welcome back to dirty medicines dirty biochemistry series this video is on the disorders of galactose metabolism if I can pause for a second and just lay out kind of how we're going to go through this video we're going to start by outlining the normal biochemistry so I'm going to give you the pathway about how we start with lactose and convert it into different sugars and work our way through the pathway of galactose metabolism along the way I'll show you what three diseases will manifest if we knock out certain enzymes that is to say if we have certain enzymatic deficiencies as I go through these diseases I'll give you my awesome dirty medicine mnemonics to help you remember the hi old findings that you'll be asked to know on test day when you sit for us Emily or comlex so let's begin by talking about lactose which is our starting material lactose can be converted into both glucose and galactose the enzyme that converts lactose into galactose is lactase another way of saying this is that the enzyme lactase breaks down lactose now think about the name you've probably heard about lactose intolerance before and you're also probably aware that this is due to a problem with the lactase enzyme but if you look at the name lactase it's telling you that it's acing or breaking down lack'd or lactose so that's where the name comes from so again lactose is converted into galactose by lactase now everything you see here shown in the gray box is occurring at the brush border of the small intestine we'll come back at the end of this video and talk about lactose intolerance because of the three diseases of galactose metabolism it's the lowest yield next galactose can be converted also into one of two different products one is galactose 1-phosphate and the other is Galacta tall now you need to know both of the enzymes that convert galactose into these two different products the enzyme that converts galactose into Galacta tall is aldose reductase the enzyme that converts galactose into galactose 1-phosphate is galacto kinase now just as an aside sort of a big picture high-yield way of remembering some biochemistry whenever you see an enzyme that ends in kinase it means it's just putting a phosphate group on whatever the reactant is so in this case you start with galactose and it gets a phosphate in the one position and that's why the enzyme is galacto kinase because it's kinase Anor sticking a phosphate on galactose this also helps explain why the product is galactose 1-phosphate because it has one phosphate stuck onto it by galacto kinase so keep that in mind if you're ever struggling with enzyme names reactants and products now galactose 1-phosphate can be converted into glucose 1-phosphate by the enzyme galacto kinase one phosphate your it'll trance race in this step you need UDP glucose to be converted into UDP galactose as a cofactor now this step is extremely extremely important to understand and it's very high yield we'll talk about it in a little bit about knocking out this enzyme and what disease you get if that happens now once you have glucose 1-phosphate you should be a little bit familiar with this product glucose 1-phosphate has a lot of downstream options it can enter glycolysis it could enter glycol Genesis it can be used in a ver in a variety of biochemical pathways so keeping with our theme that we've seen throughout the dirty biochemistry series different reactions are generating different products which can be used by other biochemical pathways so this is the main pathway of galactose metabolism and you need to know the enzymes shown in red you also need to know the cofactor shown in green now let's talk about what happens if you have certain enzyme deficiencies the first disease that we'll talk about is what you get if you knock out galacto kinase so shown in this large blue X we have an enzyme deficiency of galacto kinase now think about this by looking at our pathway if you don't have galacto kinase then you cannot convert galactose into galactose 1-phosphate so you can't do the blue dotted line instead this will be shunted to the blue thick line so galactose will be converted into Galacta tall by aldose reductase so by simply knocking out galacto kinase we have a preference to divert galactose into galactose all this disease is aptly named a galacto kinase deficiency so again what do you have here you have a decrease of the enzyme galacto kinase you have a decrease of the product galacto kinase one phosphate because you cannot convert the reactant into the product instead you have an increase of Galacta tall because the pathway gets shunted in preference of converting galacto kinase into Galacta tall so these are the findings that you need to be familiar with for a galacto kinase deficiency but there are a lot of clinical findings and other high-yield features that you could be required to know on USMLE or complex and that's what we're going to talk about now the other things that you should know about a galacto kinase deficiency are that you'll see galactosemia which means galactose in the blood right amia means blood so galactose emia galactose in the blood galactose urea which urea means urine so galactose in the urine so galactose in the blood and the urine because we have a lot of galactose that's accumulating since we cannot use galacto kinase you'll have abnormal eye tracking i'll come back to this in just a second but you're gonna see a lot of visual difficulties when you have an accumulation of galactose all lack of the development of a social smile this is an autosomal recessive disease and you'll see infantile cataracts now overall galacto kinase deficiency is really not a severe disease so you see infantile cataracts that aren't that bad and you see abnormal eye tracking when you have an accumulation of a substance like Galacta tall that substance actually gets trapped in the lens of the eye and when that happens you get the cataracts and you get abnormal eye tracking so how do you remember all of these high heel findings well you should remember this by remembering galacto kinase deficiency gee al AC G for galactosemia and Galactus urea because that galactic galactose is accumulating in the blood and accumulating in the urine a for abnormal eye tracking because there's an increase in Galacta tall which is being trapped in the eye L for lack of a social smile during development a for autosomal recessive disease and C for infantile cataracts or just cataracts so that's galacto kinase deficiency and it's really not as bad as the next disease that we're going to talk about so again this is a galacto kinase deficiency when you knockout