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Lecture notes of 6 pages for the course Metabolic Pathways at QMUL
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Pentose phosphate pathwaysLearning objectives:
1. Identify the following in the pentose phosphate pathway:
- Irreversible steps
- Committed steps
- Rate limited steps
- Products
2. Describe the oxidation & carbon reducing stages of the pentose phosphate pathway.
THE SUGAR RIBOSE IS PART OF THE PENTOSE PHOSPHATE PATHWAY
LO1. IDENTIFY THE FOLLOWING IN THE PENTOSE PHOSPHATE PATHWAY
LO2.DESCRIBE OXIDATION & CARBON RECYCLING STAGES OF PENTOSE PHOSPHATE PATHWAY
The pentose phosphate pathway
Also called phosphogluconate pathway or hexose monophosphate shunt (pushing or driving force)
Purpose: produce metabolites for cellular biosynthesis
- NADPH: reductant (reducing agent) in biosynthesis of
fatty acids
Cholesterol
Nucleotide
Neurotransmitter synthesis
Detoxification (reduction of oxidised glutathione and cytochrome P450 monoxygenases)
- Ribose 5-phosphate
Precursor in nucleotide biosynthesis of RNA and DNA, NAD(P) + and CoASH
Not required for energy production
Major tissues:
- Liver
- Adipose (fat)
- Adrenal cortex
- Mammary glands
- Gonads
How does it work?
- The reaction can be divided into 2 phases
- Phase 1: Oxidation and decarboxylation (of the 6-C sugar glucose-6-P)
2 moles NADPH
Ribose-5-phosphate (5-C sugar)
- Phase 2: recycling
Dispersal of excess C-5 carbon units
Glycolytic intermediates eventually produced
Phase 1: oxidation and decarboxylation
Glucose-6-phosphate dehydrogenase catalyses oxidation of the aldehyde (hemiacetal) at C1 of G6P to a carboxylic acid
in ester linkage
NADP+: electron acceptor
G6P is shunted from glycolysis
, 6-phosphogluconolactonase catalyses hydrolysis of the ester linkage resulting in ring opening
The product is 6-phosphogluconate
Although ring opening occurs in the absence of a catalyst, the lactonase speeds up the reaction decreasing the lifetime
of the highly reactive and thus potentially toxic 6-phosphogluconolactone
Phosphogluconate dehydrogenase catalyse oxidative decarboxylation of 6-phosphogluconate to yield the 5-C ketose
ribulose-5- phosphate
The OH at C3 (C2 product) is oxidised to a ketone
This promotes loss of the carboxyl at C1 as CO2
NADP+ : Oxidant
NADPH and NADP+
Reduction of NADP+ (as with NAD+) involves transfer of 2 electrons and 1 H+ to the nicotinamide moiety
NADPH functions as donating electrons
NADPH, a product of the pentose phosphate pathway functions as a reductant in anabolic pathways
- E.g. fatty acid synthesis
NAD+ serves as an electron transporter in catabolic pathways, in which metabolites are oxidised
The resultant NADPH is reoxidised by the respiratory chain, producing ATP
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