Metabolism of monosaccharides and disaccharides Metabolism of fructose

Metabolism of monosaccharides and disaccharides

Metabolism of fructose • The major source of fructose is the disaccharides sucrose. • It is also found in fruits, honey, corn syrup • the entry of fructose into cells is not insulindependent (unlike glucose), and in contrast to glucose, fructose does not promote the secretion of insulin. • Liver is the main site of fructose metabolism. – Fructose breakdown – Fructose formation

Reaction of fructose breakdown • Fructose is phosphorylated to F-1 -P by fructokinase in the liver • F-1 -P is cleaved by liver aldolase (aldolase-B) to dihydroxy acetone phosphate (DHAP) and glyceraldehyde. • Glyceraldehyde is phosphorylated by glyceraldehyde kinase to glyceraldehyde-3 phosphate – According to the metabolic status of the tissue, these two triose phosphate (DHAP and GA-3 -P) enter the glycotic pathway, gluconeogenesis and glycogenesis.

Reaction of fructose breakdown (count’d) • In extrahepatic tissue, especially the adipose and muscle tissues, fructose can be phosphorylated by hexokinase to F-6 -P. • However, this is a slow reaction occurs in the presence of high concentration of fructose because when fructose is present with glucose, its phosphorylation is inhibited by glucose

Metabolic pathway of fructose In Liver Diet In extrahepatic tissues Hexokinase D-Fructose F-6 -P Glycogenesis Glycolysis Fructokinase ATP D-Glyceraldehyde Glucose Fructose -6 - P Fructose -1 - P Aldolase-B Glycogen Fructose -1, 6 - P Dihydroxyacetone phosphate Triokinase ATP Aldolase -A (all tissues) Aldolase –B (in liver) Glyceraldehyde-3 -Phosphate Glycolysis Glycerol Pyruvate Glycerol-3 -P Acetyl-Co. A Triacylglycerol synthesis Fatty acid, cholesterol

Sorbitol or polyol pathway formation of fructose • Sorbitol or polyol pathway is formation of fructose from glucose – Aldose reductase reduce glucose to sorbitol. • this enzyme is found in many tissues as lens, retina, peripheral nerve cells, kidney, placenta, RBC, ovaries but it is not found in liver – In the cells of liver, ovaries and sperm cells, there is a second enzymes, sorbitol dehydrogenase that can oxidise the sorbitol to produce fructose – The pathway from sorbitol to fuctose in the liver provides a mechanism by which dietary sorbitol is converted into fructose which can enter glycolysis

Sorbitol or polyol pathway NAD+ NADH + H+ NAD+ β-D-glucose Aldose reductase D-Sorbitol NADH + H+ Srbitol dehydrogenase β-D-Fructose

Galactose metabolism • The major dietary source of galactose is lactose obtained from milk and milk product • Some galactose can also be obtained by lysosomal degradation of complex carbohydrates such as glycoproteins and glycolipids, which are important membrane components • Like fructose, the entry of galactose into cells is not insulin-dependent • Galactose is ready converted in the liver to glucose

Reaction of the pathway • The first reaction in galactose metabolism in the liver is phosphorylation of galactose to galactose -1 - phosphate by the enzyme galactokinase, using ATP as [phosphate donor • Galactose-1 - phosphate reacts with UDP-glucose to form UDP-galactose and glucose-1 - phosphate, catalyzed by galactose-1 -phosphate uridyl transferase • The conversion of UDP-galactose to UDP-glucose catalysed by an UDP-galactose-4 -epimerase. – Epimeraization involves an oxidation and reduction at carbon 4 with NAD as a coenzyme • Finally, glucose released from UDP-glucose after conversion to G-1 -P via formation of glycogen by glycogenesis followed by glycogenolysis

Pathway for conversion of galactose to glucose in the liver Galactose ATP ADP Glycogenesis Glycogen Mg+ Galactokinase Galactose-1 -phosphate uridyl transferase Glycogenolysis UDP-Glucose-6 -P UDP-Galactose-4 -epimerase Glucose-1 -phosphate UDP-Galactose

Metabolism of mannose • Mannose, the C-2 epimer of glucose is an important component of glycoproteins. • Hexokinase phosphorylate mannose, producing mannose -6 -phosphate which is isomerised to F-6 -P by phosphomannose isomerase

Conversion of mannose to fructose 6 phosphate Mannose Hexokinase ATP Mannose-6 -phosphate Phosphomannose isomerase Fructose-6 -phosphate