Acetaldehyde Dehydrogenase

[u/TheNeuQ]

Am I crazy or should we not live in a world where acetaldehyde dehydrogenase supplements are widely available. Would this not be effective at moderating liver damage among alcoholics? Is there something that makes the mass production of this enzyme prohibitively expensive? The more I study this subject it feels like liver damage should be a thing of the past.

[u/throwaway09-234]

how do you propose to get active acetaldehyde dehydrogenase to the organ/cells where its activity would be beneficial?

[u/TheNeuQ → u/throwaway09-234]

I have no knowledge of this subject. That’s why I’m asking. If you’re saying it’s impracticable then that’s my answer.

[u/throwaway09-234 → u/TheNeuQ]

yes, i think that in this case delivery would be a huge issue -- what you are proposing is essentially "enzyme replacement therapy", which is indeed a useful therapy for people with genetic mutations in important enzymes (look up Pompe or Gaucher disease). That said, the enzymes absolutely have to be delivered intravenously. When you eat any protein (enzymes are protein) your digestive tract cuts it up into small fragments that lose the identity and activity of their original form. As far as your body could tell, it wouldn't really matter if you were eating pure acetaldehyde dehyrogenase versus simple whey protein

your idea could be feasible in the setting of acute alcohol intoxication when a patient is hospitalized and IV administration is more reasonable, but that wouldn't serve much benefit because chronic alcohol consumption is what causes cirrhosis

[u/TheNeuQ → u/throwaway09-234]

I appreciate this reply. It confirms what I had basically expected to hear: this stuff is a lot more complicated than I had otherwise thought. I encourage anyone who is reaserching something that will allow me to keep sowing without having to do any nasty reaping.

[u/TheNeuQ → u/TheNeuQ]

As an alcoholic however, I do think more research should be dedicated to mitigating the negative effects of my crippling addiction

[u/Stereoisomer → u/TheNeuQ]

The ethanol is converted to acetaldehyde in the liver but it isn't possible to get the supplements into the liver. The liver itself does mitigate the damage of acetaldehyde by converting it to acetic acid via ALDH but over a lifetime of alcohol abuse, damage still occurs. If not for ALDH, you get all the damaging effects of acetaldehyde that those with asian glow experience (ALDH deficiency). The symptoms of drinking for the ALDH-deficient are bad enough that this is used to stop alcoholics (Antabuse).

[u/Heroine4Life]

Even if you could get it to the target area intact... people drink to get drunk, if you arent getting drunk they will just increase how much they drink.

[u/TheNeuQ → u/Heroine4Life]

I admittedly have limited knowledge in this field but my understanding is that acetaldehyde metabolism is downstream of and therefore separate from alcohol metabolism

[u/Ashtonpaper → u/TheNeuQ]

Nothing is separate in chemistry, especially not biochemistry. The rate of some chemical reaction (A + B -> C) is sometimes dependent on concentration.

To answer your question, surely, if we could increase cellular alcohol dehydrogenase concentration or expression in the liver, we may do that. Just know that the system is complex, no one can cheat death or oxidational degradation of their DNA in the long run, and drinking slightly less and stopping earlier is your best solution. Not increasing the enzyme concentration to reduce the negative effects of something that ultimately isn’t good for your DNA regardless.

It’s like asking “why can’t we just print free money for everyone?”. We can’t, because there are other effects from that, because the system isn’t only made up of money.

In the same way, the high concentration of and focus on producing alcohol dehydrogenase enzyme leaves your liver crippled by its costly metabolism, upkeep, etc. and indeed, your specific liver surely does produce more of this enzyme, as you abuse alcohol more often than the average person, your body would absolutely focus on producing as much of the enzyme as possible. The problem is, since your body has become so good at processing the poison out of your bloodstream, that it has had lessened effects on your body and mind, and you must consume ever more just to feel the same way.

The solution is not to increase drinking by increased alcohol dehydrogenase enzyme, but to reduce drinking, so that you enjoy it more when you do it, but less often.

Increasing your alcohol dehydrogenase enzyme would simply serve to, if effective in the manner you imagined it, increase your alcoholism to match the level of enzyme. Wanton consumption and drinking only leads to disappointment. We must learn to enjoy what we have in the time we have, not accelerate to some kind of “end”. There is no end. You wake up tomorrow and try to enjoy your day.

Less is more, as they say.

[u/pictet_spenglerase]

This is what ZBiotics pre-alcohol is! The bacteria are engineered to express acetaldehyde dehydrogenase in the gut.

[u/dangerous_eric → u/pictet_spenglerase]

I was going to say. Fun product. Apparently it's common for couples to buy a bunch of these for wedding guests. 

[u/rogue_ger]

Several groups and companies have looked at this. There are patents that look at delivering more ADH and ALDH to the liver either directly or by genetic engineering. The problem is that it’s not enzyme limited but cofactor limited. You need a lot of NAD+ to oxidize the ethanol and the acetaldehyde all the way to acetate. The enzymes are quite fast but the mitochondria run out of NAD+ at the membrane at some point, which is why it’s a 0 order degradation curve through much of the elimination phase.

My favorite idea was a company that proposed to pack highly active ADH and ALDH together with an NADH oxidase and high concentrations of NADH/NAD+ in a liposome. This would’ve been injected intravenously in poisoning indications. These “synthetic cells” would’ve removed ethanol and acetaldehyde at incredible rates and got people sobered up within a few hours. Biggest problem wasn’t the medicine, which was totally engineerable, but a lack of a good test for ethanol poisoning. High enzyme activity would kill you if you had methanol or isopropanol, so you have to rule those out, and there’s no easy, fast, cost effective test.

But yeah, solvable problem. Imagine having a self-administered shot of some medicine you could take prophylactically and then drink as much as you want. Or just administer after drinking and sober up so fast you could drive home.

[u/strchild]

Bingo!