Metabolism Of Fructose And Galactose Flashcards
Describe fructose metabolism
• Dietary sources of fructose
– Sucrose – Digested by sucrase
– Fruits and honey
– High fructose corn syrup (55% fructose/ 45% glucose) – Sorbitol (forms fructose by sorbitol dehydrogenase)
- Absorbed by GLUT-5 (facilitated diffusion)
- Liver
- Fructokinase
- Aldolase B in liver (Same aldolase B of glycolysis)
- Higher affinity for Fructose 1,6 bisphosphate (glycolysis) than for Fructose 1- phosphate (fructose metabolism)
What is high fructose corn syrup?
- Sweetener in beverages, ….
- Higher incidence of obesity
- Limit dietary HFCS content
- Processed foods and beverages
What is the purpose of aldolase B?
Aldolase B: Higher affinity for Fructose 1,6-bisP (glycolysis) than for Fructose 1-P (fructose metabolism)
What is benign fructosuria( essential fructosuria)?
- Liver fructokinase deficiency
- Fructose NOT metabolized and excreted in urine
- No toxic metabolites accumulate – Asymptomatic
- Urinalysis shows reducing sugar, that is NOT glucose or galactose
- Detected by abnormal urinalysis report
What is hereditary fructose interppolerance?
- Liver Aldolase B deficiency
- Dietary sucrose/fructose→Fructose1-phosphate accumulates
• Trapping of Pi
– results in ATP deficiency→ inhibits gluconeogenesis
– Inhibits glycogenolysis
- Leads to hypoglycemia (drowsy and apathetic)
- Remember, hypoglycemia following sucrose or fructose (trigger)
- After weaning and fruits added (6-8 months of life
What is the significance of hereditary fructose intolerance?
- Continued dietary fructose/ sucrose/ sorbitol → hepatocellular failure and jaundice
- Urinalysis shows reducing sugar (fructose) that is NOT glucose
- Children with fructose intolerance do NOT have cataracts (Remember!!)
- Avoid dietary fructose→ good dental health and NO dental caries!!
- Have aversion to sweets!!
• Diagnosis: Hypoglycemia following sucrose/ fructose in diet,
reducing sugar in urine and enzyme assays
Describe the synthesis of fructose from glucose (polyol pathway
- Fructosecanbesynthesizedfromsorbitol (Children with fructose intolerance avoid sorbitol)
- Sorbitol (sugar alcohol) from glucose by aldose reductase
- Aldosereductaserichinlens,retina,peripheral nerves and seminal vesicles
- Polyol pathway forms fructose in seminal vesicle – rich in sorbitol dehydrogenase (fructose: Main fuel for spermatozoa)
Describe the significance of the polyol pathway 9f the in uncontrolled diabetes mellitus
In uncontrolled diabetes mellitus,
• Plasma glucose, enters lens and forms sorbitol by aldose reductase
- Sorbitol (osmotically active) increases water content of lens, results in cataract (decreased lens transparency)
- Sorbitolispartlyimplicatedinpathogenesisof microvascular complications of diabetes mellitus (neuropathy, nephropathy, retinopathy) – Insulin independent glucose uptake
Describe the significance of polyol pathway in galactosemia
• In galactosemia,
– Elevated blood galactose →entry of galactose into lens
– Galactose → galactitol by aldose reductase
– Galactitol (osmotically active) increases water content of lens → cataract (Lens opacity)
– Infants with untreated galactosemia have cataracts
Describe the galactosemia as a case report
• A 3-week-old infant has worsening jaundice
• Vomiting after feeds and failure to thrive
• Liver enlarged (hepatomegaly)
• Early cataract formation
• Developmental milestone delay
• Classical triad: liver damage, developmental
delay and cataracts
• Urine positive for reducing sugar (not glucose)
• Inborn error of galactose metabolism???
Summarize galactosemia metabolism
• Lactose (milk sugar) (β1→4 linkage)
– Intestinal lactase to glucose and galactose
- SGLT-1 (Sodium dependent glucose transporter-1)
- Liver
• Galactokinase, galactose 1-phosphate uridyl transferase (GALT)
and epimerase
• Galactose eventually converted to glucose (glycogen)
What is classical galactosemia?
- Galactose 1-phosphate uridyl transferase deficiency (GALT)
- Autosomal recessive
- Galactose and galactose 1-phosphate accumulate
- Presentation: 2nd -3rd week of life
• Galactose 1-phosphate → trapping of Pi → decreased gluconeogenesis and glycogenolysis →Hypoglycemia
• Remember, hypoglycemia after dietary lactose (milk) or galactose (trigger!!!)
• Galactose 1-phosphate and galactitol accumulation→ Jaundice
and hepatomegaly
Explain the effects of galactosemia
- Lens: Galactose → galactitol (aldose reductase)
- Galactitol increases lens water content→ cataracts
• Galactose 1-phosphate and galactitol accumulate in brain cause
neurological damage, learning disability and milestone delay
• Newborns screening: Heel prick test
– Measure Galactose or galactose 1-phosphate or GALT activity
• Urinalysis: Reducing sugar (galactose) that is NOT glucose
Explain the management of galactosemia
• Dietary exclusion of galactose/ lactose
– Improves liver function and cataracts
– Effect on learning disability limited and varied
- Breast feeding stopped
- Substitute soy-milk or lactose-free milk (not Lactaid)
- Lead near normal lives, except lifelong dietary restrictions
- Monitor Galactose 1-phosphate levels
• Females with treated galactosemia, have delayed puberty and
premature ovarian failur
Describe non-classical galactosemia
- Galactokinase deficiency
- Lens Galactitol formation → Cataracts
- NO galactose 1-phosphate accumulation
- Less severe than classical galactosemia
- Urine positive for reducing sugar (galactose)
- Monitor Galactitol levels
• Dietary lactose/ galactose restriction
