Sugar Metabolism Pathways Quiz

Study Notes

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 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 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

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.

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

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.

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

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

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.

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.