Pentose Phosphate Pathway
Metabolic pathway of carbohydrates that oxidizes glucose-6-phosphate to generate NADPH and provide ribose-5-phosphate for nucleotide synthesis.
Pentose Phosphate has two phases
Oxidative and Non-oxidative
Oxidative phase of Pentose Pathway
is irreversible and highly regulated at the level of glucose-6-phosphate dehydrogenase.
Nonoxidative phase of Pentose Phosphate Pathway
is reversible and flux through this part depends on the needs of the cell for NADPH (for reductive biosynthesis) and ribose for DNA replication
Glucose-6-Phosphate Dehydrogenase
1st and Rate limiting step of pentose phosphate pathway. The irreversible step: (glucose 6 phosphate + NADP >>> 6 phosphoglucanolactone + NADPH) Activated by NADP and glucose
Glucose 6 Phosphate Dehydrogenase deficiency
X-linked recessive disorder that results in hemolytic anemia. This is the most common enzymopathy in humans. (AKA Favism)
DNA Replication
Bidirectional and semiconservative process of replicating DNA. The DNA molecule unzips at the "origin of replication" and each parent strand is a template for the new strand. High fidelity process that is not error-free.
6-phosphogluconolactonase
This is the 2nd step of the Pentose Phosphate Pathway irreversibly hydrolyzes 6-phosphogluconolactose to 6-phosphogluconate
6-phosphogluconate dehydrogenase
6 phosphogluconate undergoes irreversible oxidative decarboxylation to ribulose-5-phosphate, releases CO2, and produces 2nd molecule of NADPH (step 3)
Transketolase
Transfers a 2-carbon residue from a ketose to an aldose. This enzyme has a requirement for a thiamine pyrophosphate prosthetic group.
thyamine pyrophosphate prothetic group
Active enzyme derived from thyamine vital to the PDC. This is also a coenzyme for the transketolase enzyme of the pentose phosphate pathway
transaldolase
Transfers a 3-carbon residue from a ketose to an aldose
Pentose Phosphate Pathway occurs in what part of the cell
entirely in the cytoplasm and is connected to glycolysis
In what tissue does the Pentose Phosphate Pathway occur
Liver, kidney, adipose tissue, adrenal cortex, neurons, RBC's, and gonads
THe Pentose Phosphate Pahway is central for the formation of
NADPH
How many ATP are produced in this pathway
There are no ATP produced
Function of the oxidative phase of the pathway
Produces NADPH
Function of the nonoxidative step of the pathway
Isomerization/epimerization phase
Rearrangement phase
3 Oxidative reactions of the pathway
Three reactions that produce Ribulose 5 Phosphate, CO2, and 2 NADPH from glucose 6 phosphate via these enzymes
1-Glucose 6 Phosphate dehydrogenase
2-6 phosphogluconolactonase
3-6-phosphogluconate dehydrogenase\
Which two enzymes in this pathway produce NADPH
Glucose 6-phosphate dehydrogenase STEP 1*
6-phosphogluconate dehydrogenase STEP 3*
Which enzyme is the rate limiting and primary regulation point of the pathway
Glucose 6-phosphate dehydrogenase
Glucose 6-phosphate dehydrogenase inhibited by
NADPH
Glucose 6-phosphate dehydrogenase deficiency
most common enzymopathy (favism causes it as well-consuming fava beans)
RBC is most affected and so it leads to hemolytic anemia
Mutations of this enzyme protects against Malaria
Overall reaction of the oxidative phase
Glucose 6-Phosphate + 2NADP + H20 >>>>Ribulose 5-Phosphate + 2NADPH +2H + CO2
Nonoxidative reactions of the pathway
-These are reversible and controlled by substrate availability
-Ribulose 5 phosphate is converted to Ribose 5 phosphate or Xylulose 5 phosphate
-These rearrangements produce glycolytic intermediates
Ribose 5 Phosphate is used for
RNA and DNA synthesis
Isomerization of Ribulose 5 Phosphate produces
Ribose 5 Phosphate
Epimerization of Ribulose 5 Phosphate produces
Xylulose 5 Phosphate
Cellular NADPH utilization
-Fatty Acid synthesis
-Regeneration of tripeptide GSH (glutathione)
reduced glutathione is good for
-protection from cancer
-protection of RBC from hemolysis
-detoxification
-activation of sulfhyryl enzymes
So low levels of NADPH means
less reduced glutathione which means less protection of RBC and from radicals
Oxidized glutathione is reduced by
NADPH-dependent glutathione reductase
GSH reacts with active
oxygen metabolites (including H2S2)
Cells need: Ribose 5 Phosphate > NADPH
No need for glucose-6-phosphate dehydrogenase step so glucose-6-phosphate will funnel down glycolysis and make ribose-5-phosphate via fructose-6-phosphate and glyceraldehyde-3-phosphate
Cells need: NADPH = ribose-5-phosphate
The oxidative part of the Pentose Phosphate Pathway will occur and Ribulose-5-phosphate will be converted to Ribose-5-phosphate and the pathway will stop here
Cells need: NADPH > Ribose-5-Phosphate
The oxidative step of the Pentose Phosphate pathway will occur and then from Ribose-5-phosphate it will go to glyceraldehyde-3-phosphate and then go backwards in the glycolytic pathway to once again produce glucose-6-phosphate and go through the oxidative
Cells need: NADPH > Ribose-5-Phosphate (and ATP is required)
The oxidative and nonoxidative phases will occur in order to produce both
Isomerase converts Ribulose-5-Phosphate to Ribose-5-Phosphate
Used for RNA and DNA synthesis (cell division)
Epimerase converts Ribulose-5-Phosphate to Xylulose-5-Phosphate
Used to make intermediates of glycolysis (make ATP)