Transcript Gly - mustafaaltinisik.org.uk

Fructose Metabolism
Fructose can enter glycolysis and gluconeogenesis.
Glucose is a main metabolic fuel in most organisms.
Other sugars convert to glycolytic intermediates.
•Fructose metabolism is faster than glucose in blood.
•Hexokinase can phosphorylate fructose:
Fructose + ATP  Fructose 6-P + ADP
Km for fructose >> Km for glucose, thus important only if [frucose] is high.
Most of fructose metabolized to fructose 1-P by fructokinase.
Fructose + ATP  Fructose 6-P + ADP
•Adolase B cleaves the molecule of fructose into two 3-Carbon
compounds.
dihydroxyaceton-P + glycealdehyde glycogenesis/gluconeogenesis
after dietary fructose consumption
low blood glucose level
17-19
Excess fructose is toxic.
•Accumulation of fructose 1-P causes damage to liver.
fructosekinase > aldolase B in activity
•Metabolism of (fructose by fructokinase) >> (glucokinase for glucose) in
liver
Generated fructose 1-P stimulates pyruvate kinase.
Hypertriglyceridemia

improper substitute of glucose for diabete patient
Disorder of fructose metabolism
•Essential fructosuria: deficiency of fructokinase
•Hereditary fructose intolerance: deficiency of aldolase B
-Accumulation of fructose 1-P:
inhibits aldolase, phosphohexose isomerase and glycogen phosphorylase
stimulates glucokinase
-Tying up Pi in the form of fructose 1-P makes it impossible for liver
mitochondria to generate ATP by oxidative phosphorylation.
fructose + ATP  fructose 1-P + ATP
ADP + Pi + “energy provided by electron transport chain”  ATP
Net: Pi + fructose  fructose 1-P
The ATP levels fall precipitously inside cells.
Cells cannot perform normal work functions.
•Deficiency of fructose 1,6-bisphophatase causes similar effect.
Galactose metabolism
Galactose can enter glycolysis and gluconeogenesis
Phosphorylation of galactose by galactokinase: Galactose 1-P
UDP-galactose is an epimer of UDP-glucose
recycle
reversible: internal sources for other biosynthesis
Galactosemia
Deficiency of galactose 1-P uridyl transferase
Accumulation of galactose (cataract) or galactose 1-P (damage to liver)
Recycle
17-20
Galactose
Galactitol
Polyol pathway
no reaction
17-23
Other pathways
Pentose phosphate pathway
Produces ribose 5-P and NADPH
Oxidative branch: irreversible, high [NADPH]/[NADP+]
NADPH is a stronger reductant than NADH in cells.
Non-oxidative branch: irreversible
3 glucose 6-P + 6 NADP+
2 fructose 6-P + glyceraldehyde 3-P
+ 6 NADPH + 6H + + 3 CO2
Oxidative branch of pentose phosphate pathway
17-21
Non-oxidative branch of pentose phosphate pathway
17-22
Thiamine pyrophosphate
3 glucose 6-P + 6 NADP+
2 fructose 6-P + glyceraldehyde 3-P
+ 6 NADPH + 6H + + 3 CO2
Oxidative branch of pentose P pathway
17-21
Use of oxidative and nonoxidative branches is dependent on nee
d of NADPH and ribose 5-P in cells
1. When cells need ribose 5-P more than NADPH
Generating ribose 5-P from oxidative branch, reverse reaction in
Non-oxidative branch
Used in muscle , where glucose 6-P dehydrogenase level is low and
nucleotides are stored.
2. Need both ribose 5-P and NADPH
Predominantly oxidative branch and phosphate pentose isomerase
reaction.
3. need NADPH more than ribose 5-P
Generating fructose 5-P and glyceraldehyde 3-P by both branches
Changed to glucose 6-P through gluconeogenesis
Thus, theoretically all glucose can be converted to CO2 and NADPH.
Activity of pentose phosphate pathway
•The cell keeps the ratio of [NADPH]/[NADP+] at above 100 to favor
reductive biosynthesis.
In some tissues such as adrenal cortex, lactating mammary gland and
liver, where fatty acid and cholesterol synthesis are rapid, as much as
30% of glucose is metabolized by the pentose phosphate shunt. (weak in
brain and muscle)
•NADPH as an antioxidant: important to tissues exposed to high oxygen
pressure such as the cornea
Oxidative branch produces NADPH, The first step in oxidative branch is
oxidation of glucose 6-P via glucose 6-P dehydrogenase
Deficiency of glucose 6-P causes hemolytic anemia.
•The pentose phosphate pathway supplies the RBC with NADPH to
maintain the reduced state of glutathione.
-Oxidation of glucose 6-P via glucose 6-P dehydrogenase to produce NADPH.
•The inability to maintain reduced glutathione in RBCs leads to increased
accumulation of peroxides, predominantly H2O2, that in turn results in a
weakening of the cell wall and concomitant hemolysis.
•The pentose phosphate pathway in erythrocytes is essentially the only
pathway for these cells to produce NADPH. Any defect in the production
of NADPH could, therefore, have profound effects on erythrocyte survival.
•Oxidant drugs: increase the oxidation of glutathione
Many anti-malarial drugs, etc.
-Plasmodium requires the reducing power of NADPH for their life cycle.
-Favism
-Viral hepatitis, pneumonia, and typhoid fever
a
b
g
Glu
Cys
a
Gly
a
g-Glu
g-Glu


Cys SH + SH  Cys


Gly
Gly
g-Glu

2 Cys SH + H2O2

Gly
Glutathione
peroxidase
g-Glu
g-Glu


Cys S  S  Cys


Gly
Gly
g-Glu
g-Glu


Cys S  S  Cys + 2 H2O


Gly
Gly
g-Glu
g-Glu


Cys S  S  Cys + NADPH + H+


Gly
Gly
Glutathione
reductase
g-Glu

2 Cys SH + NADP+

Gly
Box 17-1,2,3
Fructose is a major sugar in semen
•Advantage over bacteria
•Polyol pathway is present in the seminal vesicles for fructose synthesis
for seminal fluid (energy source for spermatozoa)
Amino sugar synthesis from glucose (표 17-3 참고)
•Essential pentosuria
Synthesis of amino sugars
17-24
essential
pentosuria
Uronic acid pathway
17-25