils, and presumably in other cell types as well, since

they would be subject to the same issues of nutrition and toxicity

that the neutrophils are.

***I guess that's the best I can do with this, Jim.

Rich

[Guest guest]

Rich,

Thanks much for the interpretations!

2 follow-ups:

1) can a virus and/or immune system dysfunction (e.g. RNase L problems) be

the cause of any of the results?

2) do you have a sense if any of these atp tests can be worse due to

deconditioning? and why is one's aerobic capacity lower in deconditioning? is

it the

number of mitochondria is lower? o2 uptake is less? or perhaps lower levels

of enzymes?

I asked Biolab a few months ago, and got a vague answer deconditioning can

affect atp levels, but it would not explain at least some of the test results.

I ask because I am extremely deconditioned. However, ever since getting CFS,

my anaerobic threshold was lower right from the get-go, even when I was in

shape.

I may send this to McCully. He looked at my data from the aerobic

metabolism study, specifically using M.R.Spectroscopy on my calf muscle in the

recovery phase of exercise. It was his opinion that my poor function was due to

more than just deconditioning. But with M.R.S., it is difficult to discern

what is going on inside the cells to cause such dysfunction, even

differentiating between deconditioning and disease.

Thanks again,

Jim

[Guest guest]

Rich, since there is a partial block of both the ATP synthase

inhibitor site and the ATP synthase active site (which are presumably

distinct), perhaps some upregulated small chaperone could be

interacting with both sites - just a wild speculation really.

Some CFS PBMC proteomics would be a nice complement to Gow and Kerrs

work, in case there might exist some proteins that are differentially

regulated in CFS vs health, but differentially regulated thru

channels other than mRNA abundance.

Since I take a really comparative approach to CFS, I'm dying to know

whether similar ATP findings exist in any other disease states. If

anyone has such info please let me know.

Rich wrote:

***Again, here's a place I think they are missing something. I

think the poor ATP production measured here does not necessarily

have to be due to a chemical block at the translocator site. It

seems to me that this result could be caused by problems in the

oxidative phosphorylation system, including the Krebs cycle and the

respiratory chains, such as by rise of superoxide secondary to

glutathione depletion, as I mentioned above.

[Guest guest]

Hi, Jim.

>

> Rich,

>

> Thanks much for the interpretations!

>

> 2 follow-ups:

>

> 1) can a virus and/or immune system dysfunction (e.g. RNase L

problems) be

> the cause of any of the results?

I guess I would have to say that I think it could. The reason I say

that is that RNase-L chops up messenger RNA, which is used to

translate the genes into enzymes. Some of the enzymes coded for in

the cell nucleus are needed by the mitochondria, so it seems to me

that if this process is interfered with, it could have an impact on

the ability of the mitochondria to do their job of making ATP. One

thing I'm not sure of, though, is whether RNase-L is active in the

neutrophils in PWCs. As far as I know, all the RNase-L studies have

been done in peripheral blood mononuclear cells (lymphocytes and

monocytes). Prof. Suhadolnik told me that all cells are capable of

producing RNase-L, though.

>

> 2) do you have a sense if any of these atp tests can be worse due

to

> deconditioning?

***I doubt if deconditioning would affect the neutrophils, so I

don't think so. If the test were run on muscle cells, it might be

possible.

and why is one's aerobic capacity lower in deconditioning?

is it the

> number of mitochondria is lower? o2 uptake is less? or perhaps

lower levels

> of enzymes?

***I'm not sure. That's a good question. The answer is probably

known. I'll have to study that.

>

> I asked Biolab a few months ago, and got a vague answer

deconditioning can

> affect atp levels, but it would not explain at least some of the

test results.

***I just gave you a vague answer, too, didn't I? Maybe I can do

better if I dig around a little.

> I ask because I am extremely deconditioned. However, ever since

getting CFS,

> my anaerobic threshold was lower right from the get-go, even when

I was in

> shape.

***As you probably recall, I don't think the issue in CFS is

deconditioning. I think the cells demand less oxygen because their

oxidative metabolism has partial blockades due to a rise in

superoxide, secondary to glutathione depletion. I think that would

give the rapid drop in anaerobic threshold that you experienced,

though you were still in good shape in terms of your muscle size and

recent use.

