Pathway Overview and Reactions – Part 1

00:00 Now the pathway I’ve drawn here is a little unusual.

00:04 This isn’t the way the pathway is commonly drawn.

00:06 But in fact, it shows all the reactions of the pathway and some of the crosses that happen.

00:10 This is sometimes a pathway that’s difficult for students to learn because in the multiple directions that it can take.

00:16 We’re going to go through the individual reactions in just a bit.

00:19 But I want to show you first of all, the connections of the Pentose Phosphate pathway to the other pathways that are important in the cell.

00:26 I said for example, there are several intermediates important in glycolysis and gluconeogenesis.

00:31 Gluconeogenesis of course being the reverse of glycolysis.

00:33 We see glucose 6-phosphate, we see glyceraldehyde 3-phosphate and we see fructose 6-phosphate as well coming from glycolysis.

00:43 We see an intermediate and nucleotide synthesis as I’ve noted ribose 5-phosphate shown here.

00:48 And we also have erythrose 4-phosphate which is important for amino aromatic amino acid synthesis.

00:54 Now, this provide both entrance points and exit points into the pathway.

01:00 Now, the first reaction of the Pentose Phosphate pathway is labelled here.

01:05 This reaction is catalyzed by the enzyme glucose-6-phosphate dehydrogenase.

01:10 In this process, glucose-6-phosphate is converted into 6-phosphoglucono-delta-lactone Now, full the name, which I abbreviated to 6-PG delta L.

01:23 This is the first of two oxidations that happens in the Pentose Phosphate pathway.

01:28 and is one of the sources of NADPH produced by the pathway.

01:32 So, this reaction that you see, I often describe this as rate limiting step in the process of the Pentose Phosphate pathway.

01:38 And it’s true that it is rate limiting for the entry of glucose 6-phosphate.

01:42 But since we have multiple points of entry into the pathway, it’s not as important as it might otherwise seem.

01:47 The reaction is inhibited by the molecules acetyl-CoA and NADPH.

01:52 Acetyl-CoA and NADPH of course are indicators the fact the cell has plenty of things, plenty of intermediates and doesn’t need to be making other things like NADPH.

02:02 And so, the enzyme gets turned off when they bind to it.

02:05 Deficiency of the enzyme that catalyzes this reaction can lead to acute hemolytic anemia due to reactive oxygen species damages that happens from lack of reduced glutathione where the NADPH is needed to make glutathione.

02:20 So, if we ran out of it of NADPH then we will have not enough glutathione to help protect cell from reactive oxygen species.

02:28 A deficiency of this enzyme on the other hand, may give some protection to people who get infected by malarial parasites because malarial parasites require more NADPH for them to function.

02:40 The second process of the second reaction cell is depicted in the rectangle here. We’ll look at a little bit closely up here.

02:46 We see in this reaction that 6-phosphoglucono-deltalactone is hydrolyzed using water to open the ring structure that we see in the top molecule to a linear at the bottom.

02:56 Now, this turns out to be important because in the next reaction that end of the molecules kind of get broken off and it wouldn’t get broken off if it wasn’t the ring structure.

03:04 This enzyme that catalyzes the reaction is 6-phosphoglucono-lactase as you can see here.

03:09 And this linearization as I noted is important to allow the molecule in the next reaction to be decarboxylated.

03:15 In the next reaction 6-phosphogluconate is oxidized and the only decarboxylation reaction of the Pentose Phosphate pathway.

03:23 We see 6-phophogluconate at the top molecule here being oxidized and the decarboxylation occurring to make the five carbon molecule ribulose diphosphate in the reaction below.

03:34 6-phosphogluconate of course has six carbons.

03:37 This reaction produces NADPH and this second and the last reactions of the Pentose Phosphate pathway that make NADPH.

03:45 The enzyme catalyzing this reaction is 6-phosphogluconate dehydrogenase and its essentially irreversible because decarboxylations release carbon dioxide.

03:55 and the carbon dioxide goes away.

03:57 So that the process can’t be reversed very well.

04:00 A deficiency of this enzyme is harmful to red blood cells.

04:04 And so, this is very important reaction to be functioning if we want to have regular healthy supply of red blood cells.

04:10 There are two possible fates of this molecule, one is at this point the pathway gets a little bit more complicated.

04:16 In this reaction we see ribulose-5-phosphate being converted into ribose-5-phosphate.

04:21 Now, this reaction is a fairly simpler.

04:24 and we see the ribulose-5-phosphate on the left is a ketose meaning it has a ketone of bonded carbon number two.

04:30 The reaction converts the ketose on the left into an aldose on the right.

04:36 The aldose being ribose-5-phosphate with this aldehyde group on carbon number one.

04:40 The reaction is fairly simple and the enzyme involve that catalyzes the reaction is known as ribulose-5-phosphate isomerase.

04:47 Now, this reaction is very important for nucleotide metabolism as I’ve said I think three times now because of the importance of having the sugar Is the only source of the sugar for making nucleotides inside of the cell.