Fructose, Galactose Metabolism - Abali 3/9/16 Flashcards Preview

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Flashcards in Fructose, Galactose Metabolism - Abali 3/9/16 Deck (17):
1

C6H12O6 molecules and relationships with each other

glucose, galactose, fructose, mannose

  • isomers: same chem formula: all are isomers of one another
  • epimers: vary in config around ONE non-carboxyl group C
    • glucose & galactose : C4 epimers
    • glucose & mannose: C2 epimers
  • enantiomers: L- and D- are mirror images
    • biologically active sugars are Ds

2

ring structure of monosaccharides

aldehyde (keto) group reacts with hydroxyl group of the same sugar

  • rings can open and reclose → can get rotation about C with reactive carbonyl group (anomeric C) → distinct alpha and beta configs (anomers)

3

key mono-, di-, polysaccharides

 

why is sucrose special?

monosacchs: glucose, fructose, galactose

disacchs: maltose (glucose+glucose), sucrose (glucose+fructose), lactose (galactose+clucose), trehalose (glucose+glucose)

  • sucrose has both anomeric carbons fixed in a glycosidic bond

polysacchs: glycogen, starch, cellulose

4

polyol pathway for fructose synthesis

present in many tissues (hepatocytes, ovaries, sem vesicles), not well understood in all

  • seminal vesicles: synthesizes fructose for seminal fluid

glucose → sorbitol → fructose

5

DM2 and sorbitol

diabetes: insulin def/resistance. cells that are not regulated by insulin experience glucose accumulation (kidney, lens, retina, etc)

glucose → sorbitol [aldose reductase]

  • doesnt happen under normal conditions; does in DM2

 

sorbitol accumulation in cells that lack sorbitol DH (kidney, lens, retina, Schwann cells)

  • sorbitol is osmotically active → influx of water, cell swelling
  • retinopathy, cataracts, periph neuropathy

6

fructose metabolism

fructose enters int epi cell through GLUT5, leaves through GLUT2

in liver: fructose → F1P [fructokinase]

extrahepatic tissues: fructose → F1P [hexokinase]

 

F16 splits into 3C molecules → DHAP + glyceraldehyde [aldolase B - rate limiting]

glyceraldehyde → glyceraldehyde3P [triose kinase]

 

yields 2 precursors of TAG synthesis!

  • glyceraldehyde → glycerol [glycerol DH] → glycerol3P [glycerol kinase] + FAs → TAGs
  • glyceraldehyde3P →→→ pyruvate → acetyl CoA → FAs + glycerol3P → TAGs

 

 

7

hereditary deficiencies in fructose metabolism

essential benign fructosuria : fructokinase def

hereditary fructose intolerance (HFI) : aldolase B def

8

aldolase B

enzyme catalyzing rate liiting step in fructose metabolism (low affinity for F1P)

fructose 1P → DHAP + glyceraldehyde

 

normally, a fructose-rich meal leads to fructose accumulation in liver while slow degradation turns them into glycolytic intermeds

  • individuals with HFI (aldolase B def) accumulate higher levels of fructose than normal

9

essential fructosuria (benign)

fructokinase deficiency

  • autosomal recessive (1/130k)
  • benign, asymptomatic
  • fructose accumulation in urine

10

hereditary fructose intolerance

aka fructose poisoning

aldolase B deficiency → intracellular trapping of F1P

sx: P on fructose "takes up space" that would be taken up by inorganic P, leading to...

  • severe hypoglycemia, jaundice, hemmorhage, hepatomegaly, hyperuricemia

tx: detection, rapid removal of fructose/sucrose from diet

11

HFI, F16 buildup, consequences of it

aldolase B deficiency → F1P buildup

P on fructose "takes up space" that would be taken up by inorganic P, leading to hypoglycemia 

how?

  • glycogenolysis inhibited by lack of P (glycogen → G1P)
  • gluconeogenesis inhibited by lack of aldolase B (and its comp inhibition by F1P)
  • lactic acidosis sets in

12

galactose metabolism

G1P uridyltransferase: G1P + UTP → UDP-glucose

 

galactose1P uridyltransferase:

galactose1P + UDP-glucose → G1P + UDP-galactose

 

fates of galactose...

  • UDP-galactose → UDP-glucose [epimerase]
  • enter glycolysis (G1P → G6P → glycolysis)
  • be converted to glucose (G1P → G6P → glucose)

13

hereditary deficiencies in galactose metabolism

1. galactokinase def (nonclassical galactosemia)

2. galactose1P uridylyltransferase def (classical galactosemia) aka GALT

14

galactokinase deficiency

galactose builds up

  • in cells with aldose reductase activity (kidneys, retina, lens, nerve tissue, sem vesicles, ovaries): galactose → galactitol
    • galactitol buildup

 

genetics: rare, autosomal recessive

sx:

  • elevation of galactose in blood and urine (galactosemia/uria)
  • galactitol accumulation (if galactose in diet)
    • can cause cataracts

tx: dietary restriction

15

GALT deficiency

galactose1P uridylyltransferase deficiency

classic galactosemia

GALT deficiency → accumulation of galactose1P and galactitol

 

genetics: autosomal recessive (1/30k)

symptoms: galactosemia, galatosuria, vomiting, diarrhea, jaundice

  • accumulation of galactose1P and galactitol in nerve, lens, liver, kidney tissues → severe mental retardation, liver damage, cataracts

diagnosis/tx: prenatal chorionic villus sampling, newborn screening. removal of galactose from diet.

  • still carries risk of devpt delays, premature ovarian failure for females

16

overarching problem with accumulation of fructose1P and galactose1P

 

link to hyperuricemia

sequestration of inorganic phosphate!

due to...

deficiencies in aldolase B (F1P degradation) and GALT (galactose1P degradation)

 

leads ADP → AMP → IMP → uric acid buildup = hyperuricemia

can ALSO develop hyperuricemia via increased reabs via URAT1 (triggered by lactic acidosis, ketoacidosis) 

17

reducing sugars: definition, test

sugars with free aldehyde/ketone groups that can be oxidized to COOH

 

test: if they react with Cu (blue) → Cu2O (red/orange)

  • shouldn't see it in normal urine bc shouldnt see sugar in urine!

 : urine dipstick to see if sugar is glucose (no glucose, but yet reducing sugar? not diabetes)