Key Concepts: The Pentose Phosphate Pathway
The pentose phosphate pathway takes place within the cytoplasm
Aka hexose monophosphate shunt or phosphogluconate pathway
Reduces two molecules of NADP to NADPH (nicotinamide adenine
dinucleotide phosphate) for each glucose-6-phosphate that is oxidatively
decarboxylated to ribulose-5-phosphate.
NADPH is functionally similar to NAD however, NADPH is the primary
reductant in the cell, whereas, NAD is the primary oxidant.
The PPP is also responsible for producing ribose-5-phosphate which provides
the ribose sugar backbone that anchors the nucleotide base to DNA and RNA
Pentose Phosphate Pathway is critical for the cell
There are two main phases for PPP:
o The oxidative phase generates NADPH which is required for many
biosynthetic pathways and for detoxification of reactive oxygen species
o The non-oxidative phase interconverts 3C, 4C, 5C, 6C and 7C
monosaccharides to produce ribose-5-phosphate for nucleotide
synthesis, and also to regenerate glucose-6-phosphate to maintain
NADPH production by the oxidative phase.
o Glucose-6-Phosphate Dehydrogenase (G6PD) - This is the first
commited step in the pathway and is feedback-inhibited by NADPH.
o Transketolase and Transaldolase - (converts ketose to aldose and
aldose to ketose), together these two enzymes catalyze the reversible
"carbon shuffle" reactions of the nonoxidative phase of the pathway
Pathways requiring NADPH include:
Fatty acid biosynthesis
Reduction of oxidized glutathione (critical in RBC production)
Cytochrome P450 monooxygenases
Tissues with active PPPs.
o Adrenal gland - steroid synthesis
o Liver - fatty acid and cholesterol synthesis
o Testes and Ovaries - steroid synthesis
o Adipose tissue and Mammary gland - fatty acid synthesis
o Red blood cells - maintenance of reduced glutathione
Regulation of Pentose Phosphate Pathway
Glucose 6 Phosphate dehydrogenase is rate limiting
4 different metabolic scenarios govern how glycolysis and the pentose
phosphate pathway are intertwined
1. Scenario where you need R5P in which you have a lot