in this video I'll teach you everything that you need to know about the arachadonic acid pathway as it pertains to USM Elite and comlex as a brief overview arachadonic acid is a precursor of bioactive lipid metabolites which are known as eosino ioso and these include things like prostaglandins lucrin and epoxy iosat trinic acid these ecosites are pro-inflammatory which means when the body is in a state of inflammation or when the body needs inflammation these substances trigger oxidative stress and stimulate the body's natural immune response therefore because eosines are considered pro-inflammatory you can intervene in the arachadonic acid Pathway to treat or manage inflammation so let's go through the pathway the first thing that happens is from the membrane phospho lipase A2 promotes the release of arachadonic acid arachadonic acid can take one of essentially two Pathways one it can either as shown in green be reincorporated back into the phospholipid membrane and so it's essentially recycled or two as shown in the blue pathway it can be enzymatically changed into various different Downstream active metabolites and that blue part is what this video is going to focus on today for the purposes of usan clex you essentially want to understand that arachidonic acid can be enzymatically changed into Downstream bioactive metabolites through one of two Pathways the pathway shown on the left is the Lipo oxygenase pathway or locks the pathway shown on the right is the cyc oxygenase pathway or Cox so arachadonic acid can either be recycled or it can go through locks or now let's just kind of sketch out the pathway and we'll point out important things as we go on the left hand side in the lipoxygenase pathway the enzyme is five lipoxygenase and that will convert arachadonic acid into something known as 5hp so in the locks pathway arachadonic acid is converted by five lipo oxygenase into 5 HP on the right hand side in the Cox pathway the enzymes Cox one and Cox 2 will convert arachadonic acid first into pgg2 and then into pgh2 now both pgg2 and pgh2 are considered cyclic Endo peroxides that's not really important to know for your exam but I'm pointing that out for completeness sake because it's from these cyclic Endo peroxides that other bioactive Downstream products are derived but you have to convert arachadonic acid into these substances first so at this point in time let's focus on the Cox pathway on the right hand side once we've generated pgh2 pgh2 can be converted into any of the following prostacyclin prostaglandins or thromboxanes and again as the over view of my video pointed out these are generally pro-inflammatory substances so you're going to have one or multiple of these produced in states of inflammation for pgh2 to be converted into prostacyclin as shown in blue you would use the enzyme prostacyclin synthes and in this case you would derive the product pgi2 for pgh2 to be converted into prostaglandins you would use the enzyme prostaglandin synthes and the various prostaglandins that could be produced would be pge1 pge2 or pgf2 and for pgh2 to be converted into thromboxanes you would use thromboxane synthes and the various potential products there include thromboxane A2 or txa2 and throm boxine B2 or txb2 now I've colorcoded this for your studying pleasure but just be aware that you first convert your arachidonic acid through Cox one and Cox 2 into your cyclic endo peroxides and then your cyclic Endo peroxides can be changed into prostacyclin prostaglandin or thromboxane now let's focus on the left-hand part of this slide going from arachadonic acid to 5 HP te as we touched on already the enzyme that does that is five lip oxygenase and then 5 HP can be converted through the same enzyme into lucot Trine A4 or lta4 just like we saw on the right hand part of the Cox pathway where you first need to form cyclic endoperoxides in order to get Downstream prostacyclin prostaglandins and thromboxanes in the locks pathway when you're trying to make lucot triin you first need to make lucot Trine a 4 and then from lucot Trine A4 you can either convert to your lucot Trine C4 D4 or E4 which are shown in brown using the enzyme ltc4 synthes or you can convert lucot Trine A4 as shown in purple to lucot Trine B4 using the enzyme lta4 hydras so the important thing to keep in mind for the purposes of exams is that in the locks pathway all of the lucot triin are derived from lucot Trine A4 and in the Cox pathway all of your prostacyclin prostaglandins and thromboxanes are derived from pgh2 which again is a cyclic Endo peroxide now all of these products the things shown in brown purple blue green and orange have different functions and on your exam you might need to know what those functions are because different substances are inhibited by different drugs so you need to know one the physiological function of these bioactive products and then two what medications can inhibit them so let's look at this chart on the leftand side we have all of our different bioactive products of the arachadonic acid pathway lucot Trine B4 lucot Trine C4 lucot Trine D4 and lucot Trine E4 then we have our pgi2 which is a process cycl we've got our three prostaglandins pge1 pge2 and pgf2 and then we have our thromboxane thromboxane A2 or TX A2 now I've listed out the functions for you the most important thing on this