Fructose and Galactose B&B Flashcards
how are galactose vs fructose taken up by the body? (Transporters)
galactose: via SGLT1 (Na+ dependent)
fructose: via GLUT-5 (facilitated diffusion)
both leave enterocytes via GLUT-2
what 2 enzymes are required to funnel fructose into glycolysis?
fructose found in sucrose (glucose + fructose)
- fructokinase (liver)
- aldolase B
note fructose is metabolized much faster than glucose because it enters pathway after PFK1 (rate limiting enzyme)
how do essential fructosuria and hereditary fructose intolerance differ in their presentation?
essential fructosuria: deficiency of fructokinase (liver) —> benign, fructose not taken up by liver cells and appears in urine
hereditary fructose intolerance: deficiency of aldolase B —> fructose-1-phosphate accumulations, ATP depletes —> decreased gluconeogenesis / glycogen breakdown —> liver failure
what causes hereditary fructose intolerance and how does it present? (2)
deficiency of aldolase B —> fructose-1-phosphate accumulates (recall aldolase b converts this into glycolysis substrates) —> ATP depletes
- decreased gluconeogenesis —> hypoglycemia, vomiting
- decreased glycogen breakdown —> hepatomegaly, liver failure
(also hyperuricemia from AMP breakdown)
presents in baby that just weaned from breast milk (once they start getting exposed to fructose), reducing sugars (fructose, galactose) in the urine
Pt is a 6mo F presenting with failure to thrive and seizures that began presenting after she was weaned from breast milk. PE is notable for an enlarged liver. Lab findings include hypoglycemia. What could be going on?
Hereditary Fructose Intolerance: aldolase B deficiency —> depletion of ATP —> decreased gluconeogenesis (hypoglycemia, vomiting, seizures) and decreased glycogen breakdown (hepatomegaly, liver failure)
presents in babies just weaned from breast milk - when they begin to get exposed to fructose (recall sucrose = glucose + fructose)
what is the function of the Polyol Pathway?
alternative glucose metabolism, converts glucose to sorbitol (via aldose reductase) then into fructose
- note that in diabetes, sorbitol builds up because of Polyol Pathway
- also note patients with Hereditary Fructose Intolerance must avoid sorbitol because of Polyol Pathway
into what metabolic pathways can galactose be funneled via its metabolism (2)?
galactose - found in lactose (glucose + galactose)
- glucose-1-phosphate —> glycogen synthesis (via GALT - galactose 1-phosphate uridyltransferase)
- glucose-6-phosphate —> glycolysis
what causes Classic Galactosemia and how does it present?
AR deficiency in GALT (galactose 1-phosphate uridyltransferase), which converts galactose-1-phosphate into glucose-1-phosphate (—> glycogen synthesis or glycolysis)
galactose-1-phosphate accumulates, depleting ATP (phosphates are unavailable)
presents in first few days of life - vomiting/diarrhea following milk consumption
galactose/galactitol (via Polyol Pathway) accumulate —> liver failure, jaundice, hepatomegaly, failure to thrive, cataracts (if untreated), severe intellectual disability
Pt is a newborn presenting with jaundice, hepatomegaly, and failure to thrive in the first few days of life. Vomiting and diarrhea was noted to develop following first consumption of milk.
What is the diagnosis?
Classic Galactosemia: AR deficiency in GALT (galactose 1-phosphate uridyltransferase), which converts galactose-1-phosphate into glucose-1-phosphate (—> glycogen synthesis or glycolysis)
presents in infancy (following milk consumption)
galactose/galactitol (via Polyol Pathway) accumulates, ATP depleted (due to phosphate transfer) —> liver failure, jaundice, hepatomegaly, failure to thrive, cataracts (if untreated), severe intellectual disability
how does galactokinase (GALK) deficiency present?
galactokinase (GALK) converts galactose —> galactose-1-phosphate (which can then be converted via GALT to enter glycogen synthesis or glycolysis)
galactose accumulates in blood and urine, cataracts develop in child/young adult
Pt is an 11yo presenting to their eye doctor for vision problems. Cataracts are noted. Labs are taken which note galactose in the blood and urine. What is the diagnosis?
Galactokinase deficiency: converts galactose —> galactose-1-phosphate (which can then be converted via GALT to enter glycogen synthesis or glycolysis)
galactose accumulates in blood and urine, cataracts develop in child/young adult
how does galactokinase deficiency vs classic galactosemia present?
galactokinase deficiency: galactose accumulates in blood/urine, cataracts in child/young adult
classic galactosemia: GALT deficiency —> galactose/galactitol accumulates, jaundice, hepatomegaly, failure to thrive in first few days of life, cataracts if untreated
what is the purpose of a clinitest?
clinitest: colorimetric test that detects reducing sugars in the urine (sugars with free aldehyde or ketone groups, which can be oxidized to carboxylic acid)
ex - glucose, fructose, galactose (NOT sucrose)
positive test indicates pathology - sugars are not normally present in the urine
a patient has a negative urine dipstick test but a positive clinitest - what does this suggest?
dipstick only tests for glucose, clinitest tests for any reducing sugars
therefore, there is sugar in the urine that is not glucose (ex - fructose, galactose)
what 2 glycolysis intermediates can fructose be metabolized into, and what is the significance of this?
fructose —> fructose 1-phosphate (via fructokinase) —> —>
- DHAP (dihydroxyacetone phosphate) - which can be converted to glyceraldehyde-3-phosphate
- glyceraldehyde 3-phosphate
these intermediates are downstream from rate-limiting PFK-1 step —> fructose is metabolized very quickly
