A very good morning friends. Today we will discuss about an important topic and important short note in biochemistry that is HMP shunt. HMP shunt means Hexose Monophosphate shunt. So these are the other names for HMP shunt.
First one is the Pentose Phosphate Pathway. In this pathway there is generation of number of pentose sugar. That's why it is known as Pentose Phosphate Pathway. This is an alternative pathway for oxidation of glucose molecule. This is an alternative pathway to glycolysis and TCA cycle.
glucose undergoes oxidation and in glycolysis and TCA cycle it will give CO2. So this is an alternative pathway or shunt pathway that's why it is known as shunt pathway for oxidation of glucose in which glucose or glucose 6 phosphate through this pathway gives you CO2. and it is also known as monophosphate because as we have already seen that in glycolysis there is generation of number of bisphosphates but in this pathway there is generation of monophosphates that's why it is known as hexose monophosphate shard this is also known as decanes and horecar pathway then phosphogluconate it is an intermediate in this pathway that's why it is also known as phosphogluconate oxidative pathway. There are two important steps in this pathway.
First one is the oxidative step and second one is the non oxidative step. So oxidative step it mainly occurs in the liver, adipose tissue. Then adrenal cortex, testes, ovaries, lactating memory gland and erythrocytes. So liver, adipose tissue and RBCs. These are the main site for the oxidative phase of HM.
While non oxidative pathway it occurs in the all cells of the body. It deals with the synthesis of pentose sugars and these pentose sugars are ultimately required for the DNA and RNA synthesis. So it occurs in the all cells of the body.
So the starting molecule in the HMP shunt is the glucose 6 phosphate. So glucose 6-phosphate it is converted into 6-phosphogluconolactone. Lactose.
This is a rate limiting step in this pathway. It is by the enzyme glucose 6-phosphate dehydrogenase. So this is the main and rate limiting enzyme in this pathway.
It requires NADP. It requires NADP as a coenzyme and NADP is converted into NADPH plus HINs. So this is the first rate limiting step in the HMP shunt.
Then with the help of gluconolactone hydrolase. This 6-phosphogluconolactone, it is converted into 6-phosphogluconate. Then with the help of 6-phosphogluconate dehydrogenase. It is a NADP dependent reaction again. NADP it is converted into NADPH and H ions.
And there is liberation of CO2 through an intermediate. That is 3-keto-6-phosphogluconate. Through this intermediate by decarboxylation it is converted into ribulose. high phosphates. So these steps in the HMP shunt they are known as oxidative phase.
Oxidative phase. And it is important in the generation of NADPH. So this NADPH it is utilized for the reductive biosynthesis that is it is utilized for fatty acid synthesis, cholesterol synthesis and steroid synthesis.
So this pathway it is mainly in the liver and adipose tissue of course mainly in the liver and adipose tissue. Now coming to the non oxidative phase of this pathway. In the non oxidative phase this ribulose 5-phosphate It is epimerized with the help of epimerase. It gives xylulose 5-phosphate.
And on isomerization with the help of isomerase, it gives ribose 5-phosphate. This ribose 5-phosphate is precursor for the nucleotide synthesis that is inosine monophosphate which gives nucleotides. So it is important in DNA and RNA synthesis.
Now with the help of transketolase reaction which is thymine pyrophosphate dependent and RBC transketolase level is major to assess the thymine status of the body. So this is TPP dependent reaction transketolase in which there is transfer of 2 carbon from this xylulose 5-phosphate to the ribose 5-phosphate it leads to the generation of C-dohyptolose. 7-phosphate and glyceraldehyde 3-phosphate. Now with the help of trans aldolase reaction. There is transfer of 3 carbon from CetoHeptulose 7 phosphate that leads to the generation of Erythrose 4 phosphate and Fructose 6 phosphate.
This is a trans aldolase reaction. Again there is transketolase reaction in which this erythrox 4-phosphate condenses with xylulose 5-phosphate to form fructose 6-phosphate and glyceraldehyde 3-phosphate. There is formation of two molecules of glyceraldehyde 3-phosphate which gives ultimately fructose 6-phosphate. If you start from the glucose 6 phosphate there is utilization of 6 molecules of glucose 6 phosphate and the first carbon from each glucose 6 phosphate it is liberated as carbon dioxide. dioxide and 5 glucose 6 phosphates they are generated in the HMP shunt.
So there is liberation of 6 molecule of CO2 in the oxidative phase by oxidative decarboxylation which is catalyzed by 6-phosphogluconate dehydrogenase. Then this fructose 6-phosphate, if you start from the beginning, there is involvement of 6-glucose 6-phosphate, which gives you 6 molecule of ribulose 5-phosphate. which gives you 6 molecule of ribulose 5-phosphate. Then this gives 2 molecule of ribose 5-phosphate and 4 molecule of xylulose 5-phosphate.
