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Vitamin K

by Kevin Ahern, PhD
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    00:01 In this lecture, we’ll focus on two of the fat-soluble vitamins, vitamins K and E.

    00:06 And twp groups of molecules involved that what we call one-carbon metabolism, vitamin B12 and another group of molecules called the folates.

    00:16 Now, vitamin K is a fat-soluble vitamin that plays very important roles in the blood clotting process and also an important role in maintaining bone health.

    00:26 Like the other fat-soluble vitamins, vitamin K is stored in fat tissue.

    00:30 It is found very abundantly in green leafy vegetables like kale, spinach and collards.

    00:36 It’s a compound that’s stable in the air, but it does decompose when exposed to sunlight.

    00:41 There are several forms of vitamin K including natural forms that are found in nature and man-made forms that also appear to function in a similar fashion.

    00:51 Vitamin K-related modifications facilitate the binding of calcium to target proteins.

    00:58 And this is what really vitamin K’s function is in both the blood clotting process as well as in maintaining bone health.

    01:05 It’s the absence of vitamin K that leads to uncontrolled bleeding in an individual.

    01:10 Meaning of course that vitamin K is essential for the clotting process.

    01:14 A deficiency of vitamin K, however, is relatively rare in healthy adults.

    01:19 And it is required for bone formation.

    01:22 Vitamin K is actually a group of molecules.

    01:26 Now, the form known as vitamin K1 is also known as phylloquinone.

    01:29 It’s an electron acceptor that is found in plants in the photosynthesis system known as photosystem I.

    01:36 As I said, it’s found in the green leaves and because of the chlorophyll that the plants have, this compound is quite abundant in those plants.

    01:43 Vitamin K is involved in carboxylation.

    01:46 It is adding carboxyl group to the glutamates side chains of the blood clotting factors.

    01:51 This includes blood clotting factors II, VII, IX and X.

    01:56 Vitamin K can also be involved in the carboxylation of other compounds, in the preventing a clotting process as well as some proteins.

    02:03 So some of the anticoagulation factors that a vitamin K can carboxylate includes the glutamate side chains of factors protein C and S.

    02:13 So we can imagine that vitamin K’s role of carboxylation is very important one.

    02:17 And we will see in a minute why that is the case.

    02:21 So as I said, vitamin K is a group of molecules.

    02:23 Vitamin K2 is known as menaquinone and is a group of compounds that differ in a number of isoprene units that they have.

    02:30 An isoprene unit is a group of carbons and hydrogens that are shown in the figure on the right in the bracketed portion.

    02:37 They actually contain five carbons and the rest being hydrogens.

    02:40 The isoprene unit is the way that the molecule is built.

    02:44 So molecules that are built using this vary in how many they have and therefore vary in their sizes according to five carbon units.

    02:51 MK-4 also known as menatetrenone and MK-7 are subtypes of vitamin K2.

    02:58 They are also involved in glutamate carboxylations as is K1 and they're involved at the same level as vitamin K1 is.

    03:06 Vitamin K1, as I said, is found in plants.

    03:09 But bacteria take that vitamin K1 that we get in our diet and they convert vitamin K1 to vitamin K2 and another form known as MK-7 as well as MK-8, MK-9, MK-10 and MK-11.

    03:22 So you see that there are quite a variety of these K’s that are present in our body.

    03:28 MK-4 also known as menatetrenone can be produced by animals in their testes, pancreas and arteries.

    03:35 And it turns that it’s the only form of K2 that is actually made by animals.

    03:39 So we see that bacteria play a very important role in us being able to have the right vitamin K that we need in our body and they do this through metabolism residing in our gut.

    03:51 So these are three synthetic forms of vitamin K that you can see on the screen that are man-made, but they all will also function in the capacity of vitamin K.

    03:59 This includes vitamin K3 (menadione), vitamin K4 is shown here and vitamin K5.

    04:06 And all of these appear to be pretty fairly safe with the exception of vitamin K3 which in higher doses can be toxic.

    04:15 Vitamin K, as I said, is needed for carboxylation of proteins.

    04:18 So let’s take a minute to understand how that happens.

    04:21 Here is the amino acid glutamate which is found within a polypeptide chain.

    04:27 We can see its side chain that contains the carboxyl group at the very top of this molecule.

    04:32 Catalysis by the enzyme glutamate carboxylase using oxygen, carbon dioxide, water and protons produces a modified form of glutamate known as gamma carboxyglutamate.

    04:45 This gamma carboxyglutamate has an extra carboxyl group that is added to it.

    04:50 And that turns out to be critical for the function of this protein because with this added carboxyl group, the molecule can bind calcium.

