0:02 welcome back to dirty medicines dirty
0:05 biochemistry series this video is on the
0:09 disorders of galactose metabolism if I
0:11 can pause for a second and just lay out
0:12 kind of how we're going to go through
0:15 this video we're going to start by
0:17 outlining the normal biochemistry so I'm
0:19 going to give you the pathway about how
0:21 we start with lactose and convert it
0:23 into different sugars and work our way
0:25 through the pathway of galactose
0:28 metabolism along the way I'll show you
0:31 what three diseases will manifest if we
0:33 knock out certain enzymes that is to say
0:35 if we have certain enzymatic
0:37 deficiencies as I go through these
0:40 diseases I'll give you my awesome dirty
0:42 medicine mnemonics to help you remember
0:44 the hi old findings that you'll be asked
0:47 to know on test day when you sit for us
0:48 Emily or comlex
0:51 so let's begin by talking about lactose
0:54 which is our starting material lactose
0:57 can be converted into both glucose and
0:59 galactose the enzyme that converts
1:02 lactose into galactose is lactase
1:04 another way of saying this is that the
1:08 enzyme lactase breaks down lactose now
1:09 think about the name you've probably
1:11 heard about lactose intolerance before
1:13 and you're also probably aware that this
1:15 is due to a problem with the lactase
1:17 enzyme but if you look at the name
1:20 lactase it's telling you that it's acing
1:23 or breaking down lack'd or lactose so
1:24 that's where the name comes from
1:27 so again lactose is converted into
1:30 galactose by lactase now everything you
1:32 see here shown in the gray box is
1:35 occurring at the brush border of the
1:37 small intestine we'll come back at the
1:39 end of this video and talk about lactose
1:41 intolerance because of the three
1:43 diseases of galactose metabolism it's
1:47 the lowest yield next galactose can be
1:50 converted also into one of two different
1:53 products one is galactose 1-phosphate
1:56 and the other is Galacta tall now you
1:58 need to know both of the enzymes that
2:00 convert galactose into these two
2:02 different products the enzyme that
2:05 converts galactose into Galacta tall is
2:08 aldose reductase the enzyme that
2:10 converts galactose into galactose
2:13 1-phosphate is galacto kinase now
2:15 just as an aside sort of a big picture
2:17 high-yield way of remembering some
2:20 biochemistry whenever you see an enzyme
2:22 that ends in kinase it means it's just
2:24 putting a phosphate group on whatever
2:27 the reactant is so in this case you
2:29 start with galactose and it gets a
2:32 phosphate in the one position and that's
2:35 why the enzyme is galacto kinase because
2:37 it's kinase Anor sticking a phosphate on
2:40 galactose this also helps explain why
2:42 the product is galactose 1-phosphate
2:45 because it has one phosphate stuck onto
2:48 it by galacto kinase so keep that in
2:49 mind if you're ever struggling with
2:52 enzyme names reactants and products
2:56 now galactose 1-phosphate can be
2:58 converted into glucose 1-phosphate by
3:01 the enzyme galacto kinase one phosphate
3:04 your it'll trance race in this step you
3:07 need UDP glucose to be converted into
3:11 UDP galactose as a cofactor now this
3:13 step is extremely extremely important to
3:15 understand and it's very high yield
3:17 we'll talk about it in a little bit
3:20 about knocking out this enzyme and what
3:23 disease you get if that happens now once
3:25 you have glucose 1-phosphate you should
3:27 be a little bit familiar with this
3:29 product glucose 1-phosphate
3:31 has a lot of downstream options it can
3:33 enter glycolysis it could enter glycol
3:36 Genesis it can be used in a ver in a
3:39 variety of biochemical pathways so
3:40 keeping with our theme that we've seen
3:42 throughout the dirty biochemistry series
3:45 different reactions are generating
3:47 different products which can be used by
3:50 other biochemical pathways so this is
3:52 the main pathway of galactose metabolism
3:54 and you need to know the enzymes shown
3:56 in red you also need to know the
3:59 cofactor shown in green now let's talk
4:01 about what happens if you have certain
4:04 enzyme deficiencies the first disease
4:06 that we'll talk about is what you get if
4:09 you knock out galacto kinase so shown in
4:11 this large blue X we have an enzyme
4:15 deficiency of galacto kinase now think
4:17 about this by looking at our pathway if
4:20 you don't have galacto kinase then you
4:22 cannot convert galactose into galactose
4:25 1-phosphate so you can't do the blue
4:27 dotted line instead
4:29 this will be shunted to the blue thick
4:31 line so galactose will be converted into
4:35 Galacta tall by aldose reductase so by
4:38 simply knocking out galacto kinase we
4:40 have a preference to divert galactose
4:44 into galactose all this disease is aptly
4:47 named a galacto kinase deficiency so
4:49 again what do you have here you have a
4:52 decrease of the enzyme galacto kinase
4:54 you have a decrease of the product
4:57 galacto kinase one phosphate because you
