Skip to content


  • by

In this video, I have talked about Drugs and Disease related to Purine Metabolism like 6-MP and Gout.

Hello guys welcome back to my channel anytime medicine and today we are going to talk about pure metabolism associated drugs and disease in my last video we have seen that purine metabolism and its three parts like synthesis salvaging and degradation today we are going to see drugs and disease that are related to each of those parts the first part is the purine

Synthesis and right limiting step for purine synthesis is impdh which converts the imp into the xmp which is synthesizing monophosphate with the help of nad plus and h2o you can see the imp and xmp structure below that is converting the imp into the xmp only difference is the one added oxygen into the xmp structure further we talk about red labeling step the xmp

Will convert into gmp with help of glutamine so ipdh is a rate limiting step for gmp synthesis therefore regulatory step for dna synthesis if we don’t have enough guanine then we cannot make the dna the first drug we are going to talk about is ribavirin which is antiviral drug which inhibits the impdh so it will block the conversation of gmp from imp and that will

Inhibit the synthesis of guanine nucleotides which are purines and there will be less period for virus to replicate themselves in the host’s body so that’s how we can slow down the infection of certain viruses the second drug we are going to talk about is mycophanolate and which is immunosuppressant t-cells and b-cells are very important for the immune response

In the body sometimes t-cells and b-cells override the immune system and will create the ombro-immune diseases mycophyllate inhibits the impdh in white cells so there will be less guanine in t cells and pieces to replicate therefore less these and b cells immune response and immune system will be suppressed it is used in organ transplant like kidney transplant

It will prevent the recipient’s immune system to attack transplanted organ the second part is purine salvage in specific hypoxanthine and guanine hypoxanthine and guanine will convert back into imp and gmp respectively interacting with the prpp an enzyme called hgprt which is hypoxanthine born in phosphorus ribosyltransferase yes you can see the reaction that

Hypogenetic and guanine is interacting with the prpp and hgprt and making imp and gmp the other drugs we are going to see are 6 mp and exotherm the first one is 6 mp that is stands for 6 mercaptopurin is a chemotherapy agent that mimics the structure of hypoxanthine and guanine and competes for enzyme hg prt because they have similar structures on your right

You can see the 6mp structure it has sulfur in it and on your left you can see the hyposentine structure that is have oxygen in it the 6mp will react to prpp and hdprt and will make theo inocenic acid and this theocenic acid will stops the whole salvaging process in this inhibits the multiple steps of these synthesis of urine synthesis this will decrease the

Production of imp amp and gmp and it is used as treatment for certain cancers like acute lymphocytic leukemia chronic myeloid leukemia crohn’s disease and ulcerative colitis the second is essa theoprine is also an immunosuppressant which will metabolize into the 6mp and the same series of reaction will occur and will decrease the production of imp amp and gmb

Also it is used in organ transplantation rheumatoid arthritis and inflammatory bowel diseases the third part of purine synthesis is purine breakdown fearing breakdowns in the uric acid and will be excited from the body the hypoxanthine and guanine will convert into the xanthine with the help of enzyme called xanthine oxidase and guanis like we have talked about

In my previous video further to it now xanthin will become uric acid with the help of xanthine oxidase xanthine oxidase is a very important enzyme for the purine breakdown if you don’t have vintage oxidase we can develop certain diseases that we’re going to talk about in this video later on in case of 49 adenine will have to convert back into the nucleotide and

Then breakdown will occur adenine will convert into the amp with the enzyme of aprt which stands for 1889 phosphoribosyl transferase then amp will convert into the adenosine and adenosine will convert into the ionosine with the enzyme of inosin d aminos ionosine will convert into the hypoxanthine with the enzyme of purine nucleotide phosphorylase now we’ll see

Adenosine deaminase deficiency which is ada deficiency ada required for degradation of adenosine and deoxy adenosine which is datp so if we have less ada then we will have more datp so there will be decreased ribonucleotide reductase activity too if we have more datp that will give negative feedback to this enzyme and that will decrease itself decrease itself

Too that will lead to lympho toxicity and this is also major cause of scid which is severe combined immunodeficiency the other disease is gout occurs when there is excess uric acid in plasma there will be crystal deposition in joints and that will lead to pain swelling and redness can occur when there will be under exhalation of uric acid patient with diuretics

Like furosemide or can occur from over production of uric acid via purine pathway patients which have trauma and with have high doses of chemotherapy will have lots of preparing into the plasma because while trauma we lose so much purine in plasma and chemotherapy there is inhibition of purine synthesis so we will have lots of purine in plasma and they will break

Down them into the uric acid further if we if we consume high amount of puritans food like meat and seafood we can most likely to develop gout yellow purinole is a drug which help in gout which inhibits sensing oxidized we have to be caution us in using this drug while using with 6 mp and exartheoprine because they metabolize by sensing oxidase and make theo

Uric acid which is inactive form of uric acid so there will be high level of 6 mp and exothermic they may boost effect of 6 mp but they can cause toxicity too this combination can use intentionally in some cancer and cancer patients that will boost the effect of 6 mpn azathioprine so this is the common location for gout and you can see the crystallization of uric

Acid at the joint in a food and you can also see the redness of the area the last disorder we are going to talk about is less nihan syndrome which is x-linked disorder occurs only in boys in which children are born with absence of hgprt in absence of hdprt we cannot convert aposentin and guanine into the xmp and gmp so there will be more hypoxanthine in guanine

And there is also excess of uric acid production because of the excess hypoxanthine and one and they will go to if we didn’t break down pathway and will create more uric acid and this is called juvenile gout 2 because occurs only in children so excess the no appearing synthesis will ramp up because not able to salvage purine so there will be excess prpp and imp

There will be neurological impairment and this mechanism is unclear how the neurological impairment occurs the neurological impairment are hypotonia and chorea the classic feature of the neurological impairment is self-mutilating behavior like self-biting and self-scratching sadly there is no treatment available for this syndrome here you can see the pictures of

Cell biting fingers and lips this is the classic pictures of self biting of fingers and self biting of lips thank you everyone for watching this video subscribe my channel share it to your friends and see you on the next

Transcribed from video
PURINE METABOLISM – What you need to know ? | PART-2 | BIOCHEMISTRY | ANYTIME MEDICINE By Dr. Akash Mangukiya