Sugar Metabolism Pathways Quiz

Sugar Metabolism Pathways

• Diet includes fructose, glucose, and galactose
• Glucose is used in glycolysis
• The body needs other pathways to metabolize the other sugars in the diet

Fructose Metabolism

• Fructose is found in the diet as a free form or in sucrose
• Also produced by the polyol pathway in the eyes
• Fructose converts to a glycolytic intermediate for ATP generation
• The liver is the most important organ for fructose metabolism
• Fructose can account for 30-60% of the dietary carbohydrate intake

The Polyol Pathway

• The polyol pathway converts unused glucose into fructose in two steps:
  • Aldolase reductase converts glucose to sorbitol
  • Sorbitol dehydrogenase converts sorbitol to fructose
• This pathway produces fructose from unused glucose.
• This pathway contributes to cataracts, especially in diabetics, due to high glucose concentrations and sorbitol build-up

Fructose Metabolism Steps

• Fructose is converted to fructose-1-phosphate (F-1-P) using fructokinase (costs ATP)
• F-1-P is then converted to glyceraldehyde and DHAP (discussed in previous slide) via aldolase B enzyme
• Glyceraldehyde is converted to glyceraldehyde-3-phosphate and DHAP entering the glycolytic pathway via triose kinase (ATP needed)
• Aldolase B in the liver has dual functions with different substrates: (F16P for glycolysis and F1P for fructose metabolism)

Galactose Metabolism

• Galactose is primarily from lactose in milk.
• Galactose is converted to galactose-1-phosphate by galactokinase (costs ATP)
• Galactose-1-P reacts with UDP-Glucose and forms UDP-Galactose and Glucose-1-P via galactose-1-P uridyltransferase enzyme
• G1P is converted to G6P, to enter glycolysis pathway or be excreted into the glycogen pathway

Pentose Phosphate Pathway

• The pentose phosphate pathway is a detour from glycolysis
• G6P is a substrate for the pentose phosphate pathway (also a part of glycolysis and glycogen formation)
• Oxidative part of the pathway generates NADPH (reducing equivalents)
• NADPH is then used in other pathways
• In the non-oxidative part, 5-carbon sugars are converted to glycolysis intermediates (like F6P and G3P) or are used in nucleotide synthesis.
• It bypasses glycolysis to generate NADPH and 5-carbon sugars.

Oxidative Part of the Pentose Phosphate Pathway

• Contains 3 steps
  • Glucose-6-phosphate dehydrogenase converts G6P to 6-Phosphoglucono-δ-lactone, producing NADPH
  • Gluconolactonase adds an OH group to the 5 carbon (C5)
  • 6-phosphogluconate dehydrogenase converts 6-phosphogluconate to ribulose-5-phosphate producing NADPH

Epimerization Step

• Ribulose-5-phosphate is converted to xylulose-5-phosphate via epimerase
• Changes the stereochemical position of the OH
• Products are used to form glycolysis intermediates or nucleotides

Transketolase

• Transketolase converts two 5-carbon sugars (2XC5) into a 3-carbon sugar (C3) and a 7-carbon sugar (C7)
• Uses a thiamine pyrophosphate coenzyme
• If G3P (a glycolysis intermediate) is present, then what to do with sedoheptulose-7-phosphate?
• Answer: Add another reaction step.

Transaldolase

• Transaldolase converts C3 and C7 into C4 and C6 sugars

Net Reactions of the Pentose Phosphate Pathway

• 3 Glucose-6-P produces 6 NADPH (in oxidative rxn) and 3 CO2
• 3 Glucose-6-P can also produce 2 Fructose-6-P, glyceraldehyde-3-P and other glycolytic intermediates
• No oxidation/reduction reactions occur in the non-oxidative part

Pathways That Require NADPH

• Detoxification (e.g., reducing oxidized glutathione), cytochrome P450 monooxygenases
• Reductive synthesis (e.g., FA synthesis, cholesterol synthesis, neurotransmitter synthesis, nucleotide synthesis, superoxide synthesis)

Hemolysis

• Loss of pentose phosphate pathway leads to lack of NADPH
• Lack of NADPH leads to lack of reduced glutathione
• Lack of reduced glutathione leads to high levels of peroxide and oxygen stress, causing hemolysis
• Heinz bodies, and cross-linked Hb can also lead to mechanical stress.

Control of Pentose Phosphate Pathway

• Cellular needs dictate the direction of the pentose phosphate pathway
• NADPH only = oxidative reactions to produce NADPH
• NADPH + ribose-5-P = oxidative reactions for NADPH, and isomerase for ribulose-5-P to ribose-5-P
• Ribose-5-P only = only nonoxidative reactions
• NADPH and pyruvate = both oxidative and nonoxidative reactions.

Test your knowledge on sugar metabolism pathways including glycolysis, fructose metabolism, and the polyol pathway. Understand how different sugars like fructose, glucose, and galactose are processed in the body, their dietary significance, and the implications of these pathways for health, particularly in relation to diabetes.