Question

write a balanced equation for HMP pathway whereby Fruc-6-P and Gly 3-P generated by each passage through HMP is catabolized by glycolysis and TCA cycle to NADH and CO2?
(minimum input will be three glucose-6-p)

Answer 1

In order to break the question up, this is basically a Glycolytic pathway. I will try explaining it as clearly as possible with the equation and the process of achieving the equation.

To begin with,

The Glycolytic Pathway

In glycolysis, a pathway with 10 reactions, each glucose molecule is converted into two pyruvate molecules. In addition, two molecules each of ATP and NADH are produced. Reactions with double arrows are reversible reactions, and those with single arrows are irreversible reactions that serve as control points in the pathway

The Reactions of the Glycolytic Pathway

Glycolysis is summarized in the diagram below The 10 reactions of the glycolytic pathway are as follows.

1. Synthesis of glucose-6-phosphate. Immediately after entering a cell, glucose and other sugar molecules are phosphorylated. Phosphorylation prevents transport of glucose out of the cell and increases the reactivity of the oxygen in the resulting phosphate ester. Several enzymes, called the hexokinases, catalyze the phosphorylation of hexoses in all cells in the body. ATP, a cosubstrate in the reaction, is complexed with Mg2. (ATP-Mg2 complexes are common in kinase-catalyzed reactions.) Under intracellular conditions the reaction is irreversible; that is, the enzyme has no ability to retain or accommodate the product of the reaction in its active site, regardless of the concentration of G-6-P.

2. Conversion of glucose-6-phosphate to fructose-6-phosphate. During reaction 2 of glycolysis, the open chain form of the aldose glucose-6-phosphate is converted to the open chain form of the ketose fructose-6-phosphate by phosphoglucose isomerase (PGI) in a readily reversible reaction:

Recall that the isomerization reaction of glucose and fructose involves an enediol intermediate . This transformation makes C-1 of the fructose product available for phosphorylation. The hemiacetal hydroxy group of glucose-6-phosphate is more difficult to phosphorylate.

3. The phosphorylation of fructose-6-phosphate. Phosphofructokinase-1 (PFK-1) irreversibly catalyzes the phosphorylation of fructose-6-phosphate to form fructose-1,6-bisphosphate:*

The PFK-1-catalyzed reaction is irreversible under cellular conditions. It is, therefore, the first committed step in glycolysis. Unlike glucose-6- phosphate and fructose-6-phosphate, the substrate and product, respectively, of the previous reaction, fructose-1,6-bisphosphate cannot be diverted into other pathways. Investing a second molecule of ATP serves several purposes. First of all, because ATP is used as the phosphorylating agent, the reaction proceeds with a large decrease in free energy. After fructose-1,6-bisphosphate has been synthesized, the cell is committed to glycolysis. Because fructose-1,6-bisphosphate eventually splits into two trioses, another purpose for phosphorylation is to prevent any later product from diffusing out of the cell because charged molecules cannot easily cross membranes.

4. Cleavage of fructose-1,6-bisphosphate. Stage 1 of glycolysis ends with the cleavage of fructose-1,6-bisphosphate into two three-carbon molecules: glyceraldehyde-3-phosphate (G-3-P) and dihydroxyacetone phosphate (DHAP). This reaction is an aldol cleavage, hence the name of the enzyme: aldolase. Aldol cleavages are the reverse of aldol condensations, described on p. xxx. In aldol cleavages an aldehyde and a ketone are products.

Although the cleavage of fructose-1,6-bisphosphate is thermodynamically unfavorable , the reaction proceeds because the products are rapidly removed.

5. The interconversion of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Of the two products of the aldolase reaction, only G-3-P serves as a substrate for the next reaction in glycolysis. To prevent the loss of the other three-carbon unit from the glycolytic pathway, triose phosphate isomerase catalyzes the reversible conversion of DHAP to G-3-P:*

After this reaction, the original molecule of glucose has been converted to two molecules of G-3-P.

6. Oxidation of glyceraldehyde-3-phosphate. During reaction 6 of glycolysis, G-3-P undergoes oxidation and phosphorylation. The product glycerate-1,3-bisphosphate, contains a high-energy phosphoanhydride bond, which may be used in the next reaction to generate ATP:

This complex process is catalyzed by glyceraldehyde-3-phosphate dehydrogenase, a tetramer composed of four identical subunits. Each subunit contains one binding site for G-3-P and another for NAD, an oxidizing ogent. As the enzyme forms a covalent thioester bond with the substrate , a hydride ion (H:) is transferred to NAD in the active site. NADH, the reduced form of NAD, then leaves the active site and is replaced by an incoming NAD. The acyl enzyme adduct is attacked by inorganic phosphate and the product leaves the active site.

