Pentose Phosphate
CH339K
Pentose Phosphate
An example of a pathway that can be both:
• Anabolic
–
–
•
Generates ribose-5-phosphate for nucleotide
synthesis
Metabolizes dietary pentoses into
glycolytic/gluconeogenic intermediates.
Catabolic
–
–
–
Generates reducing power (NADPH)
Can completely oxidize glucose
Can carry on into glycolysis
Aka Hexose Monophosphate Shunt
NADH vs NADPH
As a general rule of thumb:
• NAD+/NADH is used in catabolic processes
• NADP+/NADPH is used in anabolic processes
G3P to
Glycolysis
Oxidative Phase
1) Lose a carbon
2) Reduce 2 NADP+
lactonase
H2O
Better Picture
1)
CH2OPO3-2
CH2OPO3-2
O H
H
O
Glucose-6-Phosphate dehy drogenaseH
H
OH
H
H
HO
OH
H
+
NADP
OH
+
OH
H
OH
O
O
H
H
O
6-Phosphpgluconolactone
CH2OPO3-2
H
H
HO
NADPH, H
Glucose-6-phosphate
2)
OH
6-Phosphogluconolactonase
C
OH
HC OH
HO CH
O
HC OH
HO
H
OH
H
H2O
+
HC OH
CH2OPO3-2
6-Phosphpgluconolactone
6-Phosphogluconate
3)
O
OH
C
HC OH
H2C OH
Phosphogluconate Dehy drogenase
HO CH
HC OH
HC OH
HC OH
C O
+
CO2
HC OH
+
NADP
+
NADPH, H
CH2OPO 3-2
CH2OPO3-2
6-Phosphogluconate
Ribulose-5-phosphate
Glutathione
-SH containing tripeptide
Glu-Cys-Gly
Amino of Cysteine linked to g-carboxyl of glutamate
Commonly used for reducing agent in cells
Oxidizes to for disulfide-linked GSSG
Rereduced to GSH using NADPH
2
GSH
NADP+
Glutathione
Reductase
NADPH + H+
GSSG
Making Glutathione
•
For the Reaction to form GSH:
GSSG + 2e- + 2H+
⇄
2GSH
-0.23 V
NADPH + H+
⇄
NADP+ + 2e- + 2 H+
+0.32 V
GSSG + NADPH + H+
⇄
2GSH + NADP+
+0.09 V
We can figure out DGo from what we learned about
redox reactions
ΔG o' = -nFΔE o'
ΔG o' = -2(96480 JV -1mol-1 )(0.09 V)
ΔG o' = -17.37 kJmol-1
For what it’s worth…
Divicine is found in fava beans and
some other legumes
Favas (broad beans) are common
foodstuffs in the old world.
Largest production in Europe and
China.
The parent plant, Vicia faba, is
among the oldest cultivated plants ~6,000 years.
Glucose-6-P Dehydrogenase
Deficiency
•
•
•
•
•
•
Effects ~ 4*108 people worldwide
Most common human genetic disease
Lack of G-6PD means lack of NADPH
Lack of NADPH means lack of GSH
Lack of GSH means excess of peroxides
RBC membranes particularly susceptible to
peroxides
• Hemolytic Anemia
Harmful Agents for G6PDD Sufferers
Antimalarials
Analgesics
Antibiotics
Anthelmintics
Miscellaneous
Primaquine
Pamaquine
Chloroquine
Aspirin
Bufferin
Anacin
Excedrin
Empirin
APC Tablets
Darvon Compound
Coricidin
Sulfanilamide
Sulfapyridine
Sulfadimidine
Sulfacetamide
Glucosulfone
sodium
Nitrofurantoin
Furazolidone
Nitrofurazone
Dapsone
Sulfoxone
Sulfisoxazole
B-Naphthol
Stibophen
Niridazole
Probenecid
Thiazide Diuretics
Phenothiazine
Chloramphenicol
Orinase
Dimercaprol
Methylene blue
Naphthalene (moth
balls)
Vitamin K
Fava beans
G3P to
Glycolysis
H2C OH
Non-oxidative phase
C O
HC OH
HC OH
CH2OPO 3-2
Ribulose-5-phosphate
Isomerase
Epimerase
H2C OH
HC O
C O
+
HO CH
HC OH
HC OH
HC OH
HC OH
CH2OPO 3-2
Xy lulose-5-Phosphate
CH2OPO 3-2
Ribose-5-Phosphate
Transketolase
H2C OH
C
O
HO CH
O
CH
HC OH
HC OH
HC OH
HC OH
CH2OPO 3-2
Gly ceraldehy de-3-Phosphate
CH2OPO 3-2
Sedoheptulose-7-Phosphate
Transaldolase
HC OH
HC OH
HC OH
CH2OPO 3-2
Ery throse-4-Phosphate
HC OH
CH2OPO 3-2
Gly ceraldehy de-3-Phosphate
C
O
HC OH
HC OH
Fructose-6-Phosphate
H2C OH
CH
C
HO CH
CH2OPO 3-2
Transketolase
O
H2C OH
O
HO CH
HC OH
HC OH
CH3
Fructose-6-Phosphate
Transketolase moves 2-carbon units
Transaldolase moves 3-carbon units
Lack of transketolase can cause hepatosplenomegaly and liver cirrhosis
in childhood.
Verhoeven, N. M. et al (2001) Transaldolase Deficiency: Liver Cirrhosis Associated with a New Inborn
Error in the Pentose Phosphate Pathway , Amer. J. Hum. Gen. 68(5): 1086-1092.
Control
• Conversion of glucose-6-Pi to the lactone is
essentially irreversible.
• The enzyme, glucose-6-phosphate
dehydrogenase, controls the rate of the
pathway.
– NADPH competes with NADP for binding in he
active site;
– ATP competes with glucose-6-phosphate.
• At high [NADPH] and/or high [ATP], entrance
into the pathway is restricted.
Products in the pathway can be withdrawn at
several points