Now this will give you 2 molecule of sideroheptulose 7-phosphate and 2 molecule of glycerol dead 3-phosphate. There is two molecule of erythrox 4-phosphate and two molecule of fructose 6-phosphate. Now this erythrox 4-phosphate combines with the two molecule of xylulose 5-phosphate. It gives two molecule of fructose 6-phosphate and two molecule of glyceraldehyde 3-phosphate.
So there is generation of this is the first. First and second here is the 2 plus 2, 4 plus 1, 5. So this 5 fructose 6 phosphates, they gives ultimately 5 molecule of glucose 6 phosphates. So there is regeneration of 5 molecule of glucose 6 phosphates. If you see the overall reaction, there is involvement of 6 molecule of glucose 6 phosphates.
plus 12 NAD, NADP plus 6 molecule of water. It will give you 5 molecule of glucose 6 phosphate plus 12 NADPH plus 12 H ions. Plus 6 CO2.
So this is also known as oxidative pathway for glucose. And 10% of glucose it is oxidized by this HM patient. And liver and RBCs.
Utilize 30% of glucose through the HMP shunt. Now coming to the importance of HMP shunt. In the HMP shunt you will get two important products.
The first one is the NADPH and second one is the pentose sugar. So pentose sugar it is utilized for the DNA and RNA synthesis. DNA RNA synthesis also utilized for the nucleotide synthesis for example ATP it is also required for FAD NAD coenzyme a synthesis now coming to the uses of NAD pH HMP shunt, it is a source of LADPH.
The another source is the malic enzyme. This is the main source of LADPH. It is required for the reductive biosynthesis of fatty acid, steroids and cholesterol. Then it has free radical scavenging action.
For this action you require superoxide dismutase, peroxidase and glutathione reductase. So it is important for the action of glutathione reductase which is a NADPH dependent enzyme. Then it functions as an antioxidant by scavenging the free radicals. And it is required for the bactericidal action of macrophages. It is required for the bactericidal action of macrophages.
Then third, it is important in maintenance of RBC membrane integrity. In the absence of this NADPHR if the level is decreases it leads to the hemolytic jaundice because it is required for the production of reduced glutathione. by glutathione reductase which is a NADPH dependent enzyme.
This reduced glutathione is responsible for maintenance of RBC membrane. And again this NADPH prevents the formation of methemoglobin. It keeps the iron in the ferrous state. So that's why it is important.
Then... It is important in maintaining the permeability, sorry, it is important in maintaining the transparency of lens. Transparency of lens. So, in this way, RDPH, it has number of functions.
It also required for the detoxification reaction, which is carried out by the side. cytochrome p450 enzyme system which is a hydrolyze it requires nadph for its action then coming to the clinical significance of this hmp shunt means disorders are diseases which are related to the hmp shunt the first important is the Glucose 6-phosphate dehydrogenase deficiency that is known as G6PD deficiency. As such it is an asymptomatic condition. But when oxidant drugs are given in the treatment.
For example, primacrine. or sulphur drug. Sulphur drug that is Sulf-Methoxazole. If these oxidants or some antipyretics that is acetamylide, if these drugs are given in the treatment, they increases the production of free radical. free radicals and as there is problem in G6 dehydrogenase deficiency it lead to the decrease in NADPH production which is required for the antioxidant functions and this free radical causes damage to the RBCs and that leads to the hemolytic anemia or hemolytic jaundice.
So, increased destruction of RBC. lead to the release of hemoglobin and hemoglobin heme degradation leads to the increased bilirubin in serum that leads to the jaundice. So this is the main enzyme regulatory enzyme of this pathway that is glucose 6-phosphate dehydrogenase deficiency lead to the G6PD deficiency which mainly after the administration of oxidant drugs that is bimethyl sulfetoxazole. fava beans and acetanilides that causes free radical formation, damages the membrane, lead to the hemolytic jaundice. Second important is the Transketolase activity related to the Transketolase activity that is Wernicke's Korsakoff syndrome.
This is in the alcoholic. In alcoholic there is decreased absorption of thymine. Also there is decreased conversion of thymine to thymine pyrophosphate. This is the active form of the thymine.
That leads to the functional deficiency of thymine pyrophosphate. And this main reaction affects the transketolase reaction which is involved in the HMP. So in this Varney case, Korsakoff's psychosis, there is... Different symptoms that is the pneumonic is GOA, MP, that is global confusion, ophthalmoplasia, ataxia, memory loss and psychosis. This is due to the decreased level of thymine.
pyrophosphate that affects mainly the pyruvate dehydrogenase complex and that lead to the decrease in the synthesis of ATP so this is all about the clinical significance of HMP shot Summarizing the all, this pathway is divided into two phases, oxidative and non-oxidative phase. It mainly occurs in the liver, adipose tissue and RBCs. It leads to the generation of NADPH and PET.
Pentose sugar is a precursor for the nucleotide synthesis involved in the DNA and RNA synthesis. NADPH is mainly involved in the reductive biosynthesis of fatty acids, steroids and cholesterol.