slide is to know that lucot Trine B4 its function is neutrophil chemotaxis so it is responsible for essentially ushering the nutrifil to the proper site of inflammation pneumonic here is that LTB B for buses it buses neutrophils to where they need to go that's really important because a lot of times on exams they're going to test if you know which lucot Trine is involved in nutrifil chemotaxis so in your head all you need to remember is my pneumonic and say oh the neutr bus B for bus lucot Trine B4 it buses the neutrophils all of the other lucot triin which is C4 d 4 and E4 they are involved in increasing bronchial tone so it may not surprise you to hear that in the treatment of respiratory illness in particular asthma you can give medications that inhibit these lucot triin because you want to decrease the bronchial tone and my pneumonic for memorizing this is CDE bronchial Tony CDE bronchial Tony which helps me remember that CDE increases bronchial Tony and that's how it's always stuck in my brain pgi2 decreases platelet aggregation and causes vasod dilation so PGI for platelet Gathering inhibitor it decreases platelet aggregation pge1 is a vasodilator and both pge2 and pgf2 increase uterine tone and so just like I had that kind of rhyming pneumonic above for the lucot triin for pge2 and pgf2 what I say is ef2 uterine tone 2 ef2 uterine tone 2 so E and F and of course it's E2 and F2 uterine tone 2 it increases uterine tone and then lastly txa2 thromboxane A2 this increases platelet aggregation and it's a Vaso constrictor and you want to know that it increases platelet aggregation so txa for thrombocytosis extra activator which is a ridiculous way of remembering that it causes thrombocytosis which means lots of platelets and then in my head I see these platelets aggregating together so these are the functions of your various products of the arachadonic acid pathway if you're watching this video and you're like dude I'm not going to memorize this your pneumonics suck then what you probably want to take from this if you're going to pull just one thing out of here is that lucot Trine B4 buses your nutrifil B for buses it's involved in nutrifil chemot taxis that's probably the best return on investment on this slide so here we are in our pathway the last thing that you need to know for usan complex is that in the arachadonic acid pathway various different medications essentially serve as anti-inflammatories which is to say that different medications can help with various states of inflammation or various PA pathological States because they inhibit different parts of this pathway and have differing effects on inflammation so I've colorcoded everything but just to draw your attention to what's on the slide glucocorticoids which are shown in green inhibit phospholipase A2 so they they sort of act on the most Upstream part of this pathway which is why uh glucocorticoids tend to be really fantastic anti-inflammatory agents not just because of this mechanism but certainly because of this mechanism M they inhibit phospholipase A2 shown in red we can see that nids will inhibit Cox one but interestingly celic coxib will selectively inhibit Cox 2 which is important because nids have pretty nasty gastrointestinal side effects and by targeting specifically Cox 2 celic coxib can spare an individual taking an nid or taking the celic coxib from some of those GI side effects shown in blue we see that epoprostenol inhibits pgi2 carboprost inhibits pgf2 dinoprostone inhibits pge2 and alprostadil inhibits P1 what you'll notice is in all of these medication names you see Prost Prost so if you're taking your exam and you have to take a guess as to what these things things inhibit it's either going to be a prostag glandon or a prostacyclin because they all have Prost in the name probably not worth memorizing it's really not a super high yield concept but I'll just leave it as if you see a medication with Prost it's inhibiting either a prostag glandon or a prostacyclin shown in that gold color on the bottom left hand part of the slide Mont lucast and Zafir lucast are going to inhibit your lucot triin and just like we saw with The Prost agents these have Luke in the name so they're going to inhibit Luke OT triin specifically they're going to inhibit the lucot triin that increase bronchial tone because in your various respiratory pathologies you want to decrease respiratory tone so you're going to inhibit the Lukes that increase bronchial tone and then lastly shown in Orange zylon is going to inhibit five lipoxygenase and again we have l in the name so it's inhibiting an enzyme that's responsible for the creation of line A4 the way that you can memorize this is that the one that begins with Z you're going to inhibit the Luke that begins with a so I always thought A to Z lucot Trine A4 to Z for zylon A to Z A4 is inhibited by zylon and specifically it's inhibiting the enzyme that produces lucco trying A4 so there's a lot of information in this video you need to know your pathway you need to know the physiological function of your lucrin prostacyclin prostaglandins and thromboxanes you need to know the medications and their mechanisms that you see on this slide and remember if you're like nope not going to do it I'm just not going to do it just remember lucot Trine B4 is involved in nutrifil chemotaxis good luck