Fructose 6-phosphate biosynthesis

Since D-fructose and D-glucose phosphates are amongst the first products of photosynthesis, and since starch (in plants) and glycogen (in animals) are converted by phosphorylase to D-glucosyl phosphate, biosynthesis of carbohydrates revolves around these ubiquitous compounds... 

This enzyme interconverts ribulose-5-P and ribose-5-P via an enediol intermediate (Figure 23.30). The reaction (and mechanism) is quite similar to the phosphoglucoisomerase reaction of glycolysis, which interconverts glucose-6-P and fructose-6-P. The ribose-5-P produced in this reaction is utilized in the biosynthesis of coenzymes (including N/ DH, N/ DPH, F/ D, and Big), nucleotides, and nucleic acids (DNA and RNA). The net reaction for the first four steps of the pentose phosphate pathway is... 

One of the later steps in glucose biosynthesis is the isomerization of fructose 6-phosphate to glucose 6-phosphate. Propose a mechanism, using acid or base catalysis as needed. 

Both the aldol and reverse aldol reactions are encountered in carbohydrate metabolic pathways in biochemistry (see Chapter 15). In fact, one reversible transformation can be utilized in either carbohydrate biosynthesis or carbohydrate degradation, according to a cell s particular requirement. o-Fructose 1,6-diphosphate is produced during carbohydrate biosynthesis by an aldol reaction between dihydroxyacetone phosphate, which acts as the enolate anion nucleophile, and o-glyceraldehyde 3-phosphate, which acts as the carbonyl electrophile these two starting materials are also interconvertible through keto-enol tautomerism, as seen earlier (see Section 10.1). The biosynthetic reaction may be simplihed mechanistically as a standard mixed aldol reaction, where the nature of the substrates and their mode of coupling are dictated by the enzyme. The enzyme is actually called aldolase. 

In Box 10.4 we saw that an aldol-like reaction could be used to rationalize the biochemical conversion of dihydroxyacetone phosphate (nucleophile) and glyceraldehyde 3-phosphate (electrophile) into fructose 1,6-diphosphate by the enzyme aldolase during carbohydrate biosynthesis. The reverse reaction, used in the glycolytic pathway for carbohydrate metabolism, was formulated as a reverse aldol reaction. 

N-acetylglucosamine (see Chapter 9) is a component of glycoproteins, connective tissue proteoglycans, and complex lipids. It may be synthesized in the human organism from fructose-6-phosphate, as indicated in Figure 18.17. N-acetylglucosamine is also a precursor of N-acetylmannosamine, which along with pyruvic acid participates in the biosynthesis of sialic acid. 

Primary amine catalysis (usually involving a lysine residue) has been recognised to play an important role in various enzyme-catalysed reactions. Examples are the conversion of acetoacetate to acetone catalysed by acetoacetate decarboxylase, the condensation of two molecules of S-aminolevulinic acid catalysed by -aminolevulinic deshydratase during the biosynthesis of porphyrins, and the reversible aldol condensation of dihydroxy-acetone phosphate with glyceraldehyde which in the presence of aldolase yields fructose-1-phosphate (64) (For reviews see, for example, Snell and Di Mari,... 

Fig. 8.4 The glycolysis pathway in Saccharo-myces and the biosynthesis of ethanol and glycerol. Compounds DHAP, dihydroxyl-acetone monophosphate Fru6P, D-fructose-6-phosphate Frul,6P2, D-fructose-1,6-bisphosphate GA3P, D-glyceraldehyde-3-phosphate GL3P, sn-glycerol-3-phosphate GLAP2, phosphoglycerate-3-phosphate ...

Fig. 1. The reductive pentose phosphate cycle (RPP). The solid lines indicate reactions of the RPP cycle. The number of lines per arrow indicates the number of times each reaction occurs for one complete turn of the cycle in which three molecules of COj are converted to one molecule of G3P. Each reaction of the cycle occurs at least once. The double dashed lines indicate the principal reactions removing intermediate compounds of the cycle for biosynthesis. Abbreviations RuBP, ribulose 1,5-bis-phosphate PGA, 3-phosphoglycerate DPGA, 1,3-diphosphoglycerate, FBP, fructose 1,6-bisphos-phate F6P, fructose 6-phosphate SBP, sedoheptulose 1,7-bisphosphate S7P, sedoheptulose 7-phosphate Xu5P, xylulose 5-phosphate R5P, ribose 5-phosphate Ru5P, ribulose 5-phosphate TPP, thiamine pyrophosphate. From Ref. 1.

When NADPH levels are high, the reversible nonoxidative portion of the pathway can be used to generate ribose 5-phosphate for nucleotide biosynthesis from fructose 6-phosphate and glyceraldehyde 3-phosphate. 

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