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Q: statin drugs and interruption of coenzyme q10 pathway ( Answered 5 out of 5 stars,   3 Comments )
Question  
Subject: statin drugs and interruption of coenzyme q10 pathway
Category: Health
Asked by: olsen-ga
List Price: $50.00
Posted: 22 Aug 2004 07:01 PDT
Expires: 21 Sep 2004 07:01 PDT
Question ID: 391066
how specifically do statins (Lipitor) interrupt the manufacture in the
body of coenzymeq10?  what are all the steps involved  in the coenzymeq10 pathway
and where do statins stop this pathway?
Answer  
Subject: Re: statin drugs and interruption of coenzyme q10 pathway
Answered By: livioflores-ga on 25 Aug 2004 23:11 PDT
Rated:5 out of 5 stars
 
Hi again olsen!!


First of all we need to know how the CoQ10 is synthetized in the body:
"Biosynthesis:
Coenzyme Q10 is synthesized in most human tissues. The biosynthesis of
coenzyme Q10 involves three major steps: 1) synthesis of the
benzoquinone structure from the amino acids, tyrosine or
phenylalanine, 2) synthesis of the isoprene side chain from
acetyl-coenzyme A (CoA) via the mevalonate pathway, and 3) the joining
or condensation of these two structures. The enzyme
hydroxymethylglutaryl (HMG)-CoA reductase plays a critical role in the
regulation of coenzyme Q10 synthesis as well as the regulation of
cholesterol synthesis"
From "Coenzyme Q10, Linus Pauling Institute's Micronutrient Information Center"
http://lpi.oregonstate.edu/infocenter/othernuts/coq10/ 


Now we continue with the synthesis of the cholesterol, see the
following article at Wikipedia:
"Synthesis:
Cholesterol is primarily synthesized from acetyl CoA through the
HMG-CoA reductase pathway in many cells/tissues. About 20-25% of total
daily production (~1 g/day) occurs in the liver, other sites of higher
synthesis rates include the intestines, adrenal glands and
reproductive organs."
"Cholesterol - Wikipedia, the free encyclopedia"
http://en.wikipedia.org/wiki/Cholesterol


Third step, the HMG-CoA reductase pathway:
"The HMG-CoA reductase pathway is an important cellular metabolic
pathway present in virtually all organisms. It forms hydrophobic
molecules for tasks as diverse as cell membrane maintenance, hormones,
protein anchoring and N-glycosylation.
·Reactions:
    * Acetyl-CoA (citric acid cycle) and acetoacetyl-CoA to
3-hydroxy-3-methylglutaryl-CoA (HMG-CoA);
##  * HMG-CoA to mevalonate - by HMG-CoA reductase; 
    * Mevalonate to Isopentenyl-pyrophosphate (IPP) - by mevalonate kinase;
    * IPP to geranyl-PP by farnesyl-PP synthetase
    * Geranyl-PP to farnesyl-PP by farnesyl-PP synthetase.


Farnesyl-PP is perhaps the central product of the pathway. It is
metabolised further by a number of steps into:
##  * Cholesterol
    * Prenylation chains
    * Haem A
    * Dolichol (plays a role in glycosylation of proteins)
##  * Ubiquinon (essenial in protein catabolism)"
From "HMG-CoA reductase pathway - Wikipedia, the free encyclopedia"
http://en.wikipedia.org/wiki/HMG-CoA_reductase_pathway


See the following image for better understanding:
"HMG-CoA reductase pathway":
http://en.wikipedia.org/wiki/Image:HMG-CoA_reductase_pathway.png


NOTE: take in account the marks ## made to the second step of HMG-CoA
reductase pathway, and to its products cholesterol & Ubiquinon (also
known as Coenzyme Q10), I will recall for these marks at the end of
the following paragraph.


STATINS:
The statins are medicines that are used to lower cholesterol levels in
patients with hypercholesterolemia. They act by competitively
inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase,
an enzyme of the HMG-CoA reductase pathway, the first step of body's
metabolic pathway for the synthesis of cholesterol.
Atorvastatin (LIpitor) is a drug of this family, it is an inhibitor of
HMG-CoA reductase, the rate-limiting enzyme that converts
3-hydroxy-3-methyl-glutaryl-coenzyme A to mevalonate, a precursor of
sterols, including cholesterol.


Now I recall the marks ## and make a summary:
· Statins (such Lipitor) are inhibitors of HMG-CoA reductase.
· Cholesterol and CoQ10 are syntethized via the HMG-CoA reductase pathway.

CONCLUSION: 
Lipitor inhibit the biosynthesis of both CoQ10 and cholesterol.


With the above background you can go to the following article that
will illustrate you about all the steps involved in the CoQ10
synthesis and where do statins stop it very clearly, I strongly
suggest you to read it (see the figure 1 at page 3):
"Coenzyme Q10, Lipid-Lowering Drugs (Statins) and Cholesterol: A
Present Day Pandora?s Box" by Emile G. Bliznakov, MD; from The Journal
of the American Nutraceutical Association, Vol. 5, No. 3, Summer 2002
:
http://www.americanutra.com/reprints/CoQ10Reprint.pdf



Additional references:
"ALL Statin Drugs Reduce or Eliminate Natural CoEnzyme Q10 Synthesis
Jun, 10 2004":
http://www.advancedlifeproducts.com/full.php?ID=177


"Atorvastatin Reduces Blood CoQ10 Levels" by Laurie Barclay, MD:
http://www.medscape.com/viewarticle/481425


"Atorvastatin Decreases the Coenzyme Q10 Level in the Blood of
Patients at Risk for Cardiovascular Disease and Stroke" by Rundek T,
Naini A, Sacco R, Coates K, DiMauro S.
Journal of Neurology, July 2004: Cite:Arch Neurol. 2004;61:889-892.
See the abstract at PubMed:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15210526

Full text access ($12):
http://archneur.ama-assn.org/cgi/content/full/61/6/889

----------------------------------------------------------------

Search strategy:
q10 synthesis
statin q10 synthesis
mevalonate pathway
farnesyl pyrophosphate q10
"Coenzyme Q10 synthesis" process


I hope that this helps you. Again feel free to request for any
clarification needed before rate this answer.


