Are There Studies Showing How To Inhibit Glycolysis And Encouraging Oxidative Phosphorylation

[ecstatichamster]

I'd love to learn more about studies you may have found. Thank you.

 

[murdoc]

I thought glycolysis is the first step of aerobic respiration. It provides pyruvate for the citric acid cycle. So you do not want to stuck in glycolysis rather than inhibit it.

 

[ecstatichamster]

Glycolysis as an end point, is how Dr. Peat uses the term, resulting in pyruvate that is metabolized into lactic acid to generate ATP rather than proceeding though the Krebs cycle.

 

[Highserotonin90]

[QUOTE = "ecstatichamster, post: 463249, member: 3389"] La glicolisi come punto finale, è il modo in cui il Dr. Peat usa il termine, risultando in piruvato che viene metabolizzato in acido lattico per generare ATP piuttosto che procedere attraverso il ciclo di Krebs. [/CITAZIONE]

@ecstatichamster Can you clarify this point? why does pyruvate not enter Krebs correctly and produce lactate?

 

[Korven]

[QUOTE = "ecstatichamster, post: 463249, member: 3389"] La glicolisi come punto finale, è il modo in cui il Dr. Peat usa il termine, risultando in piruvato che viene metabolizzato in acido lattico per generare ATP piuttosto che procedere attraverso il ciclo di Krebs. [/CITAZIONE]

@ecstatichamster Can you clarify this point? why does pyruvate not enter Krebs correctly and produce lactate?

In order for pyruvate to enter TCA cycle/oxidative phosphorylation it needs to get converted to acetyl CoA through the pyruvate dehydrogenase complex.

There can be many reasons as to why pyruvate --> acetyl CoA conversion wouldn't work properly. Could be a lack any of the cofactors, mainly thiamine pyrophosphate (vitamin b1) and magnesium, a low NAD+/NADH ratio will also push pyruvate towards lactate instead of acetyl CoA.

 

[ecstatichamster]

In order for pyruvate to enter TCA cycle/oxidative phosphorylation it needs to get converted to acetyl CoA through the pyruvate dehydrogenase complex.

There can be many reasons as to why pyruvate --> acetyl CoA conversion wouldn't work properly. Could be a lack any of the cofactors, mainly thiamine pyrophosphate (vitamin b1) and magnesium, a low NAD+/NADH ratio will also push pyruvate towards lactate instead of acetyl CoA.

thank you.

 

[Korven]

thank you.

Also, PDH is under regulation by pyruvate dehydrogenase kinase (PDK) which inactivates one of the enzymes in PDH.

Haidut has talked about suppressing PDK as being therapeutic in different contexts for restoring energy metabolism, vitamin B1 seems to have this effect The Anti-cancer Chemical DCA May Treat Chronic Fatigue Syndrome (CFS)

 

[Highserotonin90]

@Korven @ecstatichamster

Guys it could be the turning point in my life ... I started at 5 years old and now I'm almost 30 I am still fighting this ordeal ... I have always claimed that the cause was metabolic but nobody has ever listened to me ... despite losing almost 18kg of lean mass ... numerous tests and unnecessary visits ...

I read the thread on the NAD + / NADH report and started to suspect that my glycolysis was in excess with a consequent accumulation of pyruvate ... (it does not enter krebs and mitochondria).

For a week I started taking small doses of Niacinamide with the main meals with big benefits right away ... 30-60mg.

As far as the B1 is concerned I have the form HCL ... I didn't notice big differences up to 300mg while at 600mg I felt too wired and the feeling is that it increased the NADH.

I have always kept magnesium between 200 and 500mg.

At the moment what is making a HUGE difference is niacinamide in small dosages.

I suspect that at least my case is genetic.

In summary what can I do to make my pyruvate enter Krebs correctly? Niacinamide, B1, Magnesium, Biotin, ALA?

Thanks guys work and immense help!

 

[Highserotonin90]

In order for pyruvate to enter TCA cycle/oxidative phosphorylation it needs to get converted to acetyl CoA through the pyruvate dehydrogenase complex.

There can be many reasons as to why pyruvate --> acetyl CoA conversion wouldn't work properly. Could be a lack any of the cofactors, mainly thiamine pyrophosphate (vitamin b1) and magnesium, a low NAD+/NADH ratio will also push pyruvate towards lactate instead of acetyl CoA.

Should I then buy thiamine pyrophosphate or continue with the HCL form?

 

[Highserotonin90]

Consider the age of onset ... 4-5 years I would say that my cause is 100% genetic ... I also forgot great benefits from Vitamin A 1200-1300mcg (probably a low dose too).

 

[Highserotonin90]

Also, PDH is under regulation by pyruvate dehydrogenase kinase (PDK) which inactivates one of the enzymes in PDH.

Haidut has talked about suppressing PDK as being therapeutic in different contexts for restoring energy metabolism, vitamin B1 seems to have this effect The Anti-cancer Chemical DCA May Treat Chronic Fatigue Syndrome (CFS)

So is it better to avoid high doses of biotin since they activate the enzyme responsible for PDK?

 

[LLight]

Betaine is a positive regulator of mitochondrial respiration. - PubMed - NCBI
"Mitochondrial electron transport chain (ETC) complexes generate the mitochondrial membrane potential, which is essential to produce cellular energy, ATP. Reduced mitochondrial respiration and energy status have been found in many human pathological conditions including aging, cancer, and neurodegenerative disease. In this study we investigated whether betaine directly targets mitochondria. We show that betaine treatment leads to an upregulation of mitochondrial respiration and cytochrome c oxidase activity in H2.35 cells, the proposed rate limiting enzyme of ETC in vivo. Following treatment, the mitochondrial membrane potential was increased and cellular energy levels were elevated."

 

[Highserotonin90]

[QUOTE = "LLight, post: 531225, membro: 8564"] [/ QUOTE]

Excellent news ... before I was referring to biotin and not betaine ... but it is still useful information!

 

[Korven]

Should I then buy thiamine pyrophosphate or continue with the HCL form?

Honestly I am not the best person to answer what form is best/most bioavailable.

Dr Lonsdale at hormonesmatter.com is probably the most knowledgeable (and experienced) person on earth when it comes to thiamine and its clinical significance, I believe he recommends TFFD + magnesium.

 

[Highserotonin90]

Honestly I am not the best person to answer what form is best/most bioavailable.

Dr Lonsdale at hormonesmatter.com is probably the most knowledgeable (and experienced) person on earth when it comes to thiamine and its clinical significance, I believe he recommends TFFD + magnesium.

Can you answer my other questions please? what could I do to facilitate the entry of the pyruvate correctly?

As I said at the moment only Niacinamide (60-120mg per day) and Vitamin A are helping me.

Is there a risk of slowing down methylation with too much niacinamide?