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Glucose-6-phosphate dehydrogenase, G6PD, G6PD deficiency is the most common enzyme deficiency, so G6PD is a big deal. But you cannot understand what's disease before first understanding what's normal. So in this video, we'll just discuss the enzyme glucose-6-phosphate dehydrogenase. In the next video, we will discuss G6PD deficiency, also historically known as favism. But first, to get an idea of G6PD deficiency, let's go back to your biochemistry in glycolysis, where glucose will become pyruvate down the road. Now we have glucose, thanks to hexokinase. Now we have glucose-6-phosphate. Glucose-6-phosphate will be converted into fructose-6-phosphate. This is the normal glycolysis, but there is a shunt called hexose monophosphate shunt, or HMP shunt. Why shunt? To form this amazing compound, NADPH. So thanks to the enzyme G6PD, now the glucose-6-phosphate will be converted into 6-phosphogluconate. The 6-phosphate locally can go back into glycolysis through the fructose-6-phosphate step and go down until we have the nice pyruvate. Why shunt? To form this compound. So without G6PD, there is no NADPH. NADPH is the reduced form of the oxidized NADP. Again, without G6PD, there is no NADPH. But what's the big deal? Why is NADPH so important? This is the story.
Morning Glory. Here you have something called the redox metabolism in the red blood cell. Redox is what? Is the reduction of a compound called glutathione. Glutathione here is oxidized. When glutathione is reduced, we are extremely happy. So this is reduced glutathione. Okay, why do I care? Because reduced glutathione will protect the red blood cell from the evil free radical. Do you remember the Fenton reaction? When Fe is left free by Fenton reaction, it will produce free radicals, and these free radicals will destroy the cell. So I want to say that the reduced glutathione is a protective mechanism against destruction of the red blood cell by the nasty free radical. So when glutathione is reduced, now I can reduce the free radical into water. The hydroxyl free radical will be converted into water. Harmful is converted into harmless only when the glutathione is reduced. Fine. To reduce glutathione from its oxidative state or oxidized state, we need this amazing compound again, the NADPH. When NADPH is in the reduced form, in the aged form, we are so happy because now this reduced NADPH, H is reduction, it can pass this reduction into the glutathione to reduce it. Fine. Does this sound familiar? Glucose-6-phosphate to 6-phosphogluconate by G6PD, and by the same token, the NADP is converted into NADPH. Yes, this was the HMP shunt from the previous slide. So again, we have HMP shunt where the glucose-6-phosphate will be converted into 6-phosphogluconate. Thank you, G6PD. By the same token, in the exact same step, NADP is reduced into NADPH. I'm so happy. Yes, I am. Why? Because NADPH is reduced. Oxygen oxidizes; hydrogen reduces. This is a reduced form, and now we can reduce the glutathione from oxidized glutathione into reduced glutathione. Are you happy? Of course, I'm happy. Why? Because those evil bad free radicals are now destroyed by converting the hydrox, the hydrogen peroxide free radical into harmless water. So now the red blood cell is happy because the devil is not coming because glutathione, or reduced glutathione, is protecting the red blood cell. The red blood cell is so happy. The red blood cell will never be happy without the NADP. There is no NADPH without the G6PD. That's why G6PD is a big deal.
Now let's talk a little bit about oxygen free radicals. Free radicals are bad for your body, yes, because they can damage your red blood cells, but they can be good if they will damage the bacteria. So first, let's get to the normal state. Here we have oxygen. When we reduce oxygen by adding an electron, since an electron has a negative charge, it will reduce; it will not oxidize; it will cause reduction of the oxygen into a superoxide. Negative means reduction. This is the electron. Can we add another electron? Another partial reduction? Yes. Now we have the hydrogen peroxide. Please reduce it more by adding another electron. Now we have hydroxyl free radical. Another partial reduction, and now we have water. All of this amazing, nice steps occur in the electron transport chain, and this is completely normal. Are you happy? Yes, because water is harmless. However, these three compounds are free radicals, which are, if they are left alone and their free radical status, they can damage ourselves, which is really bad. Okay, but since they can damage cells, why not damage bacteria for us so that we can, they can be useful. This is why the neutrophils are extremely lucky to have these hydroxyl free radicals. So the oxygen will be converted into superoxide by an enzyme called NADPH oxidase, and it will use the amazing compound, the NADPH. Fine. NADPH is getting oxidized, hence NADPH oxidase. By the same token, oxygen is being reduced into superoxide because we have said that the superoxide is a reduced form of the oxygen because we have added an electron. Electron, negative charge. Superoxide is a reduced form of the oxygen. Okay. Another enzyme called superoxide dismutase will convert the superoxide into hydrogen peroxide. We can then use the hydrogen peroxide by the enzyme myeloperoxidase to form something called hypochlorite. This hypochlorite will damage the nasty bacteria, and white blood cells are heroes. Fine. So NADPH is necessary for the white blood cells to kill bacteria. True. And there is no NADPH without the G6PD enzyme. That's why G6PD is a big deal.
So in brief, glycolysis, we have glucose-6-phosphate. HMP shunt through the enzyme G6PD. Now we have the NADPH, and it's reduced form. NADPH will reduce the glutathione. The glutathione will reduce the hydrogen peroxide, which is harmful, into water, which is harmless. This is the great compound, NADPH. There is no NADPH if there is no G6PD. This is father, this is son, this is number one. So what's the function of NADPH? One, protect the cells from free radicals, especially hydrogen peroxide. Function number two, we have a lot of oxidative agents or stressors in our bodies, such as fava beans, for example, or maybe sulfa drugs. These stressors are bad. Why? Two reasons. They can produce free radicals to damage our cells, or they can convert the normal hemoglobin into methemoglobin by oxidizing the ferrous into ferric iron. Fine. How to protect ourselves from the oxidative agents? The amazing compound called NADPH. It protects us from the both of the weapons of the oxidative agents by protecting us from the free radicals and by converting the methemoglobin back into the normal hemoglobin. Wow, NADPH is amazing. Wait, there is more. Function number three, it can convert the oxygen into superoxide to kill the ugly bacteria. Oh wow, how wonderful is the NADPH. But please remember, there is no NADPH without G6PD. That's why G6PD is a big deal. That's it for today. Next video, we will discuss G6PD deficiency, the most common enzyme deficiency in the world. That's why when your medical school would like to test you about enzymes, guess which enzyme they will test you on? G6PD, because it's a big deal.