Best regards.
livioflores-ga
olsen-ga rated this answer:5 out of 5 stars
thank you again.

Comments  
Subject: Re: statin drugs and interruption of coenzyme q10 pathway
From: dr_bob-ga on 23 Aug 2004 21:45 PDT
 
olsen

1.) Your questions regarding statins are complicated, and would take
someone with skill several days to put together a good quality answer.
 Be patient.

2.) The amount of money you have offered is more than fair. 

3.) If I were a google answerer, I could put together something to get
you going.  But I'm not, and I don't do this kind of work for free.

Chugs.
Subject: Re: statin drugs and interruption of coenzyme q10 pathway
From: olsen-ga on 02 Sep 2004 19:17 PDT
 
to dr. bob-ga.  Just how much would you charge to answer my questions?
 I need information that will help convince my treasured niece's
physician husband(he is 57 yrs. of age) and all his physician friends
that the parkinson symptoms he is exhibiting is due to the Lipitor he
has been taking for 5 yrs. and he continues to take.  to compound the
problem, he has been started on the gold standard of Parkinson
therapy--L-Dopa and Carbidopa--they've started the clock ticking on
him (the explanation the neurologist gave my husband for not starting
him on l-dopa just now in the early onset stages of the disease--the
side effects of the dopamine replacement drugs after 5 yrs. are almost
as debilitating as the disease itself.  and they are neurotoxic--guess
that accounts for the severe side effects.)  My husband (60 yrs of
age) was diagnosed 2 weeks ago with Parkinson's.  4 months prior to
their diagnoses, my niece and i discussed our husands' symptoms to
discover they were eerily similar. Both men were on Lipitor--the only
drug my husband was on and one of 2 her husband was on--and had been
on it for more than 4 yrs. each. when reading about Lipitor, the fact
that one of the "unintended consequences" of profound depletion of
coenzyme q10 was alarming.  My husband stopped the lipitor and began
coq10 at a normal dose of 100mgm.  we thought equating the coq10
depletion from the Lipitor with his newly acquired neurological
symptoms was simplistic and wishful thinking--maybe if he stopped the
offending agent, and replenished his coq10 stores, all would resolve. 
As the symptoms increased he consultd a neurologist who made the
diagnosis of parkinson's and recommended he take only one supplement: 
coenzyme q10 in a megadose of 1200mgm/day.  we no longer feel it so
simplistic to associate the onset of neurological symptoms with the
Lipitor. The neurologist had never heard of statins associated with
any neurological problems--neither did the second neurologist we
consulted.  In fact he was rather perturbed we even mentioned the
possibility lipitor was related to the parkinson's.  and of course my
husband's internist and any other physician with whom he has discussed
this think we are hysterically searching for the "magic bullet".  Yes,
we are, but with some very plausible science behind it.  If I just
understood all the science behind it.  I took organic chemistry 35
yrs. ago--and much has changed including my ability to comprehend.
hence the reason i asked for the explanation to be something i can
understand.  The information would also help us with
finding/convincing a neurologist who could THINK about the possibility
of this neurological problem being one of a statin toxicity and treat
it from that standpoint.  we are also convinced there must be a subset
of payients out there who have developed neuromuscular symptoms due to
statins.  i have encountered evidence that patients think their
Amyotrophic lateral sclerosis diagnosis may be associated with
statins.  Just read the "ask the experts" column on the Muscular
dystrophy association web site under ALS--there are 3 questions of the
16 printed since feb, 2004, that specifically ask if one of the
statins has anything to do with the symptoms they are experiencing
that have been diagnosed as ALS. Yes, I know this is all anecdotal. 
like the drunk on his hands and knees under the light post.  the
policemen asks him what he's doing and he answers he is looking for
his keys  he lost in the alleyway.  When the policeman points out that
the alleyway is behind him and not under the lamp post , the drunk
points out "yes, but this is where the light is". this is a very
long-winded explanation of our current position.  again, how much
would you charge?  and do you know of anyone in science who would even
consider this question of statins and neuromuscular diseases?  If we
are correct, the neuro problems should be showing up quite soon now. 
though it may take the medical community another decade to make the
association.  I am reminded of hormone replaement therapy a mere 10
yrs ago--everyone I know was on it, including myself.  thanks, olsen
Subject: Re: statin drugs and interruption of coenzyme q10 pathway
From: pegallina-ga on 13 Oct 2004 08:13 PDT
 
My husband had been taking depakote, neurontin, zocor and atenolol for
years and was developing parkinson symptoms- freezing up, tremors,
loss of expression, choking, etc., etc. Doc added sinemet and there
was minimal relief of the symptoms.  We moved and started with a new
neuro who suggested stopping the depakote.  After a horrendous 2 weeks
of weaning from the depakote and getting him on tegretol he has been
improving steadily!  Now I'm going to investigate the zocor!

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