>

> I may send this to McCully. He looked at my data from the

aerobic

> metabolism study, specifically using M.R.Spectroscopy on my calf

muscle in the

> recovery phase of exercise. It was his opinion that my poor

function was due to

> more than just deconditioning. But with M.R.S., it is difficult

to discern

> what is going on inside the cells to cause such dysfunction, even

> differentiating between deconditioning and disease.

***I think that if we were smart enough, we would be able to combine

an ATP profile test (it would be better if done on cells from a

muscle biopsy than on neutrophils) with a cardioexercise test, an

MRS test of the muscle, and quantitative histology of the biopsied

muscle, and run this on PWCs and on normals with various degrees of

conditioning, and figure it all out. I don't think we're there yet,

though, and it would take quite a team and a lot of bucks to do it,

so maybe we will have to substitute some clever thinking.

>

> Thanks again,

>

> Jim

***You're welcome.

***Rich

>

>

>

[Guest guest]

Hi, .

Thanks for the comments.

I don't know the details of what is used as the inhibitor in this

test or where it binds, so I can't go much further on that yet. I'm

hopeful that McLaren will publish more about this test

panel soon. I think he has something submitted to a journal.

I agree with you on the need for looking at the proteomics, and I

think things are moving that way. At the NIH workshop in June,

2003, Dr. Eleanor Hanna, who coordinates CFS work at the NIH, said

to me as soon as I met her that the proteomics will be the key,

before I had had a chance to say anything! Also, I think the CDC

has this in their published research plan. Also, you may know that

Jim Baraniuk et al from town published a paper a few months

ago on proteomics of the spinal fluid in CFS, which revealed a

problem with protein folding. He agreed with me that glutathione

depletion is a possible explanation for that, and said they would

follow up on that possibility. So I think we will be seeing more of

proteomics in CFS soon.

That's a really good question about ATP problems in other disease

states. I'm going to guess that any disorder that involves fatigue

is going to involve problems with ATP generation, but the causes may

be different, and the detailed results of the ATP profile test will

likely be different as well. I'll bet is trying out his test

on a range of disorders right now!

At the OHM meeting, I told Dr. Shallenberger about this test

panel and suggested that he get in contact with and do some

of the same patients. Shallenberger does a rather sophisticated

analysis of oxygen and CO2 before and during use of an exercise

bike. He calculates what fraction of the power is coming from carbs

and how much from fat-burning, and a bunch of other parameters. I

think it would be interesting to see a correlation, one looking at

mitochondria, the other looking at energy production by the whole

organism.

Rich

>

> ***Again, here's a place I think they are missing something. I

> think the poor ATP production measured here does not necessarily

> have to be due to a chemical block at the translocator site. It

> seems to me that this result could be caused by problems in the

> oxidative phosphorylation system, including the Krebs cycle and the

> respiratory chains, such as by rise of superoxide secondary to

> glutathione depletion, as I mentioned above.

>

[Guest guest]

rich,

i've tried to absorb all your comments about my atp profile, and i have a few

follow-ups:

1) as for why the amount of atp measured is higher when excess magnesium is

added, is it because the magnesium stimulates the mito to produce more atp i

nthe cell, or is there already more atp in the cell, it's just not measured by

their tests because there is not enough magnesium to link up with?

2) i'm a bit confused on the testing methods - when something is added or

blocked, are tests run after some time until a new steady state has been

established? i'm trying to understand, for example, after an atp synthase

inhibitor

is removed, why my atp levels don't, over time, go back to my (low) nominal

state. i mean, what would be different in the long run in the cell after the

addition and removal of the inhibitor?

3) it looks like when mg is added, my atp level reaches the normal range of a

healthy person (who was not given mg); so can i simply say if i can get that

much mg into my cells, i will have an acceptable level of atp? (or was this a

1-time snapshot, and my mito would not be able to keep up with the added

magnesium's impetus to create more atp?)

4) are they suggesting a blocked site on atp synthase is responsible for not

only a reduced ability to make atp, but also a reduced ability for the

inhibitor to affect it?

