Biochemistry of carbohydrates/ pentose phosphate pathway الفريق الطبي األكاديمي

Transcription

1 Biochemistry of carbohydrates/ pentose الفريق الطبي األكاديمي Done By: - Khansaa Mahmoud - Renad Aburumman لكية الطب البرشي البلقاء التطبيقية / املركز /

2 Biochemistry of carbohydrates/ pentose **This topic starts from the minute (07:30) of the record, what was previously said, is a revision of the previous lectures. The pentose is called sometimes as PPP, or hexose monophosphate shunt. It is not considered a metabolic pathway because it has no start nor end; it is an intersection of a set of metabolic reactions, it is a multistep reactions interacting with each other, so you are not going to memorise this intersection pathway but you have to understand the segnifience and physiologic importance of this pathway. Here you see about 10 structures, all of them will participate in this pathway. (You are not supposed to memorize their structures, except those who are familiar to you, glucose for example). Some of these sugars are hexoses, pentoses, ketoses and aldoses; they are intermediates pf the PPP. Page 1

3 The number in the figure are the indicators of enzymes, you are not supposed to memorize them too. PPP use glucose-6-phosphate that comes from -glycogen. -the phosphorylation of glucose. -Originate from fructose or galactose. This compound (glucose-6-phosphate) is oxidized with a catalyst enzyme, called glucose-6-phosphate dehydrogenase. (This enzyme must be memorized, because some chemical problems may occur when it is deficient in cells, they are called glucose-6-phosphate deficiency diseases). Page 2

4 In this step, the glucose-6-phosphste is oxidized by the enzyme glucose-6- phosphate dehydrogenase, and it uses -as coenzyme- NADP +. You usually deal with NAD as a coenzyme, but this enzyme (G-6-P dehydrogenase) uses NADP. *As a summary: NADP coenzyme that is used by G6Pdehydrogenase to oxidize glucose-6-phsphate to 6- phosphogluconic acid(6pg). **The important thing here is the production of NADPH, which is very important molecule for the biosynthesis reactions, so the source of NADPH is the PPP (the conversion of G-6-P to 6-phosphgluconic acid by the enzyme G-6-P dehydrogenase ), NADPH is very important for the fatty acids biosynthesis. Fatty acids synthase and other enzymes use NADPH as a coenzyme. Page 3

5 As a summary: Oxidation of glucose-6-phosphate to 6-phosphocluconic acid then to and production of NADPH, how many NADPH in the oxidation stage are produced? Two NADPH molecules because there are two oxidation reactions(one from G6P 6-PG/the other one from 6-PG Ru-5- P). Page 4

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7 The second feature what you have to understand and memorize is the isomerization. From the first stage riboluse-5 phosphate(ru-5-p) is produced and this could be isomerized to Xu5 phosphate or ribose 5 phosphate (R-5-P). Ru-5-P(ketone) R-5-P(aldehyde) is an important step because it's produce R-5-P &the importance of producing ribose 5 phosphate that it is used in the synthesis of DNA and RNA(nucleotide metabolism) because they contain a pentose sugar that is ribose 5 phosphate. So where do we get the ribose sugar to synthesis of nucleotides from? We get it from the pentose, the isomerization of ribulose-5-phosphate to ribose-5-phosphate. What are the components of nucleotides? *Nitrogenous base *phosphate group *Ribose sugar, what is it? Pentose sugar, what is it is source? Isomerization of ribulose. Where does it come from? From the dehydrogenation of glucose-6-phosphate. Page 6

8 Biochemistry of carbohydrates/ pentose Page 7

9 The third feature of the PPP is the carbon rearrangement (minute 21:00) Here you see ribose 5 phosphate, Xu-5-phosphate, glyceraldehyde-3- phosphate, S-7-P, fructose-6-phosphate, E-4-P. All of these are sugars you are not supposed to memorize their names and structures, but you have to understand them.) These sugars - you see- some of them are composed of 7 carbon atoms some are composed of six carbon atoms, Some have three carbon atoms some with four carbon atoms. so in this stage there is a rearrangement between the sugar in which they give different types of sugars, by enzymes that will arrange or do some reactions to produce different types of sugars. The importance of this for the E-4-P(compose of 4 C atoms) sugar it is essential precursor synthesis of aromatic amino acids like phenylalanine, tryptophan and tyrosine,in order to synthesis these important amino acids in our bodies E-4-P is required. From where do we get this sugar? From the rearrangement of carbons. (To see that clearly in details check slides 7 + 9) This is one imp. thing about carbon rearrangement, another important one fructose-6-phosphate and glyceraldehyde-3-phosphate, where did you see those molecules (sugars) took places as intermediates? In glycolysis. So supposedly, you have shortage in these intermediates pentose provides these intermediates for the glycolysis to be continued, and this another physiological importance of PPP in carbon rearrangement is providing intermediates for the glycolysis and gluconeogenesis. As a summary: The importance of the pathway is: 1. production of NADPH, in the oxidation stage, important for biosynthetic reactions such as fatty acids synthesis. 2. Provides ribose-5-phosphate, for nucleotide synthesis, in the Page 8

10 isomerization stage. 3. Carbon rearrangement. *to provide intermediates for glycolysis and gluconeogenesis and *precursors for aromatic amino acid synthesis tryptophan, tyrosine and phenylalanine. The sugar that is the precursor is E-4-P. Why this pathway is called pentose not Hexose, as long as the sugars are Hexoses not pentoses? Because the pentoses are the most important sugars among the others, to produce nucleotides for nucleic acids. This pathway also has other names as mentioned before. So this pathway is multifunctional not directional like conventional pathways such as *glycolysis (from glucose to pyruvate) and gluconeogenesis (from pyruvate to glucose), or *oxidation of fatty acids (from fatty acid to acetyl co a). So it is a multifunctional pathway producing different molecules according to * the need of the cell and *the availability of substrates. (32:54) quick summary: The importance of oxidation stage is production of NADPH; it produces two molecules of NADPH through two reactions. The first is the Page 9

11 conversion of glucose-6-phosphate to 6-phosphoglugonic acid, and the second one is the conversion of 6-phosphoglugonic acid to riboluse-5- phosphate. The importance of producing NADPH is that it contributes biosynthesis fatty acids. The importance is isomerization is producing ribose-5-phosphate, the importance of ribose-5- phosphate is the synthesis of nucleotides which contributes nucleic acids synthesis. The importance of carbon rearrangement is producing different sugars, (fructose-6-phosphate and glyceraldehyde-3-phosphate which are used in glycolysis and gluconeogenesis) and (E-4-P which is used an automatic amino acids synthesis such as tyrosine, phenylalanine and tryptophan). (Slides 8 + 9) R-5-P and Xu-5-P both have five carbon atoms and 5+ 5=10, which equals 3 + 7, which are S-7-P and GLAYAL-3-phsphate. Two Sugars, which one is five carbon atoms,converted to Sugars one of them 7 and 3 carbon atoms. This is the carbon rearrangement. How does that happen? By the enzyme transketonase (memorize its name), the portion of CH2OOH from the Xu-5-P is taken to produce heptolose. It took two carbon atoms adding them to the 5 atoms of R-5-P to give S-7-P, the left three carbon atoms are converted to glyceraldehyde-3- phosphate, and which is important in glycolysis. Then those products would be rearranged to give 4 and 6 carbon atoms sugars which are fructose-6-phosphate (used in glycolysis) and E-4-P (used as a precursor for automatic amino acid synthesis). Heptolose + triose will be converted to hexose + pentose. The enzyme used is called Transaldolase because it transfers an aldehyde group. (Memorize the enzymes name). Thank you Page 10