4:59 cannot convert the reactant into the
5:02 product instead you have an increase of
5:04 Galacta tall because the pathway gets
5:07 shunted in preference of converting
5:10 galacto kinase into Galacta tall so
5:12 these are the findings that you need to
5:14 be familiar with for a galacto kinase
5:16 deficiency but there are a lot of
5:18 clinical findings and other high-yield
5:19 features that you could be required to
5:23 know on USMLE or complex and that's what
5:25 we're going to talk about now the other
5:26 things that you should know about a
5:28 galacto kinase deficiency are that
5:31 you'll see galactosemia which means
5:33 galactose in the blood right
5:35 amia means blood so galactose emia
5:39 galactose in the blood galactose urea
5:42 which urea means urine so galactose in
5:45 the urine so galactose in the blood and
5:46 the urine because we have a lot of
5:48 galactose that's accumulating since we
5:51 cannot use galacto kinase you'll have
5:53 abnormal eye tracking i'll come back to
5:55 this in just a second but you're gonna
5:57 see a lot of visual difficulties when
5:59 you have an accumulation of galactose
6:02 all lack of the development of a social
6:04 smile this is an autosomal recessive
6:07 disease and you'll see infantile
6:10 cataracts now overall galacto kinase
6:12 deficiency is really not a severe disease
6:12 disease
6:14 so you see infantile cataracts that
6:17 aren't that bad and you see abnormal eye
6:19 tracking when you have an accumulation
6:22 of a substance like Galacta tall that
6:24 substance actually gets trapped in the
6:27 lens of the eye and when that happens
6:28 you get the cataracts and you get
6:31 abnormal eye tracking so how do you
6:33 remember all of these high heel findings
6:35 well you should remember this by
6:37 remembering galacto kinase deficiency
6:41 gee al AC G
6:43 for galactosemia and Galactus urea
6:46 because that galactic galactose is
6:48 accumulating in the blood and
6:50 accumulating in the urine a for abnormal
6:53 eye tracking because there's an increase
6:54 in Galacta tall which is being trapped
6:57 in the eye L for lack of a social smile
7:00 during development a for autosomal
7:04 recessive disease and C for infantile
7:06 cataracts or just cataracts so that's
7:09 galacto kinase deficiency and it's
7:11 really not as bad as the next disease
7:13 that we're going to talk about so again
7:16 this is a galacto kinase deficiency when
7:19 you knockout galacto kinase now let's
7:22 talk about the more severe form of a
7:24 galacto kinase problem and that's if we
7:26 actually knock out the next enzyme in
7:28 the pathway we knock out galacto kinase
7:31 one phosphate your it'll transfer ace so
7:33 this is a really severe disease much
7:35 more severe than the galacto kinase
7:37 deficiency and the reason is that
7:39 because this enzyme is processing a lot
7:41 more of the galactose load in the body
7:43 so if you knock this one out the
7:45 symptoms are going to be way more severe
7:47 and you're gonna get a greater
7:49 accumulation of products in the body and
7:52 it's that accumulation of products that
7:55 isn't normally there that causes all of
7:57 the symptoms so look at our pathway if
7:59 we knock out galacto kinase one
8:02 phosphate your Riddle trance race then
8:05 we can't do the two blue dotted lines we
8:06 cannot convert galactose 1-phosphate
8:09 into its next product and we can't
8:11 really convert galactose into galactose
8:13 1-phosphate because without this enzyme
8:15 galactose 1-phosphate is going to build
8:16 up and there's going to be negative
8:18 feedback that's going to tell galacto
8:20 kinase not to convert galactose into
8:24 galactose 1-phosphate so again just like
8:26 in the galacto kinase deficiency with a
8:28 galacto kinase one phosphate your it'll
8:30 transfer each deficiency there's going
8:32 to be a preference to shunt the
8:35 galactose into galactose all so here are
8:37 our findings and this disease is
8:40 referred to as classic galactosemia so
8:42 the pathophysiology here is that we have
8:44 a deficiency of galacto kinase one
8:46 phosphate your Riddle transferase and
8:48 because of this we have an increase in
8:50 Galacta tall just like we did in our
8:52 previous disease and an increase in
8:55 galactose the only difference here is
8:56 that these are accumulating in much
8:59 higher volumes and we're gonna get much
9:01 more severe symptoms so let's talk about
9:03 the high-yield symptoms and associated
9:05 findings that you should absolutely know
9:07 for USMLE and comlex
9:11 you get really severe cataracts you get
9:14 liver enlargement so hepatomegaly again
9:17 this is also autosomal recessive you're
9:19 very susceptible to sepsis and
9:23 specifically e-coli sepsis in in infancy
9:25 this classically will occur when the
9:28 infant starts feeding right so initially
9:29 if you start giving them milk and they
9:33 develop vomiting diarrhea nausea crying
9:35 after they're fed initially this is
9:37 where this classically presents so it's
