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Classic Galactosemia: Ice Cream Example

by Carlo Raj, MD
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    00:01 Well, when you?re consuming ice cream, obviously, you?re gonna stimulate insulin, right? From the pancreatic beta cell.

    00:07 Here comes the insulin and it?s going to facilitate what? Glycolysis or gluconeogenesis? Glycolysis.

    00:14 So quickly here over to the right, we have glucose and then if you?re referring to skeletal muscle and such then we have low Km and a high affinity enzyme called hexokinase or if the glucose is then going to liver or the pancreatic beta cell, enzyme there would be glucokinase which then has a high Km and a low affinity, does it not? Remember that? If you don?t, you might wanna go back and review that real quick because those are important points.

    00:41 You continue further glucose-6-phosphate is what?s been formed.

    00:45 You have a kinase, it?s been phosphorylated.

    00:48 Is that what kinase means in biochemistry? Of course.

    00:51 Now, that you have a glucose-6-phosphate I?ll then move on to what's known as phosphoglucose isomerase.

    00:57 Great, whatever, but most importantly we formed the factor 6 phosphate then you have the rate-limiting enzyme that we all know in love known as phosphofructokinase-1 which then gives us our fructose-1-6-biphosphate.

    01:11 That?s as far as I?m gonna take you there through glycolysis.

    01:13 And what you see here in green represents gluconeogenesis but all important glucose-6-phosphatase.

    01:21 Deficiency of that results in? Give me please.

    01:24 What kind of glycogen storage disease? Type von, in other words type 1 glycogen storage disease, that means it?s von Gierke disease.

    01:34 That?ll help you, right? In the mean time, let?s get back to our focus which is cataracts in a newborn.

    01:43 Accumulation of what exactly causing cataract in classic galactosemia? That was the question.

    01:49 That?s what?s happening here.

    01:51 Glucose-6-phosphate, I want you to follow that now over to the left.

    01:55 What did it turn into? Glucose-1-phosphate.

    01:58 Okay, find the enzyme here it?s called a mutase.

    02:00 Wait, now that you have a glucose-1-phosphate stop there for one second.

    02:04 And if it?s insulin are you gonna promote glycogen synthesis or are you gonna promote glycogenlysis? Glycogen synthesis.

    02:14 Storage of glucose.

    02:15 And then we have an enzyme known as UDP-glucose-pyrophosphorylase which will convert to glucose-6-phosphate into one of the first main substrates for glycogen synthesis called UDP-glucose.

    02:30 That?s as far as we?ll go there in terms of glycogen synthesis.

    02:33 Our track, what was that question? What was the common substrate that you find both in classic galactosemia and glycokinase deficiency resulting cataract formation, formation, formation in this newborn? Well, let?s keep going.

    02:47 Now, come over to the left.

    02:49 And there you have galactose.

    02:51 Hmm, interesting.

    02:52 Where do galactose come from? Galactose.

    02:56 Where do galactose come from? The dairy product, right? Now that galactose, normally, will be converted to galactose-1-phosphate.

    03:06 So if gluco or hexokinase converted glucose into glucose-1-phosphate, guess what galactokinase is going to do? Voila! You formed galactose-1-phosphate.

    03:18 Fantastic! So what if your patient doesn?t have galactokinase? If you know such a thing? Yes.

    03:25 So if this newborn, congenitally, will not have that enzyme called galactosekinase, you?re going to be forcing the galactose going through a pathway known as the aldose reductase pathway.

    03:42 You see that? The aldose reductase found in the lung, liver, kidney, nerves, ovary and seminal vesicle.

    03:54 I?m being very deliberate here.

    03:56 Why? Each one of those organs you could find a pathology in due to the fact that there?s increased accumulation of galactitol.

    04:07 That?s sorbitol.

    04:08 That?s sorbitol.

    04:10 Sorbitol is when glucose, with the help of aldose reductase, turns into sorbitol.

    04:17 That may then give cataracts in diabetic patient.

    04:21 In a patient with galactokinase deficiency, the galactitol may then cause hepatomegaly in this newborn liver.

    04:30 Number two, might have issues in the lung.

    04:34 Number three, might have issues with the kidney, renal disease.

    04:37 Might then have neuropathy, may result in infertility.

    04:43 Now galactose if it?s being forced into the aldose reductase pathway and I?m gonna be deliberate here, but aldose reductase found in the organs of lung, liver, kidney, nerves, ovaries and seminal vesicle.

    04:58 That enzyme should sound extremely familiar to you.

