pentose phosphate ch339k. pentose phosphate an example of a pathway that can be both: anabolic...
TRANSCRIPT
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 carbon2)Reduce 2 NADP+
lactonase
H2O
O
OH
HH
H
OH
OH
H OH
H
CH2OPO3-2
O
OHH
H
OH
OH
H OH
CH2OPO3-2
Glucose-6-phosphate 6-Phosphpgluconolactone
Glucose-6-Phosphate dehydrogenase
NADP+
NADPH, H+
O
OHH
H
OH
OH
H OH
CH2OPO3-2
6-Phosphpgluconolactone
C
HC
CH
HC
HC
CH2OPO3-2
O OH
OH
OH
OH
OH
6-Phosphogluconate
6-Phosphogluconolactonase
C
HC
CH
HC
HC
CH2OPO3-2
O OH
OH
OH
OH
OH
6-Phosphogluconate
H2C
C
HC
HC
CH2OPO3-2
OH
OH
OH
OPhosphogluconate Dehydrogenase
NADP+
NADPH, H+
Ribulose-5-phosphate
+ CO2
H2O H+
1)
2)
3)
Better Picture
Glutathione
-SH containing tripeptideGlu-Cys-GlyAmino of Cysteine linked to -carboxyl of glutamateCommonly used for reducing agent in cellsOxidizes to for disulfide-linked GSSGRereduced to GSH using NADPH
2
NADPH + H+
NADP+
GSH
GSSG
GlutathioneReductase
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 Go from what we learned about redox reactions
o' o'
o' -1 -1
o' -1
ΔG = -nFΔE
ΔG = -2(96480 JV mol )(0.09 V)
ΔG = -17.37 kJmol
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.
For what it’s worth…
Glucose-6-P Dehydrogenase Deficiency
• Effects ~ 4*108 people worldwide• Most common human genetic disease• X-linked• 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
Glucose-6-Phosphate Dehydrogenase Deficiency
Cappellini, M.D., and Fiorelli, G. (2008) Glucose-6-phosphate dehydrogenase deficiency, Lancet 371: 64-74.
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
C
HC
HC
CH2OPO3-2
OH
OH
OH
O
Ribulose-5-phosphate
H2C
C
CH
HC
CH2OPO3-2
OH
OH
O
OH
HC
HC
HC
HC
CH2OPO3-2
O
OH
OH
OH
Xylulose-5-Phosphate Ribose-5-Phosphate
Epimerase Isomerase
CH
HC
HC
HC
CH2OPO3-2
OH
OH
OH
OH
C O
H2C OH
CH
HC
CH2OPO3-2
OH
O
+
Transketolase
HC
HC
HC
CH2OPO3-2
OH
OH
OH
CHOH
C O
H2C OH
HC
HC
CH2OPO3-2
OH
OH
CH
HC
CH2OPO3-2
OH
O
CHOH
C O
H2C OH
HC
HC
CH3
OH
OH
Sedoheptulose-7-Phosphate
Glyceraldehyde- 3-Phosphate
Erythrose-4-Phosphate
Fructose-6-Phosphate
Glyceraldehyde- 3-Phosphate
Fructose-6-Phosphate
Transketolase
Transaldolase
Non-oxidative phase
phosphopentose isomerase
Ribulose can be used to make ribose•enediol intermediate
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.
1.
2.
Transketolase uses a TPP cofactor
Transaldolase forms a protonated Schiff base
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.
Multiple Functions of Pentose Phosphate Pathway
Products in the pathway can be withdrawn at several points