Minor pathways of hexose Flashcards
galactose metabolism
- Galactose –> galactose-1P; enzyme: galactokinase
- galactose 1P –> UDP-galactose; enzyme: galactose 1P uridyl transferase
- UDP-galactose –> UDP-glucose; enzyme: UDP-galactose-4-epimerase
- UDP-glucose can be used directly in glycogenesis or can be further converted to glucose-6P for glycolysis
classical galactosemia
defect in galatose 1P uridyl transferase enzyme prevents conversion from galactose 1P to UDP galactose.
UDP galactose
can be converted into UDP glucose or can be broken down into lactose, glycoproteins or glycolipids
aldose reductase
converts galactose to galactitol
fructose metabolism
- *metabolized in liver!
1. Fructose –> Fructose-1P; enzyme: fructokinase
2. fructose-1P –> DHAP and glyceraldehyde; enzyme: aldolase B
3. conversion of those products into glyceraldehyde-3P which can be converted to pyruvate through gluconeogenesis
fructose metabolism can cause transient decrease in phosphate in a cell because
fructokinase is not regulated, and has a much higher rate than aldolase B. Therefore, fructokinase can continue to phosphorylate fructose at higher rate than aldolase B can convert fructose-1P. Results in transient decrease in phosphate as it is tied to fructose.
defects in fructose or galactose metabolism that affect the first step result in
fructose and galactose cannot be phosphorylated in the cell, thus cannot be kept in cell. Excreted through urine.
**Can cause galactose to be converted to galactitol by aldose reductase, which can build up in eyes causing cataracts.
defects in fructose or galactose metabolism that affect the second step result in
buildup of the phosphorylated fructose or galactose. This results in trapped phosphate, low phosphate levels, decreased glycogenolysis, low ATP (high AMP), liver and kidney failure, hypoglycemia, lactic acidosis, increased uric acid
polyol pathway
glucose —aldose reductase–> sorbitol —sorbitol dehydrogenase—> fructose.
sorbitol dehydrogenase and diabetic pathology
sorbitol dehydrogenase is very low in retinal cells, neurons, and kidney tubules. With excessive blood glucose levels, more glucose is converted to sorbitol, but the sorbitol in those tissues cannot be converted to fructose. Thus, buildup of sorbitol in those tissues can cause diabetic retinopathy, peripheral neuropathy, and nephropathy.
pentose phosphate pathway (HMP shunt)
Provides mechanism to convert non-hexose sugars to hexose sugars. Occurs in the cytosol of every cell in the body, but is upregulated in highly proliferative cells.
-important metabolic byproducts: NADPH (electron donor for anabolic rxns, reducing agent for oxidative stress) and ribose-5-phosphate (nucleotide precursor)
transketolase
enzyme of the pentose phosphate pathway (HMP shunt) that requires thiamine coenzyme; its activity can be measured to determine thiamine status in the body
glucose-6P dehydrogenase (G6PD)
rate limiting enzyme of pentose phosphate pathway (HMP shunt); regulated by NADPH and G6P levels (inhibited by NADPH). Mutations result in severe NADPH deficiency especially in RBCs. Inherited on X chromosome.
Significance of HMP shunt in RBCs
RBCs lack a nucleus, and are exposed to the highest amount of oxidative stress due to production of superoxide and hydrogen peroxide. Glutathione is the primary antioxidant, but must be in the reduced state. NADPH is required to keep glutathione in reduced state. Without NADPH (i.e. if G6PD activity is reduced), RBCs will be sensitized to oxidative stresscaused by infection, oxidative drugs, oxidants in food, etc.→ hemolytic anemia
*mutation that causes unstable G6PD is more common in African Americans
toxic metabolites of oxygen
- reactive oxygen species (super oxide, hydrogen peroxide, hydroxyl radical)
- nitric oxide and derivatives
- hypochlorous acid (activated phagocytes)
