Metabolism of fructose, galactose & lactose Flashcards
How can fructose be derived? How is fructose uptake done? How does hexokinase ‘act’ which fructose? Where is it found?
- Fructose contributes 10% of calories in the Western diet
- Fructose mainly derived from sucrose in diet
- Fructose also derived from fruits, honey, high-fructose corn syrup (sweetener in soft drinks and other foods)
- Fructose uptake by cells- insulin-independent
- Fructose does not promote insulin secretion
- Hexokinase has low affinity (high Km) for fructose, does not phosphorylate it at normal cellular concentrations
- Fructokinase, found in liver, kidney & intestinal mucosa phosphorylates fructose
How can fructose enter glycolysis, gluconeogenesis, triacylglycerol synthesis and phospholipid synthesis?
How is the rate of fructose metabolism in comparison to glucose and why? How else is fructose different from glucose? What does it do in terms of fat production and tag levels?
•The rate of fructose metabolism is faster than that of Glucose.( why? )
-Reason: Trioses formed from Fructose -1-PO4 bypass the main regulatory enzyme of glycolysis (PFK-1)
•Thus Fructose can be cleared off from plasma earlier than glucose.
•The rapid entry of fructose into glycolysis leads to increased rate fatty acid synthesis in the liver & thereby promotes fat production.
•Plasma triacylglycerol (TAG) levels are increased by the ingestion of large amounts of either fructose or sucrose
•There is a correlation between sugar (Sucrose or fructose) consumption, high plasma lipid levels and atherosclerosis.
Explain the polyol pathway! Where is aldose reductase found? What uses fructose as its major carbohydrate energy source? Where is sorbitol dehydrogenase found? What happens to sorbitol in the liver?
Aldose reductase is found in retina, lens, Schwann cells of peripheral nerves, liver, kidney, RBCs, ovaries, seminal vesicles
•Sperm cells use fructose as major carbohydrate energy source
•In liver, any available sorbitol is converted to fructose through this pathway, so it can enter glycolysis
Sorbitol dehydrogenase is found in liver, ovaries & seminal vesicles.
What happened in hyperglycemic conditions( diabetes mellitus) ? What are the signs seen in a ppt with diabetes mellitus?
In hyperglycemic conditions (diabetes mellitus)
- Large amounts of glucose enters cells that do not need insulin for glucose uptake
- High levels of glucose & NADPH, lead to high level of sorbitol
- In retina, lens, nerves & kidney sorbitol D.H. absent
- Causes accumulation of sorbitol in these cells
- Sorbitol is osmotically active, causes cell swelling
- Sorbitol accumulation in uncontrolled diabetes
- can lead to Cataract in lens, peripheral neuropathy, nephropathy, retinopathy
What are the disorders of fructose metabolism? (2) How do they differ? Which enzymes are absent in each? What are the symptoms seen
1.Essential fructosuria
•Autosomal recessive
•Lack of fructokinase
•Benign condition
•Fructose excreted in urine
2. Hereditary fructose intolerance
- Autosomal recessive
- Absence of aldolase B
- Symptoms appear when baby is fed food containing sucrose or fructose
- Fructose trapped as fructose 1-phosphate (sequestering of phosphate)
- Decreased Pi and ATP, increased AMP level
•In Hereditary fructose intolerance when there is a low level of ATP, what can it lead to ? When there is a high level of AMP what can it lead to?
How is galactose acquired? Where does the metabolism of galactose happen? Is Galactose entry insulin dependent? What is the importance of galactose? What is used as a carrier of Galactose?
- In diet galactose is obtained from the digestion of lactose (by the action of lactase)
- Lysosomal degradation of glycoproteins & glycolipids releases galactose
- Galactose undergoes metabolism in liver and brain
- Galactose entry into cells is not insulin dependent
Importance of Galactose:
- Galactose is required for the synthesis of compounds such as;
- Lactose (in females during lactation)
- Keratan sulfate (an example for GAG)
- Glycoproteins
- Glycolipids
- UDP acts as carrier of Galactose during the synthesis of above compounds
Draw how galactose is used to synthesize lactose, glycolipids, glycoproteins, glycoaminoglycans
•Classic galactosemia: What causes this deficiency? What are the symptoms? What does accumulation of galactose 1-phosphate cause? What is the treatment?
- Deficiency of galactose 1-phosphate uridyl transferase
- Within a few days after first intake of milk- vomiting, diarrhea, irritability, poor feeding, convulsions, jaundice
- Galactosemia ( galactose in blood) and galactosuria (galactose in urine)
What does Galactokinase deficiency causes? Which one is less sever from Galactokinase deficiency:and classic galactosemia?
Treatment removal of galactose from the diet.
At risk for developmental delays despite adequate treatment, premature ovarian failure in females
Galactokinase deficiency:
- Causes galactosemia & galactosuria
- Galactitol accumulation in lens, cataracts seen
- Less severe than classic galactosemia
What is lactose? How is it made? What is the dietary source? Where is the site of lactose synthesis? What is the main enzyme? Name the components of the main enzyme
It is a disaccharide – Galactose + Glucose(β 1->4)
Lactose is synthesized in lactating mammary gland
Dietary source: Milk, dairy products
Site of lactose synthesis: Golgi
** Main enzyme: Lactose synthase-** transfers galactose from UDP-galactose to glucose
Lactose synthase – composed of 2 proteins
- "A" protein = **ß D-galactosyltransferase** (GT, in most tissues)
- "B" protein = **α-lactalbumin** (α-LA, found only in mammary glands
What happens during the synthesis of glycoprotein?
Lactose synthase is the one that converts UDP-D-galactose + D-glucose to lactose + UPD
Give the summary of lactose
Glalactose in the diet is not required to make lactose . Glucose can its self become UDP Galactose and combine with glucose to from lactose. So lactose and galactose are not essential nutrients
Compare Lactose intolerance and galactosemia ? Both conditions lactose ingestion should be avoided. Lactose intolerance is a problem in the intestine. Galactosemia is a metabolic problem ( more serious)
