Biochemistry-Fructose and Galactose Metabolism Flashcards
What enzyme is the primary phosphorylator of fructose? Why isn’t hexokinase in the picture?
Fructokinase to make fructose-1-P. Hexokinase is normally saturated with glucose and has a low affinity for fructose. Hexokinase will only phosphorylate fructose to fructose-6-P if cellular concentrations become unusually high.
How does metabolism of fructose-1-P differ from fructose-1,6-BP in glycolysis?
Aldolases A,B and C can all work on fructose-1,6-BP to make DHAP and glyceraldehyde-3-P. Aldolase B only works on fructose-1-P to make DHAP (which can enter glycolysis) and glyceraldehyde.
What is our main dietary source of fructose?
Sucrose. It is a disaccharide composed of fructose and glucose
A patient has fructose in their urine. What enzyme is deficient in this typically benign condition?
This patient has fructosuria. It is a condition where fructose cannot be metabolized because there is a genetic mutation in fructokinase and fructose cannot be metabolized.
A mother brings her baby girl in after weening her off of milk complaining of vomiting and jaundice. What would you test for and how might fructose be causing these symptoms?
Test for fructose in the urine to confirm suspicions of hereditary fructose intolerance. She may have a mutation in aldolase B that results in accumulation of fructose-1-P and thus a drop in inorganic Pi…and thus a drop in ATP. Sucrose, sorbitol and fructose must be removed from the diet.
Where are some of the places glyceraldehyde can go after it is formed in fructose metabolism?
Synthesis of phosphoglycerides and triacylglycerols. It can also be made into DHAP and glyceraldehyde-3-P and sent through glycolysis.
Why is fructose metabolism faster than glucose metabolism?
The pathway bypasses phosphofructokinase-1
Where does most intracellular mannose come from?
Fructose. It is 1st phosphorylated by hexokinase to form fructose-6-P. Phosphomannose isomerase then converts it to mannose-6-P.
How do sperm “pack their lunch” before going on their journey?
The polyol pathway. They use fructose as their energy source and often our body must synthesize fructose from glucose via sorbitol intermediate and the enzymes aldose reductase and sorbitol dehydrogenase.
How is sorbitol made in the lens, nerves and kidneys?
Aldose reductase reduces glucose to sorbitol.
Why do diabetics often experience peripheral neuropathy, cataracts, and microvascular problems leading to retinopathy and nephropathy?
Entry of glucose into the lens, retina, nerves and kidney is not controlled by insulin. Thus, hyperglycemic conditions causes mass entry of glucose into the cells of these organs where it is reduced by aldose reductase to sorbitol and trapped. Sorbitol cannot be converted to fructose because sorbitol dehydrogenase is absent in these organs. Accumulation of sorbitol makes the cells hyper osmotic, they swell and lead to these pathologies.
How is galactose modified so it can be used in glycolysis?
1st, it is phosphorylated to form galactose-1-P by galactokinase. It then reacts with UDP-glucose and the enzyme GALT to form glucose-1-P and UDP-galactose. UDP-4-hexose-epimerase can then turn UDP-galactose into UDP glucose where it can be used in glycogen and lactose synthesis, glycolysis, glycolipids, glycoproteins and glucosaminoglycans.
How can galactose cause cataracts?
Galactose is not controlled by insulin and can enter the lens freely. At high concentrations of blood galactose, aldose reductase reduces galactose to galactitol. This really only happens when someone is deficient in galactokinase in non-classic galactosemia. Galactitol accumulation makes cells hyper osmotic and can destroy the tissue.
A mother brings her baby in complaining of vomiting, jaundice and diarrhea. Your findings indicate the baby will be at risk for liver, kidney, nerve and eye damage if she continues to ingest galactose. What enzyme is commonly absent in these kinds of cases?
GALT (galactose-1-P uridylyltransferase), resulting in classic galactosemia. Galactitol and galactose-1-P accumulate in mainly the liver, but also in the lens, nerves and kidneys and can result in severe mental retardation if diet is not adjusted.
What enzyme is deficient in people who are lactose intolerant? How do they still get UDP-galactose to tissue if they cannot ingest lactose?
beta-galactosidase. UDP-hexose-4-epimerase can convert UDP-glucose to UDP-galactose efficiently.
How do the cells in a mother’s mammary glands synthesize lactose that will be secreted in breast milk?
Protein A (beta-galactosyltransferase) and Protein B (alpha-lactalbumin) come together to form lactose synthase (UDP-galactose:glucose galactosyltransferase). Lactose synthase transfers UDP-galactose to glucose, releasing UDP and forming lactose.
How does glyceraldehyde created by aldolase B enter glycolysis?
Triose kinase phosphorylates it to form glyceraldehyde-3-P and it enters after they glycolytic control point PFK-1.
Why can we get by not ingesting galactose?
It can be synthesized from glucose-1-P after it is converted to UDP-glucose via the enzyme UDP-glucose pyrophosphorylase. UDP-glucose then epimerizes via epimerase into UDP-galactose
How does glycerol get into glycolysis?
Glycerol is phosphorylated by glycerol kinase to form glycerol-3-P. Glycerol-3-P is then oxidized by glycerol dehydrogenase to form DHAP and NADH.
