Chem*4520 Metabolic Processes
Fall Semester 2000
Modified August 2000
|schematic view of the enzyme citrate synthase,|
with bound acetyl-CoA analog in green
|Mon Sept 25|
Utilization of fructose, mannose and galactose; synthesis of N-acetyl glucosamine, glucuronic acid, rhamnose, fucose and N-acetyl-neuraminidate.
|Voet Chapter 16, pp.600-606,, 657-658.|
Mathews, Van Holde: Chapter 16 pp. 561-572.
Stryer Chapter 19, pp. 491-493.
None of the texts deal with synthesis of the modified monosaccharides, although these compounds are important components of glycoproteins, glycolipids and heteropolysaccharides.
The hexokinase of muscle and adipose tissue can accept fructose as a substrate, but KM is much higher for the furanose sugar than the usual pyranoses.
Liver contains the enzyme fructokinase:
Mannose is phosphorylated by hexokinase; a specific mannosephosphate isomerase yields fructose-6-P.
Pentoses such as ribose, ribulose, xylose and xylulose can be phosphorylated and are converted to triose phosphates by the non-oxidative rearrangements of the pentose phosphate pathway.
Galactose is derived from breakdown of lactose in the digestive tract. There is a specific galactokinase, which phosphorylates on C-1 rather than C-6. This allows for activation to UDP-galactose.
UDP-galactose and UDP-glucose can be interconverted by the enzyme 4-epimerase. This enzyme contains a tightly bound NAD+, and the 4-ketopyranose is formed as a intermediate which is then reduced without ever being released from the active site. The new hydroxyl is randomly generated with either glucose or galactose configuration.
= -30.5 kJ/mol for hydrolysis of the glycosyl-phosphate bond in UDP-sugars. This makes them suitable as glycosyl group donors. A variety of target-specific enzymes can transfer the glucosyl unit of UDP-sugars to an acceptor with a nucleophilic -OH, -NH or -SH group. (Some enzymes use ADP, GDP or even dTDP as the activating nucleotide, e.g. ADP-glucose in starch synthesis.)
for transfer to O is about -10 to -15 kJ/mol. Acceptors may include the non-reducing end of an existing polymer such as glycogen, and the transfer of glucose, e.g. by glycogen synthase, elongates the polymer by one unit, releasing UDP.
Glycoproteins, glycolipids and heteropolysaccharides often contain modified sugars in the chain, such as uronic acids, 6-deoxysugars, amino-sugars (usually as N-acetyl amides), N-acetylneuraminic acid (NANA, also known as sialic acid) in animals and N-acetylmuramic acid in bacterial cell walls.
UDP-galacturonate is formed by the action of 4-epimerase on UDP-glucuronate. A 5-epimerase converts UDP-D-glucuronate into UDP-L-iduronate, incorporated into the heteropolysaccharide dermatan sulfate.
Bacteria contain a variety of deoxy- and dideoxy sugars made by similar processes. In animal blood group oligosaccharides, GDP-fucose is made by a similar process starting from GDP-mannose.
N-Acetylneuraminic acid, found on cell surface glycolipids and glycoproteins, is made from N-Acetylmannose-6-P by condensation with PEP:
N-acetylneuraminic acid is activated by formation of a CMP derivative.
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