PPP pathway and G6PD deficiency Flashcards
what are other names for the pentose phosphate pathway?
hexose monophosphate shunt (HMP shunt) or 6-phosphogluconate pathway
where does PPP occur?
cytosol of cells
what is PPP and what is it NOT?
its a alternate pathway for metabolism of glucose - doesn’t produce ATP or any energy
what does the PPP produce?
provides NADPH + H
provides pentoses
what is NADPH produced in the oxidative pathway used for?
reductive biosynthetic reactions
what are the pentoses used for?
nucleotide synthesis for nucleic acid synthesis RNA and DNA!
where is the PPP active? - important
liver
lactating mammary glands
adipose tissue (provides NADPH for fatty acid biosyn)
adrenal cortex
testes/ovaries (NADPH for syn of steroid hormones)
RBCs (NADPH for red. of glutathione)
WBCs and macrophages (NADPH for phagocytosis)
what is the regulatory enzyme?
glucose 6-phosphate dehydrogenase
what uses TPP as a coenzyme in PPP?
transketolase
what can be used to test nutritional thiamine deficiency?
transketolase activity in RBCs
what is NADPH used for in the biosynthesis of?
reactions in fatty acid synthesis of steroid hormones
Synthesis of nitric oxide (NO)
what does NADPH reduce and detoxify?
hydrogen peroxide
what is used in the cytochrome P450 system?
NADPH
NADPH is used for phagocytosis in what?
WBCs
what produces superoxide free radicals in WBCs?
NADPH oxidase
what does deficiency of NADPH oxidase cause?
chronic granulomatousdisease characterized by severe persistent infections
•Infections result in increased production of oxidants
what is the major antioxidant in RBCs to detox hydrogen peroxide?
GSH
what can PPP defect cause in RBCs?
accumulation of hydrogen peroxide because of no GSH is being produced from NADPH and there for is damages the membrane and causes hemolysis in RBCs
what is the most common enzyme abnormality?
G6PD = x linked recessive- then PK
what can G6PD deficiency result in?
accumulation of free radials like hydogen peroxide
formation of denatured proteins as insoluble masses = heinz bodies
Hemolytic anemia
where does G6PD deficiency occur?
all cells, but more severe in RBC
what is the only way RBCs can get NADPH?
PPP
what exactly causes a deficiency in G6PD?
oxidative stress
infection
fava beans - Met
oxidant drugs = sulfa drugs - primaquine
what cells are especially vulnerable to G6PD deficiency?
old (senile) RBCs - they have no nucleus or ribosomes and cannot synthesize new enzyme
what does G6PD A- result in?
moderate form of G6PD deficiency
its a drug induced hemolytic anemia
when do patients have hemolytic manifestations? even if the sig. portion of young RBCs with G6PD A- have sufficient levels of the enzyme?
when expoed to one of the precipitating factors = infection, oxidant rug, fava beans
what are the precipitating factors(oxidants)?
infection
oxidant drugs = sulfa drugs/antimalarial drugs = primaquine
fava beans
in short, what does G6PD deficiency reduce ?
the levels of GSH levels - can’t break down oxidants!
how is nitric oxide synthesized?
nitric oxide synthase uses NADPH
oxygen
arginine
what is Glutathione reductase coenzyme?
NADPH
what is coenzyme of glutathione perioxidase?
Selenium
what two major pathways in the liver use NADPH for reductive biosynthesis?
fatty acid de-novo synthesis and cholesterol synthesis.
what enzymes need NADPH for drug metabolism?
The group of cytochrome P450 needs NADPH.
what is coenzyme of glutathione perioxidase?
Selenium
what two major pathways in the liver use NADPH for reductive biosynthesis?
fatty acid de-novo synthesis and cholesterol synthesis.
what two major pathways in the liver use NADPH for reductive biosynthesis?
fatty acid de-novo synthesis and cholesterol synthesis.
what enzymes need NADPH for drug metabolism?
The group of cytochrome P450 needs NADPH.
what enzymes need NADPH for drug metabolism?
The group of cytochrome P450 needs NADPH.
