Vitamin B12 (Cobalamin)

00:00 So now let's move on to B12 or cobalamin.

00:06 As you can imagine B12 has some similar manifestations or deficiency of as we see in B6.

00:14 But B12 is the one that is stored in liver.

00:19 Primarily we also see B9 as a I mentioned before.

00:22 But B12 has a years worth of storage actually in the liver.

00:29 So B12 deficiency is only something we really have to consider when people are not consuming animal proteins because B12 is found in animal products.

00:42 Specifically liver is a great source of B12.

00:46 Because as we store it there, other animals store it there too.

00:52 So B12 is involved in a number of things including nerve cell function and red blood cell production.

01:00 I bet that's no mystery to you.

01:02 And fatty acid oxidation.

01:05 So B12 deficiencies actually have manifestations beyond that of B9 deficiencies.

01:14 So wanted to remind you about fatty acid oxidation.

01:18 Here you can see an image from our molecular and cell biology lectures talking about fatty acid oxidation.

01:26 You can see these multicarbon units being chopped up into two carbon sub units attached to acetyl CoA.

01:33 And then those can enter Krebs cycle and be metabolized.

01:37 Now we'll address an issue with the metabolism of fatty acids.

01:43 We know that they get chopped off in pairs.

01:46 But what happens when we don't have pairs.

01:48 What if it's an odd number chain.

01:50 So that is where is we'll see B12 coming into, cause some issues or shortage in it.

01:58 Coming into cause some issues.

02:00 Before we go there to the pathway piece, let's look at cobalamin absorption.

02:07 Because it needs to have digestive enzymes to break down the proteins necessary to remove the B12, right.

02:16 That makes sense.

02:17 So in the case of B12, we definitely need stomach acid as we do with other vitamins but in addition, we need to have intrinsic factor.

02:29 An intrinsic factor is picked up in the stomach from the parietal cells.

02:35 So the parietal cells secrete intrinsic factor.

02:38 The B12 is bound to an intrinsic factor.

02:41 And then those guys make their way through the digestive system until they get to the terminal ilium.

02:49 So intrinsic factor is essentially chaperoning B12 through the digestive system to the terminal ilium where it then can be absorbed.

03:00 So now you know what you need to know about the absorption of vitamin B12.

03:07 Let's take a look at some of the things that could lead to a deficiency in B12.

03:14 First of all pernicious anemia.

03:17 Pernicious anemia is an autoimmune disease and it actually effects the parietal cells.

03:23 And if they can't secrete intrinsic factor as is the case with pernicious anemia, then there is no intrinsic factor in the stomach.

03:32 And there is nothing for the B12 to bind to.

03:35 And thus, it does not travel so safely through the digestive track.

03:41 Gets broken down and we see B12 deficiency.

03:45 Another thing that can cause a deficiency in B12 is the use of antacids or overuse of antacids and proton pump inhibitors.

03:56 Because they prevent the breakdown of proteins.

04:00 And because we're decreasing the acidity in the stomach.

04:06 And thus, decrease the release of B12 and it's picking up by intrinsic factor and so on and so forth.

04:12 Another drug that can have a big impact on B12 is metformin.

04:18 Metformin is a drug used in the treatment of diabetes type II.

04:23 And it is known to decrease B12, decrease the amount of B12.

04:31 So, whenever you have patients that are on any of these therapies, we need to consider supplementation with B12.

04:39 The other things that can of course impact B12 deficiency, is someone who has had part of their bowel removed.

04:49 Or who has an absorption disorder like crohn's disease.

04:53 And glutenin intolerances such as celiac disease.

04:59 So all sorts of things can lead to a deficiency in cobalamin.

05:07 So let's look at that pathway again for folate.

05:14 Again recall that the objective here was to take dietary intake of folate and turn it into the production of DNA.

05:24 So that cells can get pass that G1 as checkpoint and replicate the DNA.

05:31 So if we don't have any B12, then we cannot recycle methyltetrahydrofolate and make it into tetrahydrofolate.

05:45 Recall that methyltetrahydrofolate unless it's recycled.

05:48 Can't go on to do anything useful as far as DNA nucleotide production.

05:55 So we have here the same symptoms showing up as we would see for B9 deficiency.

06:01 But wait, there's more.

06:05 Here we go with the nervous system issues that are associated with B12 deficiency.

06:13 So not only do we see B9 symptoms.

06:17 We see lots of neurological symptoms and this is why.

06:21 Another pathway I know but I'm sure you can handle this one it is I swear simpler than it looks.

06:28 First of all let's understand that in fatty acids metabolism, we have these two sub unit pieces again getting attached to CoA and they should go through this pathway and enter into the Krebs cycle just fine, right.

06:46 Acetyl CoA.

06:48 But, when we're left with these three carbon segments we have a little bit of a problem, right.

06:54 Somebody is going to get left out.

06:56 So the three carbon fragments are going to be converted into methylmalonyl coenzyme A, right.

07:05 And that methylmalonyl coenzyme A would then get converted in the presence of all the right cofactors into succinyl CoA.

07:14 And succinyl CoA can enter the Krebs cycle at a different point than acetyl CoA would have, right.

07:22 So, here we have three carbon fragments that are then converted into a two carbon fragment and a one carbon fragment.

07:32 And that one carbon fragment can go into the Krebs cycle without any problems.

07:39 But, if we don't have any B12 present, we have no cofactor to help the conversion of methylmalonyl coenzyme A into succinyl CoA and we shut the program down.

07:54 And when we shut that program down, we end up with a build up of methylmalonic acid.

08:00 Okay, so what? We've got methylmalonic acid.

08:05 What's the big deal with extra methylmalonic acid? Well if it accumulates in significant quantities we start to see some neurological issues.

08:14 Because methylmalonic acid actually stops or prevents or interferes with myelination of neurons.

08:21 So we will see symptoms like peripheral numbness and tingling as well as some muscle spasticity.

08:28 Because neurons aren't sending signals properly because the methylmalonic acid is causing demyelination.

08:36 And we'll see also loss of proprioception.

08:40 So people may not be quite aware of where their limbs are in space.

08:45 Began because of neuro signaling.

08:47 So again lots of different symptoms for B12 and it's tightly tied to B9 deficiencies.

08:57 And these two are things that you should certainly know the pathways for.

09:03 Understand how methylmalonic acid accumulates.

09:06 As well as how folate metabolism works.

09:09 And the role of B12 in that.

09:12 So big material, super highlights that you need to keep in mind.