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Genetics lecture 2
Now for This lecture, I will continue what I started last time, SO I will
continue talking bout or the general objects for today's lecture:
NOW, let us see this slide (#16), which represents part of the
degradation of purine, so there is AMP and GMP, through this pathway
they will end up with uric acid…
So>> taking a lot of purines will result in a lot of uric acid production and
production of uric acid above normal concentration is considered as
disorder and that disorder in medicine called Gout.
How uric acid in the brain will damage it? (Only Concentrations >>
above the normal will lead to the Lesch-Nyhan syndrome, which is X
linked inherited disease)…. (Slide # 19)
?? One student asked a question but I couldn't hear the question but the
Doctor answered: because the compound (Allopurinol) is not the proper
substrate of these enzymes, it could be a substrate analogy but not the
proper substrate, so these enzymes in the presence of allopurinol will be
active, but when it is converted to Alloxanthine, that will inhibit these
enzymes completely and thus uric acid production will stop..
Another question which also I couldn’t hear but the doctor’s answer ??
was: Allopurinol must be converted to Alloxanthine to be working on
the treatment of Gout but Allopurinol itself can’t be harmful on the
body, The treatment requires low concentrations of Uric acid in the
.body
In slide # 22, we can see that Uric acid and some other compounds ••
.are good antioxidants such as bilirubin, glutathione and ascorbic acid
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
PYRIMIDINE METABOLISM
In slide # 23, you can see the main objectives that you have to
understand after reading this lecture from our LOVELY BOOK!!
And anyone who doesn’t understand, just come and ask or go to the
book and find the answer!! So you have to answer these questions and if
you do it easily, there will be no problem for you from this course.
?Q: Any one wants to name some pyrimidine that we will talk about
.After asking six students who couldn’t know, finally Uracil comes up
The next slide (# 25) shows us the differences between the two types of
;carbamoyl phosphate synthetase type 1 and type 2
.Quick note!! The CTP, CDP and the CMP are nucleotides
Another student asked: where is the dTMP in this pathway? And the ??
doctor answered: the dTMP isn't emphasizing in this pathway, it has a
specific pathway we will mention it in a moment…..
Q(A very very good question): from where we got this? Every thing we
know is that we got UMP and UDP and UTP and somehow CTP but
??dUMP has been seen for the 1st time, from where we got it
SO, the enzyme that will work, converts the ribonucleotides to deoxy
ribonucleotides, and this enzyme is very very important, because the
deficiency or inhibition of it will stop the whole life!! Because it will not
have deoxy pyrimidines or purines to synthesize DNA. Of course if we
.have that enzyme deficient or inhibited
This is not talk about the tissue, it only talk about the regulation and look
at it!! It is highly complicated because it is very important and it must be
under regulation because it is a crucial enzyme to synthesis,, why??
Because it converts ribonucleic acid to deoxyribonucleic phosphor DNA
synthesis and gene synthesis and DNA replication and all these
.processes that we need, vital processes
The doctor wants us to think about the correlation of this enzyme and <
malignancy and cancer cells while he is explaining the regulation of the
>enzyme
Now, the substrates for this enzyme (in slide #32) are:
These are the positive allosteric effectors for this enzyme for each
substrate….. Also in slide # 32.
SO, ATP is a positive effector for the diphosphate reductase, for each
substrate; for the CDP and UDP substrates,, and dGTP is a positive
effector, for ADP substrate and finally dTTP for GDP substrate, And
these came by experiments.
These are the medical effectors (negative allosteric effectors) and if you
notice, in all of these substrates for this enzyme, dATP is based, so high
amounts of dATP is toxic.
So, high amounts of dATP is toxic to the cell and you must prevent high
amounts of dATP above normal concentration, there is a disease, in
which dATP is highly accumulated.
Slide # 33, the doctor will leave it to us to read, but he said about
it:
It's very easy, I've already mentioned about it, I don’t need it by
explicitly, I’ve already mentioned that but not in clear! so I want
you to read it and figure out if you understood the steps of
synthesis of purines and pyrimidines, you must be able to
differentiate between the 2 pathways...
Synthetic sequence:
In the case of purine, N- glycosidic bonds and then ring assembly and
closure.
?? Does that make sense to you?!! The things are opposite as one of the
students said….
SO>> firstly we have the sugar and then make the N- glycosidic bond in
purines and then build on the N which is bonded to the sugar.
If the cell was degraded, then the DNA and RNA will be degraded
and the enzymes that will degrade them are: DNase and RNase.
They will form TMP and then deoxythymidine OR UMP, dUMP,
CMP and dCMP then dephosphorylation to produce
deoxycytidine, cytidine, uridine and deoxyuridine.
BUT:
One from DNA and one from RNA, further dephosphorylation for them
we come up with deoxyuridine and then they remove the sugar and
return back to nitrogen bases (Thymine, uracil, cytosine) and then
further metabolism to these nitrogen bases (thymine and uracil) till we
reach to the succinyl coA and acetyl coA.
Uric acid
Before talking about this, I will talk about the correlation between
ribonucleotide diphosphate reductase and cancer….
Q: Did you figure out any correlation or connection? Could you barn
cancer cells by inhibiting this enzyme?
Slides # 39, 40 and 41 shows the structures of the compounds that are
mentioned before, just to look at them not to memorize them.
Still to talk about bubble boy syndrome or adenosine deaminase
deficiency in the next lecture……………………………..
GOOD LUCK