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Majin_Bae t1_ivs9cif wrote

Reply to comment by FedXFtw in In a first, doctors treat fatal genetic disease before birth by 29PiecesOfSilver

No one’s answered your question and I have a biology degree and work for DoorDash so I can explain. Basically enzymes and what they bind to (substrate) can be summed up with the lock and key model. Depending on what the enzyme catalyzes, enough substrate that correctly binds to the enzyme will basically take up all the locks so the left over faulty keys won’t enter. although everything should be taken case by case, we know that enzymes have a high affinity for substrates that they’re after. So if there are enough correct enzymes available, they will bind to the substrates more readily out competing the mutated enzymes, like a key that goes into a lock smoother.

In the case these mutated enzymes out compete the normal ones, then youd be right about worrying about what to do with the bad eggs.

Hope this helps.

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Killer7481 t1_ivsg30o wrote

> No one’s answered your question and I have a biology degree and work for DoorDash so I can explain.

real sadboi hours

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[deleted] t1_ivsmjpz wrote

I know a particle physicist that works in a supermarket. Specialise too much, and there's no jobs if you aren't top of your field.

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DootDootWootWoot t1_ivt2l1j wrote

Maybe he just prefers that life? ¯_(ツ)_/¯

I've found many specialists can often generalize if their livelihood depended on it.

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FedXFtw t1_ivs9vct wrote

Are there any real world cases, be it disorders or syndromes, or just a disease or illness, which cause faulty enzymes which are similar enough, or reactive enough, where their mere existence is harmful to your health? In which case you'd need to both block the production of these AND provide the body with the proper ones

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[deleted] t1_ivsbvbe wrote

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Zouden t1_ivu5mjs wrote

But that's a recessive disorder, meaning the presence of some mutated protein isn't sufficient to cause disease. I believe /u/FedXFtw is asking about diseases where even some faulty protein is sufficient to cause disease even if healthy proteins are present.

For that I would look at dominant disorders, like those involving structural proteins such as collagen. In Ehlers-Danlos syndrome, a mutation in one copy of a collagen gene is sufficient to weaken the collagen structures.

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[deleted] t1_iwb7df8 wrote

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Zouden t1_iwb8s6j wrote

All genes are inherited the same way.

The difference between a recessive or dominant disorder is down to the actual function of the protein encoded by the gene in question; this in turn determines whether a loss of one copy of a gene (remember we have two of each) is sufficient to cause a problem. In many cases, losing function of one gene isn't a big deal because we have the other as a backup. Only when you lose two does disease occur. We call that recessive.

With dominant mutations, losing one is enough to be problematic. This is common in genes that encode for structural proteins, where you need every bit to work correctly.

An interesting case is the sickle-cell mutation of the hemoglobin gene. One copy of the mutation confers resistance to malaria, but two copies causes sickle-cell anaemia. The malaria resistance is a dominant trait, while sickle-cell anaemia is recessive.

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[deleted] t1_iwcnjys wrote

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Zouden t1_iwcp13v wrote

Yes, being dominant or recessive doesn't always correlate with how deleterious the mutation is. I'm not sure what your question is exactly?

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hypergol t1_ivsegyu wrote

sure, there are plenty of diseases caused by gain of function (rather than loss of function) mutations. Parkinson’s disease is one: loss of the ASYN gene is pretty much fine, but mutations in the gene cause familial (early onset) Parkinson’s.

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DJ_Velveteen t1_ivspoqr wrote

Huntington's, I reckon. Although iirc Huntingtin (the defective protein that kills you) may not be an enzyme and I'm on a phone so it's not easy to check offhand

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SerialStateLineXer t1_ivsivf0 wrote

Diseases caused by mutations resulting in toxic gain of function exist. Huntington's disease and some forms of ALS, for example. Generally these are inherited in a dominant fashion, since you only need one copy producing toxic proteins to mess things up.

For toxic gain of function mutations, there are various technologies for silencing the expression of toxic genes currently in clinical trials. Most of them use complementary RNA strands that bind to mRNA, preventing it from being used to synthesize proteins. I don't think any of these are currently FDA approved, but there should be some within a few years.

(Edit: According to Wikipedia, there are actually four RNAi (RNA interference) drugs on the market already).

Conversely, loss-of-function mutations are generally inherited in a recessive fashion, since one copy of a gene will usually produce enough of a protein. I believe that there are a handful of loss-of-function diseases inherited in dominant fashion due to haploinsufficiency (where one good copy cannot produce sufficient quantities of a needed protein).

There's some evidence that c9orf72 hexanucleotide repeat expansions, the most common genetic cause of ALS and FTD, involves both haploinsufficiency and toxic gain of function. Basically, the mutant c9orf72 protein doesn't fold correctly, producing toxic aggregations, and then there isn't enough good c9orf72 protein to clean up the mess. It's inherited in dominant fashion.

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