7. Phosphoryl group transfer. In this reaction ATP is synthesized as phosphoglycerate kinase catalyzes the transfer of the high-energy phosphoryl group of glycerate-1,3-bisphosphate to ADP:

Reaction 7 is an example of a substrate-level phosphorylation. Because the synthesis of ATP is endergonic, it requires an energy source. In substratelevel phosphorylations, ATP is produced by the transfer of a phosphoryl group from a substrate with a high phosphoryl transfer potential (glycerate-1,3-bisphosphate) (refer to Table 4.1) to produce a compound with a lower transfer potential (ATP) and therefore G 0. Because two molecules of glycerate-1,3-bisphosphate are formed for every glucose molecule, this reaction produces two ATP molecules, and the investment of phosphate bond energy is recovered. ATP synthesis later in the pathway represents a net gain.

8. The interconversion of 3-phosphoglycerate and 2-phosphoglycerate. Glycerate-3-phosphate has a low phosphoryl group transfer potential. As such, it is a poor candidate for further ATP synthesis (G for ATP synthesis is –30.5 kJ/mol). Cells convert glycerate-3-phosphate with its energy-poor phosphate ester to phosphoenolpyruvate (PEP), which has an exceptionally high phosphoryl group transfer potential. (The standard free energies of hydrolysis of glycerate-3- phosphate and PEP are 12.6 and 61.9 kJ/mol, respectively.) In the first step in this conversion (reaction 8), phosphoglycerate mutase catalyzes the conversion of a C-3 phosphorylated compound to a C-2 phosphorylated compound through a two-step addition/elimination cycle.

IMAGE SOURCE MY TEXTBOOK

Glyceraldehyde-3-Phosphate Dehydrogenase Reaction In the first step the substrate, glyceraldehyde-3-phosphate, enters the active site. As the enzyme catalyzes the reaction of the substrate with a sulfhydryl group within the active site (step 2), the substrate is oxidized (step 3). The noncovalently bound NADH is exchanged for a cytoplasmic NAD (step 4). Displacement of the enzyme by inorganic phosphate (step 5) liberates the product, glycerate-1, 3-bisphosphate, thus returning the enzyme to its original form.

9. Dehydration of 2-phosphoglycerate. Enolase catalyzes the dehydration of glycerate-2-phosphate to form PEP

PEP has a higher phosphoryl group transfer potential than does glycerate2- phosphate because it contains an enol-phosphate group instead of a simple phosphate ester. The reason for this difference is made apparent in the next reaction. Aldehydes and ketones have two isomeric forms. The enol form contains a carbon-carbon double bond and a hydroxyl group. Enols exist in equilibrium with the more stable carbonyl-containing keto form. The interconversion of keto and enol forms, also called tautomers, is referred to as tautomerization: This tautomerization is restricted by the presence of the phosphate group, as is the resonance stabilization of the free phosphate ion. As a result, phosphoryl transfer to ADP in reaction 10 is highly favored.

10. Synthesis of pyruvate. In the final reaction of glycolysis, pyruvate kinase catalyzes the transfer of a phosphoryl group from PEP to ADP. Two molecules of ATP are formed for each molecule of glucose.

The Reactions of Glycolysis In all there are 10 reactions in the glycolytic pathway. (a) In stage 1, reactions 1 through 5 convert glucose into glyceraldehyde-3-phosphate. Two ATP are consumed in state 1 for each glucose molecule. (b) In stage 2 reactions 6 though 10 convert glyceraldehyde-3-phosphate into pyruvate. In addition to pyruvate, the reactions of stage 2 also produce 4 ATP and 2 NADH per glucose molecule

PEP is irreversibly converted to pyruvate because in this reaction—the transfer of a phosphoryl group from a molecule with a high transfer potential to one with a lower transfer potential—there is an exceptionally large free energy loss . This energy loss is associated with the spontaneous conversion (tautomerization) of the enol form of pyruvate to the more stable keto form. The 10 reactions of glycolysis are illustrated in IMAGES UPLOADED. The Fates of Pyruvate In terms of energy, the result of glycolysis is the production of two ATPs and two NADHs per molecule of glucose. Pyruvate, the other product of glycolysis, is still an energy-rich molecule, which can yield a substantial amount of ATP. Whether or not further energy can be produced, however, depends on the cell type and the availability of oxygen. Under aerobic conditions, most cells in the body convert pyruvate into acetyl-CoA, the entry-level substrate for the citric acid cycle, an amphibolic pathway that completely oxidizes the two acetyl carbons to form CO2 and and the reduced molecules NADH and FADH2. (An amphibolic pathway functions in both anabolic and catabolic processes.) The electron transport system, a series of oxidation- reduction reactions, transfers electrons from NADH and FADH2 to O2 to form water. The energy that is released during electron transport is coupled to a mechanism that synthesizes ATP. Under anaerobic conditions, further oxidation of pyruvate is impeded. A number of cells and organisms compensate by converting this molecule to a more reduced organic compound and regenerating the NAD required for glycolysis to

• During glycolysis, glucose is converted to two molecules of pyruvate. A small amount of energy is captured in two molecules each of ATP and NADH.

• In anaerobic organisms, pyruvate is converted to waste products in a process called fermentation

. • In the presence of oxygen the cells of aerobic organisms convert pyruvate into CO2 and H2O.

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