galacto kinase now let's talk about the more severe form of a galacto kinase problem and that's if we actually knock out the next enzyme in the pathway we knock out galacto kinase one phosphate your it'll transfer ace so this is a really severe disease much more severe than the galacto kinase deficiency and the reason is that because this enzyme is processing a lot more of the galactose load in the body so if you knock this one out the symptoms are going to be way more severe and you're gonna get a greater accumulation of products in the body and it's that accumulation of products that isn't normally there that causes all of the symptoms so look at our pathway if we knock out galacto kinase one phosphate your Riddle trance race then we can't do the two blue dotted lines we cannot convert galactose 1-phosphate into its next product and we can't really convert galactose into galactose 1-phosphate because without this enzyme galactose 1-phosphate is going to build up and there's going to be negative feedback that's going to tell galacto kinase not to convert galactose into galactose 1-phosphate so again just like in the galacto kinase deficiency with a galacto kinase one phosphate your it'll transfer each deficiency there's going to be a preference to shunt the galactose into galactose all so here are our findings and this disease is referred to as classic galactosemia so the pathophysiology here is that we have a deficiency of galacto kinase one phosphate your Riddle transferase and because of this we have an increase in Galacta tall just like we did in our previous disease and an increase in galactose the only difference here is that these are accumulating in much higher volumes and we're gonna get much more severe symptoms so let's talk about the high-yield symptoms and associated findings that you should absolutely know for USMLE and comlex you get really severe cataracts you get liver enlargement so hepatomegaly again this is also autosomal recessive you're very susceptible to sepsis and specifically e-coli sepsis in in infancy this classically will occur when the infant starts feeding right so initially if you start giving them milk and they develop vomiting diarrhea nausea crying after they're fed initially this is where this classically presents so it's going to be when the infant starts feeding you're gonna see an intellectual disability and you're gonna see the color of their skin change so they're gonna get jaundice so how do you remember all this stuff right it's a lot of information I totally get it but dirty medicine has your back just remember classic and galactosemia see for cataracts l4 liver enlargement a4 autosomal recessive s4 sepsis s4 start of feeding so when the infant begins getting milk early in life I for intellectual disability and see for color changes aka jaundice so the first disease was a galacto kinase deficiency and this disease is classic galactosemia so the difference is in the name and the dirty medicine mnemonic is to simply use the name of the disease to help you recall the high-yield findings so really simply guys because the body can't process the galactose the treatment is to just not give them galactose or lactose in their diet now remember that galactose comes from lactose so you don't want to give them the upstream reactant you don't want to give them the lactose you also don't want to give them galactose okay so that's classic galactosemia very very high yield associated findings know about all of these features the last of these three diseases that we're going to talk about in this lecture is actually lactose intolerance now I'm sure many of you have heard about lactose intolerance because it's very common in multiple cultures across the world so really briefly just for completeness sake I'll discuss it here but know that of these three diseases it's the lowest yield lactose intolerance your findings are going to be increased h2 in the breath increase ch4 and increased organic acids you're obviously going to get the symptoms of bloating gas eNOS some diarrhea and you're gonna see a decrease in the pH of the stool so know these findings but don't overly commit this to memory like this is definitely important to know but if you're struggling for brain space know the first two diseases that we talked about there are two types of lactose intolerance one is the primary type so this is basically age determinant so everybody in their life reaches a certain age where the ability of our intestines to process lactose simply is not what it was at Birth the prevailing theory here is that we evolved as humans to need breast milk when we're born and when we reach a certain age we obviously don't need to be breastfed anymore so the intestines would evolve over time to not be able to process milk because evolutionarily speaking you don't need milk after a certain age so that's what's responsible for the primary type of lactose intolerance and this is classically seen in african-americans Asians and even some Native Americans the secondary type of lactose intolerance and the most high-yield part of this slide that you should definitely know is the post viral lactose intolerance so if you get some type of gastroenteritis and you knock out the intestinal brush border because of this inflammation or some type of autoimmune process anything that can damage the intestinal brush border can cause an acquired lactose intolerance because if you damage that intestinal brush border then you cannot process lactose because again the intestinal brush border is the site where lactose gets processed by lactase so no the primary type which depends on your age but no the secondary type especially this is really high yield after a really bad gastroenteritis you could develop the symptoms of lactose intolerance lasts really high you'll point that I need to include about lactose intolerance is that if you do a biopsy or you look at the histology you'll see normal intestinal mucosa and this is so important guys very very high yield buzzword because there's so much different GI pathology that they're gonna go after on USMLE and comlex but lactose intolerance is normal intestinal mucosa so if you see this it helps you rule in or rule out certain things that should be on your differential when you're answering these questions but guys that's it that's galactose metabolism that's the diseases of galactose metabolism know the pathway know the enzymes and know the symptoms especially of the galacto kinase deficiency and classic galactosemia if you know what I've talked about in this video you'll definitely get all of your questions right on test day