More on Hepatitis B

[Karl Fischer]

In article <3q8fad$ji6 at ixnews2.ix.netcom.com>, srussell at ix.netcom.com
(Sandra Russell) wrote:

> The similarity of the RTs suggests a 
> natural explanation for the recent disaster using a nucleoside analogue 
> on Hep B patients-- it nailed all their mitochondrial transcriptases, 
> and wiped out their livers.

If by transcriptase you mean the mitochondrial DNA polymerase (gamma
polymerase) then you are correct; the drug FIAU (fialuridine) showed very
pronounced mitochondrial toxicity. Oh, and it would appear that FIAU
toxicity was a cummulative effect.

  Mitochondrial toxicity has been the major 
> problem with nucleoside analogue HIV drugs, too, but oddly enough in 
> nerve and muscle, not liver.  Wonder why not? 

A person better versed in pharmacokinetics should probably answer this but
what the hey....one thing about the two tissues you mentioned is the high
demand for ATP. If one was to see an acute mitochondrial toxicity, it
would be most apparent in those cells/tissues which "work" their
mitochondria quite hard. 

 The lentiviruses use an 
> Mg dependent RT, but I know that type C retroviruses use an Mn dependent 
> one.  If mitrochondria are descendents of bacteria, I wonder if their 
> DNA replicase is Mn dependent, too, like their SOD is.  Anybody know? 

Hmmm...can't answer that one.
 
> Anybody know the metal dependence of the hepadnavirus DNA replicase?

For the duck hepatitis B virus polymerase there is a dependence on Mg for
full activity; use of Mn showed a 90% decrease in activity.

Cheers,

Karl

-- 
Karl Fischer
kfischer at gpu.srv.ualberta.ca
tyr-2 at bones.biochem.ualberta.ca