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how can we say that point mutations alter synthesis of essential amino acids? - (Nov/04/2012 )

Hi there!

I am preparing for my viva about " point mutations in the BCR-ABL kinase domain of chronic myeloid leukemia (CML) patients"

I need some help about:

A common point mutation found in CML is we know that our body can't synthesize essential amino acids. Where M (methionine) and V (valine) both are essential amino acids...

The question is that how can we claim that the normal codon was coding for "methionine" and after a mutation it started coding for "valine"? although both are essential amino acids....hesis

Do we write "M244V" just to represent the nucleotide altered behind ...or an actual change in amino acid synthesis?


-de ifz-

"M244V" represent both the nucleotide altered and actual change in amino acid synthesis.
Three dimensional structure prediction may give some clue. Note whether mutation is in functional region of protein or do it influence three dimensional structure overall.


but my concern is that when we say that our body cant produce essentil amino acids..then how we are talking about methionine alterations???

-de ifz-

Just to clarify a few things..

Are you aware that genetic code ancodes the amino acid in a protein chain, that is taken from the pool of amino acids already present in a cell? The availability of the amino acids is not important for differences between normal and mutated protein. It's just there, methionine, valine, whatever. Essential only means body can't synthetise them and must take them from food, that's all. Unless there is serious starving, this doesn't change, and if there is one, all protein synthesis as whole is seriously affected. But probably before that, person would already die.

Now the mutation happens in DNA and changes the code, so that insted of methionine, valine is added, as the code says. There is bunch ov valines and methionines waiting, but only valine now gets a ticket.
Change in the amino acid sequence makes a different protein that has an altered function, in this case a mutation altering a kinase sensitivity to its inhibitor, that is used as a treatment for CML, so meaning worse prognosis for the patient.

Just please tell me you already knew that and just I either didn't understand the question or you wasn't clear enough in asking it... otherwise I would have to live with a finding that people exist, who are obviously supposed to have an exam from a Bcr-Abl mutations and probably CML pathology and they don't have a clue about how proteins work. Please, I desperately hope you'll prove me wrong..


Thankyou for the explanation about proteins. I appriciate that.
I am aware of this basic concept, its not a new thing to me.

To simplify my question please tell
"Do our body synthesize essential amino acids in a very less amount?"
rest I will interpret my confusion.

-de ifz-

There are amino acid that we can't synthethise at all, and those that we can, but may be not enought always.

But I still don't get why are you asking this regarding BCR-ABL and M244V. This mutation does not alter any methabolic pathway (it's a kinase, a signaling molecule) connected to amino acid synthesis or anything.

There is difference between protein synthesis - connecting the already present complete amino acids in cell together by peptide bond - and between amino acid synthesis - synthesis of the building blocks alone from some simple chemical structures (plus the fact that some bulding blocks you can't syntetise and need to get from food).

It's like you want to build houses from LEGO bricks, you have plan for a house and just add bricks together to build it. You need the free bricks pool, luckily you have a small factory, that can make some of them by pouring melted plastics into matrice, but some special bricks you can't make and you must get them regulary from a supplier. But that thing usually works fine.
If you have a mutation, it means a change in plan, you just use other brick than the original. That's all, it has nothing to do with the brick factory.

It's still obvious that there are still some concepts you are not aware of, since you wouldn't ask this way.. M244V by the way is a notation of a change of amino acid Methionine on the codon number 244 to Valine. But this protein change has to have it's origin in the DNA. This amino acid change is usually caused by single nucleotide substitution c.730A>G of guanine for adenine at possition of 730 of coding sequence.