    04:58 Now, calcium, as we’ve seen over and over in these lectures, is very important for a variety of processes.

    05:04 And in the blood clotting process, calcium is abundant at the place of the clot.

    05:09 So the ability of blood clotting proteins to bind to calcium helps them to remain at the site of the wound to help the clotting process to occur.

    05:20 The way that vitamin K fits into the scheme is vitamin K is a co-factor for the glutamate carboxylase.

    05:28 This co-factor allows glutamate carboxylase to do what it does.

    05:33 In the reaction that’s catalyzed by putting the hydroxyl group on, this is a very unusual reaction again using molecular oxygen.

    05:40 Vitamin K acts as an acceptor of one of the atoms of oxygen.

    05:46 So you can see that vitamin K in this reaction is converted to an unusual molecule called vitamin K epoxide.

    05:53 And that oxygen, that vitamin K accepted from the oxygen, is pressed in a three-membered triangular ring on the right side of the molecule.

    06:02 In order for the vitamin K to function in the body, it has to be reconverted back to its original form by an enzyme.

    06:10 If that reconversion back doesn’t occur, then the body will eventually run out of vitamin K and the person will lose the ability to clot blood.

    06:19 So the recycling process, vitamin K epoxide that oxygen-containing molecule is very critical.

    06:26 Recycling is essential for the body to have the clotting factors that it needs.

    06:30 Well, the reaction that needs to happen is actually a fairly simple one, although it’s kind of odd.

    06:35 It involves the loss of water from vitamin K epoxide as the reaction shows and that involves the removal of two hydrogens from the two carbons attached to the oxygen.

    06:44 And those two carbons bind to the oxygen itself producing water.

    06:48 That results in the reproduction of vitamin K.

    06:52 This reaction is catalyzed by a very important enzyme known as vitamin K epoxide reductase.

    06:58 Now, vitamin K epoxide reductase is present in normal amounts in the cells and this reaction occurs pretty routinely and you don’t think about it.

    07:06 But there are people, for example, who have problems with clotting.

    07:10 Those people who have problems with clotting may lose a limb.

    07:13 They may have problems with heart attacks or stroke.

    07:15 And it’s known it is fairly easy to measure a person’s clotting ability, how clotting tendencies that a given person’s blood has.

    07:24 If you’re a person who has blood that tends to clot more readily or form clots more readily, your doctor may put you on what’s known as a blood thinner.

    07:32 And blood thinner is a molecule that inhibits this reaction.

    07:37 One of the blood thinners that is commonly used is known as warfarin or also called Coumadin.

    07:42 Warfarin is also known rat poison.

    07:46 So some of the people that you know who take blood thinning medications are actually taking a form of rat poison.

    07:52 Well, they're not getting poisoned of course because a person who was given this as a treatment by their doctor is given it in limited dose.

    08:00 So it takes a certain amount of warfarin to reduce the clotting to a level that is acceptable.

    08:06 Too much warfarin, you can imagine, will result in too little clotting.

    08:10 When you have too little clotting, you can die of hemorrhage.

    08:13 So getting the right level of clotting is important and warfarin can play a very important role in establishing the right level within a person.

    08:22 Once the person is on warfarin, they will periodically have to go to their doctor to get tested regularly to see if their clotting tendency has changed.

    08:29 And then the amount of warfarin that they’re given will be adjusted accordingly.

    08:34 Warfarin blocks vitamin K cycling, as I said.

    08:38 The lack of vitamin K stops protein carboxylation.

    08:41 And that protein carboxylation is critical for the clotting process.

    08:45 And low protein carboxylation can slow the blood clotting.

    08:51 Vitamin K is also important for bone health.

    08:54 It stimulates the carboxylation of bone proteins and activates many of them.

    08:58 And this turns out to be important because we remember that bones are abundant source of calcium.

    09:05 Three of the proteins that vitamin K carboxylates are shown below.

    09:08 The first is osteocalcin.

    09:10 It binds to the bone matrix and stimulates osteoblasts.

    09:14 And it does this of course by binding that calcium.

    09:17 If it gets carboxylated by vitamin K appropriately, then that binding will occur and the bone matrix will be stimulated.

    09:26 The matrix gla or gla protein also binds calcium and it organizes bone tissue in the proper fashion.

    09:34 And the last is periostin and it’s involved in the cell migration during bone development and maybe overexpressed in some cancers.


    About the Lecture

    The lecture Vitamin K by Kevin Ahern, PhD is from the course Vitamins. It contains the following chapters:

    • Vitamins K, E, B12, and Folate Metabolism
    • Vitamin K Metabolism
    • Vitamin K Recycling

    Author of lecture Vitamin K

     Kevin Ahern, PhD

    Kevin Ahern, PhD


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