5) i don't see how your theory of a blockade in the kreb's cycle can explain

all my abnormalities. i take it it can explain these abnormalities:

a) the low atp in the mito and cell, and

the poor generation of atp after the [tl] bias is set to let adp in, and

c) the poor recovery in atp after the atp synthase inhibitor is removed.

but i don't see how it can explain:

a) the smaller decrease in atp levels when an atp synthetase inhibitor was

applied, nor

the smaller decrease in atp level when the [tl] bias is set to promote atp

exit of the mito

c) possibly the low magnesium levels (though as you said, if there's low atp,

that could potentially explain it as there is not enough atp to bring in

enough mg).

i guess if i was just " clogged up " everywhere (the kreb's cycle, atp

synthase active sight, and [tl] receptors) it could explain it. or perhaps gene

expression abnormalities in multiple metabolic areas? it seems tempting to think

the lower than normal reduction in atp in 2 diferent tests should almost be

related somehow at least, don't they? i guess it seems more reasonable to

think there are only 1 or 2 root causes than many, independent ones.

6) does anaerobic metabolism not take place in neutrophil cells?

sorry for all the questions, but this is quite fascinating.

no rush. and thanks again!

jim

[Guest guest]

Rich,

Will try to track down some of this. If I get anywhere, will post.

I asked about anaerobic contributions, because I wondered if my lower than

expected drops in ATP levels could be because of a contribution from glycolysis,

but I may be way off on that. And also if perhaps pH levels interfered at

all.

Forgot, there was still 1 answer you gave that I didn't quite get, and can't

quite figure out from their website.

It's the test where the [TL] is favored to block ADP out. My mito ATP level

dropped to 202 (140-330), % drop was 28.4% (> 55% decrease). I thought this

was a measurement of the working ability of the [TL] to shuffle ATP out of the

mitochondria. But they say this measures the normal use of ATP. Not sure what

they mean by " use, " and where (in the mito, or outside the mito).

Thanks,

Jim

[Guest guest]

Rich,

I think I just found out what was meant regarding my ATP level not dropping

as much as it should. They say it could reflect a problem in the hydrolysis

(use) of ATP. Wow, so potentially a problem of creating ATP and a problem with

using it? Sounds like my ATP just isn't popular.

Anyway, perhaps the inhibitor-related abnormalities and the [TL]-related

abnormalities (and the rest) could all be explained by poor oxidative metabolism

AND poor hydrolysis. I wonder if those 2 processes have something in common

which could cause a malfunction in both of them.

Jim

[Guest guest]

Hi, Jim.

***You've given me some real posers here! These are the types of

things I'm still trying to understand, too, so I will try to

struggle along with you on them. I don't have the last word on this

stuff yet.

>

> rich,

>

> i've tried to absorb all your comments about my atp profile, and i

have a few

> follow-ups:

>

> 1) as for why the amount of atp measured is higher when excess

magnesium is

> added, is it because the magnesium stimulates the mito to produce

more atp i

> nthe cell, or is there already more atp in the cell, it's just not

measured by

> their tests because there is not enough magnesium to link up with?

***Personally, I think it's the former, based on the relative values

of the is constants for binding magnesium that are exhibited

by ATP and the enzyme pyruvate dehydrogenase phosphatase. However,

I think Dr. believes it is the latter. I've been having a

dialogue with Dr. Myhill about this, and Dr. is also

commenting on her draft manuscript, so maybe we will get to a

meeting of the minds.

***My argument goes like this: Different enzymes have different

affinities for their cofactors, as evaluated by the is

constant. The higher the affinity, the lower the is

constant, and vice versa. In the case of magnesium, the enzyme

pyruvate dehydrogenase phosphatase has about 5 orders of magnitude

lower affinity for magnesium than ATP does. So when magnesium

starts becoming scarce intracellularly, the shortage should become a

problem for pyruvate dehydrogenase phosphatase before it does for

ATP. Pyruvate dehydrogenase phosphatase is what activates the

pyruvate dehydrogenase complex to convert pyruvate from glycolysis

into acetyl CoA to be fed into the Krebs cycle. So this is a

feedback mechanism in the mitochondrion. Normally, if there is a

high charge of ATP, it will tie up magnesium ions, and that will

lower the concentration of free magnesium ions, thus signalling

pyruvate dehydrogenase to deactivate, and that will lower the flow

of pyruvate into the Krebs cycle, because not as much flow is needed

if there is already enough ATP. However, in CFS, I believe that

intracellular magnesium is lowered for another reason, and this

fools the feedback system and lowers the ATP production even though

there isn't enough ATP. I suspect that there is a vicious circle

lowering the intracellular magnesium in CFS. That is, the ATP is

driven down by glutathione depletion, and that gives less energy to

power the ion pumps that maintain the intracellular magnesium

concentration, so it goes down.

