PMID 9749577 Understanding cell death in Parkinsons Disease
Increased Fe3+ Ferric iron, inhibited or decreased complex I, decreased
GSH, dying neuromelanin, decreased dopamine.
Fe3+ combines with dopamine increasing lipid peroxidation that is combated
by GSH.
Fe3+ likes neuromelanin. The Lipid peroxidation kills the neuromelanin.
Tellurium and manganese increase Fe3+, inhibit complex I, decrease GSH, and
destroy neuromelanin.
Manganese Toxicity causes Parkinsons but no loss of dopamine.
N-Methyl decreases available dopamine by turning it into (R)Salsolinol.
N-Methyl Tellurium causes Parkinsons because it meets all the criteria of
+Fe3+, -Complex I,-GSH,-Neuromelanin,-dopamine.
Ferrochelatase :
Manganese prevents Fe3+ iron from getting into the inner membrane where it
can be broken down by ferrochelatase.
Tellurium can take the place of sulphur, but is unlike sulphur, and cannot
turn Fe3+ ferric iron to Fe2+ ferrous iron, or the 2Fe-2S iron-sulphur
cluster of ferrochelatase.
MPTP - N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine:
1. N-Methyl would inhibit dopamine.
2. PMID 10501216 Inhibitors of mitochondrial respiration, iron II or Fe2+.
MPP is an inhibitor of complex I.
PYRIDINE-PYRROLE RING-PORYPHYRIN-FERROCHELATASE
Pyridine -obtained from the distillation of bone oil or coal tar. Binds
with catecholamines.
Pyrrole ring - found in many important biological pigments and structures
that involve an activated metal ion, like hem. Binds with catacholamines
like adrenaline, noradrenaline, and dopamine.
Poryphyrin - are pigments that chelate metals and are constitutes of
haemoglobin.(hem)
3. PMID 10561552 Human Ferrochelatase catalyzes the terminal step in the
heme biosynthesis pathway, the insertion of ferrous iron (Fe2+) into
protoporphyrin IX to form protoheme IX. (Protoporphyrin is a form of
poryphrin.)
So MPTP exposure lets the Fe3+ iron in the inner membrane, unlike
Manganese. MPTP lets ferrochelatase do it's job just fine, unlike
tellurium. But Ferrochelatase has no poryphrin to hand off the extra iron
to, so there remains lots of extra Fe3+.
The Fe3+ combines with dopamine causing increased lipid peroxidation that
destroys the neuromelanin cells.
The GSH tries to combat the extra lipid peroxidation and becomes decreased.
4. MPTP Toxicity, N-Methyl-Tellurium Toxicity, and Manganese Toxicity, all
cause and increase in Fe3+, decreased complex I, decreased GSH, decreased
neuromelanin. N-Methyl is common to MPTP and N-Methyl Tellurium and
decreases dopamine.
It looks like they all cause Parkinsons Disease.
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