in this video I'll teach you everything that you need to know about purine Salvage this is the third and final video in the series of videos about purines and peridin a brief overview purine Salvage refers to the biochemical pathway that recycles purine bases into purine nucleotides simply put the body has to have a way to go backwards and recycle the purine bases back into the purine nucleotides so that purine Salvage and purine synthesis can operate seamlessly and the body can create all of the different molecules that it needs the starting point for purine Salvage is going to be guanine hypo xanthine or adenine so let's get started there on this slide you see the free bases guanine hypo zanthin and adenine and I've shown them here in green let's start with guanine and hypo zanthin because those two are much more important than adenine in terms of understanding them for the purposes of exams so guanine will get recycled back into the nucleotide GMP and hypo xanthine which again is a free base will get recycled back into the nucleotide imp and I've shown the nucleotides on this slide in blue the enzyme that recycles both the free based guanine as well as the freebased hypo xanthine is hgprt which stands for hypo xanthine guanine phosphor ribosy transferase just know it as hgprt so the first high yield point to know is that this is the key enzyme hgprt converts both guanine and hypo zanthin which are free bases into GMP and imp respectively which are nucleotides once you recycle back into GMP or imp G GMP and imp can each be turned into the nucleoside guanosine and inosine respectively so very very high yield and the most high yield part of this video to understand you're starting in puan Salvage with the free bases guanine and hypothe and you're converting them or recycling them if you will salvaging them which is why this is called purine Salvage back into GMP and imp the enzyme that converts guanine and hypothe into GMP and imp is hgprt so obviously because we're talking about one enzyme doing two different reactions that enzyme is extremely high yield as you'll see in just a few slides that enzyme is also very clinically relevant because if there's a problem with it we get a certain disease more on that in just a second now looking at the right side of this slide we also have the free base adenine adenine can combine with prpp which we've seen now in several videos and we will become the nucleotide the enzyme that converts adenine back into am to recycle it is aprt which stands for adenine phosphor rosil transferase so as you can see on this Slide the purpose or the goal of purine Salvage is to salvage meaning to break down and reutilize components of the free bases guanine hypo zanthin and adenine now let's take a look at the left hand side of this slide both guanine and hypo xanthine if they're not going to be used for recycling can be turned into xanthine and then once you have xanthine xanthine gets converted by xanthine oxidase into uric acid so something that's very high yeld to know for exams and extremely clinically relevant to know in real life is that there's a disease that happens if hgprt is knocked out and defective so if we knock out the enzyme hgprt which under normal circumstances would recycle guanine back to GMP and recycle hypo xanthine back to imp we cannot go in the direction of the purine Salvage pathway in other words those two now dotted curvy lines cannot occur you cannot go from gu from guanine to GMP nor can you go from hypo xanthine to imp because obviously the enzyme responsible for that Salvage is broken so as a result of an hgprt deficiency we are now shunted in the direction of xanthine so guanine instead of becoming salvaged into GMP will get converted to xanthine and likewise hypo xanthine instead of being salvaged into imp will be shunted and converted into xanthine the more xanthine you produce the more uric acid you produce because xanthine naturally gets converted to uric acid through an enzyme called xanthine oxidase so in other words if we knock out hgprt not only do we move in the wrong direction and cannot do purine Salvage but we increase our levels of uric acid and when we increase our levels of uric acid to the extent that you would increase it in the case of an HG PRT deficiency we get some clinical symptoms because all of that uric acid has to go somewhere in the body so the disease that I've just described to you is known as Les Nyan syndrome L Nyan syndrome is an hgprt defect so we cannot recycle guanine or hypothe and instead it shunts the biochemical pathway in the direction of uric acid so we have an extremely excessive amount of pathologic uric acid now this disease is xlink recessive and the symptoms that we see are intellectual disability self mutilation aggression sodium urate crystals in the urine and that's due to hyperuricemia so excess uric acid will become urinated out and will precipitate into sodium urate crystals gout because all of that uric acid has to go somewhere and it's going to end up in different joints and dystonia so if we think about this disease Les Nan syndrome is too much uric acid and you can think about this although it's somewhat incorrect to say it this way but you can think about this as excess uric acid in the brain causes intellectual disability aggression and self mutilation excess uric acid in the urine causes sodium urate crystals which appear orange and excess uric acid in the muscles and Joints causes gout and distonia I'm Taking Liberties by describing it that way but that's how you can think about this to help memorize the symptoms the treatment for Les nen syndrome is going to be Al alopurinol and if you can't use alopurinol then you would choose on the exam F fuat the reason that these are the treatments is because both alopurinol and fostat inhibit the enzyme xanthine oxidase which converts xanthine into uric acid so in the case of Les Nan syndrome if the hgprt enzyme is knocked out and the biochemistry is shunting in the direction of xanthine if you inhibit the enzyme that converts it into uric acid then you won't get a buildup of uric acid in the various parts of the body which are responsible for the debilitating symptoms of Le Ian syndrome the thing to keep in mind for the purposes of USMLE or comlex is that usually when they're going to go after this on an exam they're going to do it clinically they're going to describe the symptoms to you they might give you sodium urate as a buzzword something that you definitely want to be thinking about is the hyper uremia causing those sodium urate crystals because a lot of times what they'll do is they'll describe a very young baby or pediatric patient with this disease and they'll show you a picture of a diaper with some RNG looking substance in it and so if you see an image on your exam of a diaper with like an orange red spot in it stop what you're doing and pick Les Nyan syndrome because what they're showing you is sodium urate crystals that were urinated out into a diaper and because of the chemical appearance and composition of uric acid those sodium urate crystals appear orange so that's very very important but this video is everything that you need to know about purine Salvage very very high yield and clinically relevant of course is Les Nyan syndrome but understand the biochemistry understand the disease and please understand the treatment good luck