> 2) i'm a bit confused on the testing methods - when something is

added or

> blocked, are tests run after some time until a new steady state

has been

> established? i'm trying to understand, for example, after an atp

synthase inhibitor

> is removed, why my atp levels don't, over time, go back to my

(low) nominal

> state. i mean, what would be different in the long run in the

cell after the

> addition and removal of the inhibitor?

***I don't completely understand this, either. I suspect that the

inhibitor might not be completely removed. But I think he has taken

that into account by comparing you to the range for healthy, normal

people. I think the reactions are pretty fast, so he doesn't have

to wait very long, but I don't have the numbers for how long.

>

> 3) it looks like when mg is added, my atp level reaches the normal

range of a

> healthy person (who was not given mg); so can i simply say if i

can get that

> much mg into my cells, i will have an acceptable level of atp? (or

was this a

> 1-time snapshot, and my mito would not be able to keep up with the

added

> magnesium's impetus to create more atp?)

***I think that if you had more magnesium intracellularly, it would

help the ATP production, but as I said above, I think this is part

of a vicious circle. Until you fix the glutathione depletion, I

don't think you will be able to raise intracellular magnesium much.

>

> 4) are they suggesting a blocked site on atp synthase is

responsible for not

> only a reduced ability to make atp, but also a reduced ability for

the

> inhibitor to affect it?

***That's how it seems to me from what they say in the writeup, but

I'm not totally sure.

>

> 5) i don't see how your theory of a blockade in the kreb's cycle

can explain

> all my abnormalities. i take it it can explain these

abnormalities:

>

> a) the low atp in the mito and cell, and

> the poor generation of atp after the [tl] bias is set to let

adp in, and

> c) the poor recovery in atp after the atp synthase inhibitor is

removed.

>

> but i don't see how it can explain:

>

> a) the smaller decrease in atp levels when an atp synthetase

inhibitor was

> applied, nor

> the smaller decrease in atp level when the [tl] bias is set to

promote atp

> exit of the mito

> c) possibly the low magnesium levels (though as you said, if

there's low atp,

> that could potentially explain it as there is not enough atp to

bring in

> enough mg).

***I don't totally understand all this yet, either, Jim, and I need

to sit and think about it some more. I do think that glutathione

depletion can put a monkey wrench into the Krebs cycle and the

respiratory chain by allowing superoxide to rise. I believe that

the resulting lower ATP production can lower the intracellular

magnesium, as I described above. I also believe that glutathione

depletion can allow the buildup of toxins in the body, and that

perhaps one or more of these can bind to either the translocator or

the ATP synthase enzyme, and may in that way account for problems

with them, too. In other words, I do think that glutathione

depletion can affect the mitochondria in several ways, and may

account for all the deficits observed. But you have probably

thought more than I have about this at this point! I need to find

time to concentrate on this a little more.

>

> i guess if i was just " clogged up " everywhere (the kreb's

cycle, atp

> synthase active sight, and [tl] receptors) it could explain it.

or perhaps gene

> expression abnormalities in multiple metabolic areas? it seems

tempting to think

> the lower than normal reduction in atp in 2 diferent tests should

almost be

> related somehow at least, don't they? i guess it seems more

reasonable to

> think there are only 1 or 2 root causes than many, independent

ones.

***Right. See above.

>

> 6) does anaerobic metabolism not take place in neutrophil cells?

>

> sorry for all the questions, but this is quite fascinating.

>

> no rush. and thanks again!

***I don't know for sure, but I would think that if the oxidative

metabolism got jammed up enough, the neutrophils could stay alive by

using anaerobic glycolysis. But I haven't studied this, so I'm only

guessing here. If you go to PubMed and put in neutrophil and

glycolysis, you might find some interesting abstracts.

>

> jim

>

***Rich