Week 4 - Pentose Phosphate Pathway Flashcards
Pentos phosphate pathway
What are purposes?
Uses glucose to produce NADPH and 5 carbon sugars
*Occurs in ALL cells, regardless of mitochondria
The reducing power of NADPH is used for:
- fatty acid synthesis
- cholesterol synthesis
- nucleotide synthesis
- oxidation of toxins by cytochrome P450 enzymes
- generation of reduced glutathione
The 5 carbon sugars are used for synthesizing nucleotides (DNA, RNA synthesis)
What are the two phases?
Oxidateive phase
first two rxns, NON reversible, where NADPH is generated
converts glucose to ribulose 5 phosphate molecule
and regenerative phase
converts ribulose 5 phosphate to molecules with 3 or 6 carbons… used in glycolitic pathways..
The second phase is reversible
the key enzymes are transketolase and transaldolase; their reactions are reversible
xylulose 5-phosphate is a key metabolic regulator
Overview of pathway
What are the main enzymes?
transketolase and transaldolase (reversable reactions)
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First reaction.. G6P dehydrogenase**
converting an alcohol into a carboxylic acid…
Know the enzyme, glucose 6 phosphate deficiency.
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Glutathione
Glutathione is a tripeptide: glutamic acid, cysteine and glycine.
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The bond between glutamic acid and cysteine is not a typical peptide bond though– glutamic acid’s side chain is linked to cysteine’s amine.
Glutathione’s role is to neutralize free radicals so that they do not damage the cell.
Glutathione
Oxidized or reduced..
reduced form, monomers, molecules are free… S has electrons on it
Oxidized form, remove electrons on sulfers to created a bond.
These two forms are in equilibrium.
The oxidize form can take electorns (not a good antioxidant) but the reduced form is.
What is the reducing power of NADP used for in terms of glutathione?
The reducing power of NADP is used to maintain glutathione in a reduced state, so that it can remove hydrogen peroxide from the cell.
glutathione is used to remove h2O2 out of cell to generate wtaer.. main round of antioxidant defence in cells…
Glutathione peroxidase can take care of free H2O2, if the peroxidase isnt working you can get hydroxy radical which is bad.
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favism - glucose 6 phosphate dehydrogenase deficiency - another name for it.
derived from fava beans.. sulfa antibiotics… mediteranian descent
Why? because ppl who eat fava beans get a chemical from them that generates a lot of H2O2..
pts get a hemolytic anemia response* bad.
THis is on all USLME practice exams…
Glucose 6 Phosphate dehydrogenase deficiency
G-6-PDH deficiency is a common inborn error of metabolism. It is an X-linked recessive trait.
Their glucose 6-phosphate dehydrogenase is not completely inactive. It can provide enough flux through the pentose phosphate oxidative phase to provide reducing power for glutathione. Under normal conditions, there is not abnormally high oxidative stress.
Affected people are asymptomatic. . . until they are not
If people with glucose 6-phosphate dehydrogenase deficency are exposed to xenobiotics which are detoxified by NAPDH consuming enzymes, their capacity to regenerate NAPDH through the pentose phosphate pathway is limited, and NAPDH is rapidly depleted.
This leads to severe oxidative stress; red blood cells are particularly affected. 50% or more of a person’s red blood cells may be destroyed– this condition is called hemolytic anemia.
Substances that can cause hemolytic anemia in affected individuals:
primaquine: antimalarial drug
methylene blue: antimalarial drug, tissue stain
sulphonamides: antibacterial drugs
nalidixic acid: antibacterial drug
trinitrotoluene: explosive
Fava beans
![](https://s3.amazonaws.com/brainscape-prod/system/cm/051/688/148/a_image_thumb.png?1659410369)
Regenerative phase: overview
Ribulose 5-phosphate is isomerized into ribose 5-phosphate or epimerized into xylulose 5-phosphate. These two molecules feed into the regenerative phase of the pentose phosphate pathway.
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Ribose 5-phosphate can exit the pentose phosphate pathway and be used for nucleotide synthesis.
Xylulose 5-phosphate is a transcriptional regulator
What are the two main enzymes of the regenerative phase of the pentose phosphate pathway?
What is the goal of the reactions?
The two key enzymes of the regenerative phase are transketolase and transaldolase. Transketolase vitamin B1, thiamin pyrophosphate, TPP, as cofactors.
Transketolase transfers two carbon groups.
Transaldolase transfers three carbon groups.
The goal of these reactions is to allow the five carbon sugar to be turned into glycolysis intermediates in situations when nucleotide synthesis is not required.
When nucleotide synthesis is required, the reverse reactions convert glycolysis intermediates into five carbon sugars.***
Transketolase
taking 2 carbons and moving them around.
trans aldolase reaction..
Moving 3 carbons around..
Role of xylulose 5 - phosphate as a transcription regulator
trans regulation is indirect and by ChREBP
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What is ChREBP
Residues with phophates.. serine and thrionene* these are regulators of th etranscriptional regulation.
PKA (what is it inhibited by? activated by) activated by glucacon (cAMP)
Its role is to regulate transcription of genes that store carbohydrates as fat…
The charbohydrate resoponse element binding protein (ChREBP) is a transcription factor. ChREBP’s nuclear localization and transactivation is inhibited by phosphorylation by protein kinase A (PKA) and adenosine monophosphate activated kinase (AMPK)
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