Heme Synthesis Pathway Hey, everyone in this, I’m going to talk to you guys about the heme synthesis pathway. And I’m going to go through each step of the pathway, including going through each of the intermediates of the pathway. And I’m also going to look at particular enzymes in the pathway and how they’re regulated. And I’m also going to tell you, you guys about the importance of heme within our body. So what is heme?
Well, heme is a prosthetic group, so it’s a moiety that is bound to a protein. And heme is actually a protoporphone nine with an iron mountain. What that actually means is that protoporin nine has four Pyro rings. And I’ll get into this bit more the structure of it and how it’s produced a little later. So it has four Pyro rings and it has an iron MUA tea within the center of it.
Heme Synthesis Pathway
And you can see here in this heme molecule, the center iron within the middle of it. So why do we need heme? Well, heme is required for hemoglobin synthesis. And as you already know, hemoglobin is a protein involved in oxygen transport within the red blood cells. And don’t forget the related protein Myoglobin as well, which only has one heme.
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And hemoglobin actually has four heme groups. And myobin is also important in oxygen transport. But nevertheless, when heat is used to produce hemoglobin, we actually call that the Erythropoietic system. And this heme is actually produced in the long bones in our body. And this is actually where about 85% of the heme is produced.
And it’s actually produced for hemoglobin that is actually used in red blood cell and red blood cell production. So another requirement for heme is actually cytochrome synthesis. Now, cytochrome, you may have heard the cytochrome P 450 system within the liver. Now that is the major detoxification pathway in the liver. And cytochromes are critically important in that detoxification system.
Heme synthesis pathway porphyria
Now, they’re very important in hydroxylation reactions to detoxify particular drugs and compounds. And when heme is actually produced for cytochrome synthesis, we call that the hepatic system. And again, as I mentioned before, this hepatic production of heme is critically important for cytochrome P 450 system within the liver.
So how does heme production start? Well, it actually starts with the amino acid glycine and succinct away. And these two components are actually used by an enzyme known as Alase synthase or aminolveinic acid synthase. In this process, it actually occurs within the mitochondria to produce amino levy Linux acid. Now, this step in the heme synthesis pathway is the first step, but is actually the right limiting step of the heme synthesis pathway.
Now, within the hepatic system, Hemen, which is a byproduct of heme, actually negatively inhibits Alasynthase. While reduced hepatic, heme actually upregulates Ala synthase. So you can actually have reduced hepatic Heem if you over utilize that cytochrome P 450 system by, say, for instance, ingesting too much of some drug or some toxic compound, the Cyclone T 457 become over utilized and would actually require more heme production. And that is why a reduced appetite, Hein would actually upregulate this enzyme to compensate. Now, in the erythropoietic system, iron and erythropoietin are actually the activators or up regulators of this enzyme.
Heme synthesis pathway mnemonic
So once we have produced amino levy Linux acid, it actually takes two of them to actually go onto the next step. And the next step involves Aladhydrates, which actually occurs in the cytosol. And this produces something known as porphobalinogen. And this enzyme actually requires zinc. And because it requires a metal, it can actually be inhibited by lead.
So we all have heard that lead can cause anemia. And this is why lead actually can inhibit this enzyme or inhibit Ala dehydrates. So once we have porphobalinogen, it actually takes four porfobalinogens to move on to the next step. And once you have four of these, the enzyme europorinogen one synthase will actually take these four porphylanogens. And in the cytosol, this is all happening in the cytosol will release four ammonia and will actually produce europorphoneogen one.
Now, europorinogen one will actually be processed by europoorring three cosine days. Also in the cytosol into europortogen three. Europoorfriendogen three will then undergo a reaction with europulinogen decarboxyles to produce copper porphyrine three. So I know, guys, this is a lot of big words, but we’ll get through it. So copper porphyringen three is produced from europofrigian three by the enzyme europorthigen decarboxylase.
Heme synthesis SlideShare
Now copper porn free will actually undergo another step by the enzyme copper porphyrine oxidase into protoporinogen nine. So we’re getting close there. You can see as we’re moving on, this structure is becoming more and more like heme. So protoporagin nine is produced and then we’ll actually go through portoportengine oxidize to produce protoporin nine. So we’re pretty much there.
But we’re missing one thing, and that is the iron. And the iron will actually come from the last step by the enzyme Pharaoh Achilles. And this actually happens in the mitochondria as well. So this is where iron is actually added to this protoporin nine molecule. And this is when you actually have full, fully fledged heme.
And again, because we’re using a metal, we’re using a metal ion in this reaction. This reaction can actually be inhibited by lead again. So lead can inhibit this reaction as well as the Alabras reaction. So just remember that guys, lead can inhibit both the second step of the pathway as well as the last step of the pathway. It can inhibit both Ala dehydrates and inhibit ferrokeyletase leading to anemia.
Regulation of heme synthesis
And that’s why leads to anemia. So I know this is a lot of big words. You might find that it’s not easy to remember all of this, but all I would suggest is that you guys remember a few of the enzymes. And I would suggest you remember the first enzyme because that’s the rate limiting enzyme, the Ala synthase. I’d also suggest remembering Aladdhydrates because that’s where lead actually acts and that’s the second step of the pathway and I’d also say you should remember ferroquilitaze the last enzyme of the pathway because this is also where lead is an inhibitor.
So those are the three big key enzymes that I want you guys to remember and an easy way to remember the name or the steps of the pathway. I kind of always think of something called APOC PP and now it’s a funny way of remembering it but the a can stand for amino lebulinic acid, the P can stand for porphobalinogen, the U can stand for a europorinogen one, the other U europorinogen three, the C for copper porphyrinogen three, the P protoporinogen nine and then the other P protoporefriend. And the last one of course, is heme so that might help you guys out. I would just suggest going through this a couple of times to get it full better Fuller understanding of this pathway. Anyways, guys I hope that helped.
FAQs
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Conclusions
As scientists continue to explore the heme synthesis pathway, they are discovering new and exciting ways in which this process can be used to develop new drugs and therapies. By understanding the heme synthesis pathway at a molecular level, it is possible to design better inhibitors and promoters of this important process, paving the way for more effective treatments for diseases such as cancer.