    05:03 The reason for that is in diabetes.

    05:05 If uncontrolled, not properly managed, the glucose with the help of aldose reductase turns into what? Sorbitol.

    05:14 Sorbitol accumulates in the lens may then cause osmotic type of issues in the lens causing cataract.

    05:21 But that?s a diabetic, right? Here we have a newborn with that maybe galactokinase, now for forcing galactose to turn into galactitol.

    05:29 Now each one of these organs may then be affected in the newborn.

    05:33 Go now in alphabetical order.

    05:35 The lung might be respiratory issues.

    05:38 The liver, there might be hepatomegaly.

    05:40 Kidney, might be renal disease.

    05:42 If it accumulates in the nerves will result in neuropathy.

    05:47 Seminal vesicle for the boy, of course, referring to infertility.

    05:52 And unbelievably, even if you were to control the galactokinase deficiency or the other one that I will talk to you about a second called classic galactosemia, there?s no guarantee that your lady, young lady, won?t go into premature ovarian failure.

    06:11 It?s unbelievable.

    06:12 So each one of those organs, extremely important, in that case in which your patient either has galactokinase or let?s move on to our discussion of classic galactosemia.

    06:26 So now let?s say that you did have galactokinase and you formed galactose-1-phosphate.

    06:31 Look over here to the left.

    06:32 You see it? That galactose-1-phosphate is then acted upon by enzyme called?here it is?GALT.

    06:39 G-A-L-T which stands for galactose-1-phosphate uridylyltransferase.

    06:45 That?s the enzyme, please, that you must know where if it?s deficient you?ll result in a newborn that has classic, classic, classic galactosemia.

    06:54 Is that clear? That?s the one that you wanna know.

    06:57 There is another one that I just talked about where galactokinase deficiency.

    07:01 Sure.

    07:02 Now imagine if both of these enzymes were?if one of these enzymes, one or the other, could be deficient in a newborn, what is this newborn going to accumulate? Galactitol.

    07:13 Where? I just gave you the list.

    07:15 Not only could that galactitol then accumulate in these organs, but then may also accumulate early.

    07:20 Go in the lens giving you the congenital cataract that I?ve been referring to.

    07:27 The amount of information that I?ve packed in here in this little diagram is huge.

    07:33 And make sure that you?re well verse with at least what I?ve given you here.

    07:37 At least it?ll give you a little bit of introduction and give you proper application of that homeport subject called biochemistry injected into pathology.

    07:47 Understood? Let?s move on.

    07:50 Congenital, we?ll finish this up.

    07:54 The cataracts that you find in a young newborn by looking at some trisomies again.

    07:59 Remember, in trisomy 13 what?s the letter that you?re thinking? P?Patau, patau, cleft lip.

    08:08 Here we have our cleft palette.

    08:10 And what kind of eyes are you gonna have? Small.

    08:14 Microphthalmus could also have cataracts.

    08:17 What?s a cataract that you?d find in a patient that has rocker bottom feet or the ears are low set and there might be intellectual disability? It?s 18.

    08:29 E as in 18, E as in Edward, right? Trisomy 18.

    08:35 And then of course with 21, we talked about this earlier with Down syndrome and that gave you hypertelorism which means the eyes are spread apart and we also said the iris is then undergoing hypoplasia resulting in what kind of iris? Description or presentation? Brushfield spots.


    About the Lecture

    The lecture Classic Galactosemia: Ice Cream Example by Carlo Raj, MD is from the course Disorders of the Lens. It contains the following chapters:

    • Classic Galactosemia: Ice Cream Example
    • Galactokinase Deficiency
    • Classic Galactosemia

    Included Quiz Questions

    1. Hexokinase
    2. Glucokinase
    3. Galactokinase
    4. Glucose-6-phosphatase
    5. Phosphoglucose isomerase
    1. Glucokinase
    2. Hexokinase
    3. Galactokinase
    4. Glucose-6-phosphatase
    5. Phosphoglucose isomerase
    1. Galactose-1-phosphate
    2. Galactitol
    3. Glucose-1-phosphate
    4. UDP-glucose
    5. UDP-galactose
    1. Galactose-1-phosphate uridyl-transferase
    2. Galactokinase
    3. Phosphoglucose isomerase
    4. UDP-glucose-pyrophosphorylase
    5. Phosphoglucose mutase

    Author of lecture Classic Galactosemia: Ice Cream Example

     Carlo Raj, MD

    Carlo Raj, MD


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