9:38 going to be when the infant starts
9:41 feeding you're gonna see an intellectual
9:42 disability and you're gonna see the
9:44 color of their skin change so they're
9:46 gonna get jaundice so how do you
9:47 remember all this stuff right it's a lot
9:49 of information I totally get it
9:53 but dirty medicine has your back just
9:56 remember classic and galactosemia see
9:59 for cataracts l4 liver enlargement a4
10:02 autosomal recessive s4 sepsis s4 start
10:04 of feeding so when the infant begins
10:06 getting milk early in life I for
10:09 intellectual disability and see for
10:10 color changes
10:14 aka jaundice so the first disease was a
10:16 galacto kinase deficiency and this
10:20 disease is classic galactosemia so the
10:22 difference is in the name and the dirty
10:24 medicine mnemonic is to simply use the
10:26 name of the disease to help you recall
10:29 the high-yield findings so really simply
10:32 guys because the body can't process the
10:34 galactose the treatment is to just not
10:37 give them galactose or lactose in their
10:39 diet now remember that galactose comes
10:41 from lactose so you don't want to give
10:42 them the upstream reactant you don't
10:44 want to give them the lactose you also
10:46 don't want to give them galactose okay
10:49 so that's classic galactosemia very very
10:51 high yield associated findings know
10:54 about all of these features the last of
10:55 these three diseases that we're going to
10:57 talk about in this lecture is actually
11:00 lactose intolerance now I'm sure many of
11:02 you have heard about lactose intolerance
11:05 because it's very common in multiple
11:07 cultures across the world so really
11:08 briefly just
11:10 for completeness sake I'll discuss it
11:12 here but know that of these three
11:15 diseases it's the lowest yield lactose
11:16 intolerance your findings are going to
11:19 be increased h2 in the breath increase
11:22 ch4 and increased organic acids you're
11:23 obviously going to get the symptoms of
11:26 bloating gas eNOS some diarrhea and
11:28 you're gonna see a decrease in the pH of
11:31 the stool so know these findings but
11:34 don't overly commit this to memory like
11:36 this is definitely important to know but
11:37 if you're struggling for brain space
11:39 know the first two diseases that we
11:41 talked about there are two types of
11:43 lactose intolerance one is the primary
11:45 type so this is basically age
11:47 determinant so everybody in their life
11:49 reaches a certain age where the ability
11:51 of our intestines to process lactose
11:54 simply is not what it was at Birth the
11:56 prevailing theory here is that we
11:59 evolved as humans to need breast milk
12:02 when we're born and when we reach a
12:03 certain age we obviously don't need to
12:05 be breastfed anymore so the intestines
12:08 would evolve over time to not be able to
12:11 process milk because evolutionarily
12:13 speaking you don't need milk after a
12:15 certain age so that's what's responsible
12:17 for the primary type of lactose
12:18 intolerance and this is classically seen
12:21 in african-americans Asians and even
12:24 some Native Americans the secondary type
12:26 of lactose intolerance and the most
12:27 high-yield part of this slide that you
12:30 should definitely know is the post viral
12:33 lactose intolerance so if you get some
12:36 type of gastroenteritis and you knock
12:38 out the intestinal brush border because
12:40 of this inflammation or some type of
12:43 autoimmune process anything that can
12:45 damage the intestinal brush border can
12:47 cause an acquired lactose intolerance
12:50 because if you damage that intestinal
12:51 brush border then you cannot process
12:54 lactose because again the intestinal
12:56 brush border is the site where lactose
12:59 gets processed by lactase so no the
13:01 primary type which depends on your age
13:03 but no the secondary type especially
13:05 this is really high yield after a really
13:07 bad gastroenteritis you could develop
13:09 the symptoms of lactose intolerance
13:12 lasts really high you'll point that I
13:13 need to include about lactose
13:15 intolerance is that if you do a biopsy
13:18 or you look at the histology you'll see
13:21 normal intestinal mucosa and this is so
13:22 important guys
13:24 very very high yield buzzword because
13:26 there's so much different GI pathology
13:28 that they're gonna go after on USMLE and
13:32 comlex but lactose intolerance is normal
13:35 intestinal mucosa so if you see this it
13:36 helps you rule in or rule out certain
13:38 things that should be on your
13:40 differential when you're answering these
13:42 questions but guys that's it
13:44 that's galactose metabolism that's the
13:47 diseases of galactose metabolism know
13:49 the pathway know the enzymes and know
13:52 the symptoms especially of the galacto
13:54 kinase deficiency and classic
13:56 galactosemia if you know what I've
13:57 talked about in this video you'll
13:59 definitely get all of your questions
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