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

Gastrointestinal System > Fructose, Galactose Metabolism - Abali 3/9/16 > Flashcards

Flashcards in Fructose, Galactose Metabolism - Abali 3/9/16 Deck (17)
Loading flashcards...
1
Q

C6H12O6 molecules and relationships with each other

A

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
Q

ring structure of monosaccharides

A

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
Q

key mono-, di-, polysaccharides

why is sucrose special?

A

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
Q

polyol pathway for fructose synthesis

A

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

  • seminal vesicles: synthesizes fructose for seminal fluid

glucose → sorbitol → fructose

5
Q

DM2 and sorbitol

A

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
Q

fructose metabolism

A

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
Q

hereditary deficiencies in fructose metabolism

A

essential benign fructosuria : fructokinase def

hereditary fructose intolerance (HFI) : aldolase B def

8
Q

aldolase B

A

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
Q

essential fructosuria (benign)

A

fructokinase deficiency

  • autosomal recessive (1/130k)
  • benign, asymptomatic
  • fructose accumulation in urine
10
Q

hereditary fructose intolerance

A

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
Q

HFI, F16 buildup, consequences of it

A

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
Q

galactose metabolism

A

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
Q

hereditary deficiencies in galactose metabolism

A
  1. galactokinase def (nonclassical galactosemia)
  2. galactose1P uridylyltransferase def (classical galactosemia) aka GALT
14
Q

galactokinase deficiency

A

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
Q

GALT deficiency

galactose1P uridylyltransferase deficiency

A

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
Q

overarching problem with accumulation of fructose1P and galactose1P

link to hyperuricemia

A

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
Q

reducing sugars: definition, test

A

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)