Pentose Phosphate Pathway Flashcards
The pentose phosphate pathway provides a major source of what compound?
NADPH
This pathway will also provide what sugar for the synthesis of ribonucleotides?
Ribose-5-phosphate
The oxidative portions of the pentose pathway have how many reactions that lead to the formation of ribulose-5-phosphate?
Three
The oxidative portion of the pentose pathway will produce what products (3) for each molecule of glucose-6-phosphate oxidized?
Ribulose-5-phosphate
CO2
two molecules of NADPH
This pathway is important for what 3 processes in the body?
- NADPH - dependent synthesis of fatty acids
- NADPH - dependent synthesis of steroid hormones
- Erythrocytes which require NADPH to keep glutathione reduced.
NADPH-dependent synthesis of fatty acids is important in what parts of the body?
Liver, mammary glands, and adipose
Synthesis of steroid hormones is important for what structures in the body?
Testes, ovaries, adrenal cortex, and placenta.
Where does the oxidative stage of the pentose pathway occur in the cell?
Cytosol
Glucose 6 phosphate dehydrogenase will catalyze an irreversible oxidation of glucose 6 phosphate into ______.
6-phosphogluconolacetone
The dehydrogenation of glucose 6-phosphate needs a specific coenzyme what is it?
NADP+
What will inhibit the dehydrogenation of glucose 6-phosphate?
NADPH
What hormone up regulates the dehydrogenation of glucose-6 phosphate to 6-phosphogluconolacetone? Is this step rate limiting?
Insulin - yes it is rate limiting
What does 6-phosphogluconaolacetone hydrolyze to?
6 phosphogluconate
6 phosphogluconate is than converted to what sugar? What other compounds are released during this run?
ribulose 5-phosphate, CO2 and NADPH
In what cell types does the non-oxidative reactions of the pentose pathways take place?
ALL cell types synthesizing nucleotides and nucleic acids.
The reversible reactions permit ribulose-5-phosphate to be converted to what 3 compounds?
- Ribose 5-phosphate
- fructose 6-phosphate
- glyceraldehyde 3-phosphate
How does NADP+ differ from NAD+?
The presence of a phosphate group on one of the ribose subunits.
The high energy electrons of NADPH will be used for what function in the cell?
Reducing equivalence
What reactive oxygen species (ROS) is formed from the partial reduction of molecular oxygen?
Hydrogen peroxide
The highly reactive species of free radicals can cause what type of damage to the body?
Damage to DNA, proteins, lipids leading to cellular damage and death.
What is present in most cells that can chemically detoxify hydrogen peroxide?
Reduced Glutathione, a tripeptide-thiol
What is Glutathione composed of?
Glutamate, cysteine and glycine
Once Glutathione is oxidized to detoxify hydrogen peroxide how is it rejuvenated?
NADPH with the enzyme glutathione reductase.
What does the breakdown of hydrogen peroxide by glutathione produce as end products?
2 water molecules and a dimerized glutathione
What is the main function of the mitochondrial cytochrome P450 monoxygenase system and where is it found in the cell?
Associated with the synthesis of steroid hormones. Found on the inner mitochondrial membrane.
More specifically, the P450 is used to hydroxylate intermediates for what biosynthetic process? Where especially does this occur in the body?
For the conversion of cholesterol to steroid hormones a process that make these compounds more water soluble.
- placenta, ovaries, testes, and adrenal cortex
In the liver what is the job of the P450 system?
To hyroxylate intermediates in bile acid synthesis, and the synthesis of Vit D3
What does the endoplasmic reticulum especially in the liver contain? What is it’s function?
Cytochrom P450 monooxygenase - to detoxify foreign compounds such as drugs, pollutants and pesticides.
Describe Phase 1 Metabolism
- Microsomal system hydroylates these compounds (drugs, pollutants…etc) using NADPH as the source of reducing equivalents.
- The hydroxylation may inactivate the compound and make them more soluble for excretion in the urine.
What takes place in Phase 2 Metabolism
- Adding glucuronic acid or other compounds at the hydroxyl group further inactivating and/or increasing the water solubility of the compound.
WBC can use what two types of methods to kill bacteria?
Oxygen dependent or non-oxygen dependent methods.
In the oxygen dependent system what molecule is created by the activation of NADPH oxidase located in the cellular membrane of the phagocyte?
Superoxide
What do we call the rapid consumption of the molecular oxygen that accompanies the creation of superoxide?
Respiratory burst
What does the body do with the superoxide?
Either converts it to hydrogen peroxide spontaneously or through an enzyme superoxide dismutase.
Superoxide can also spontaneously break down to what compound?
Hydroxy radical (OH)
Hydrogen peroxide can also be converted into what effective bacteria killing liquid when combined with chlorine?
Hypochlorous acid
What can lead to granulomatous disease?
Genetic deficiency of NADPH oxidase.
What is the pathology of granulomatous disease?
Some bacteria are not completely destroyed and severe chronic infection develops. Granulomas are formed that sequester bacteria.
What is an additional function of NADPH when it is combined with arginine and O2?
Synthesis of Nitric Oxide
What is the most common disease producing enzyme abnormality in humans affecting 1 out of 400 individuals?
Glucose 6-phosphate deficiency G6PD
G6PD is an inherited disease characterized by what pathology?
hemolytic anemia - which is caused by an inability to detoxify oxidizing agents.
What chromosome is G6PD linked to?
X
Why did G6PD develop?
It gave survival advantage to female carriers by giving resistance to falciparum malaria.
Diminished G6PD activity impairs the ability of the cell to do what essential metabolic process?
To form the NADPH that is essential for the maintenance of the reduced glutathione pools. The result is a decrease in cellular detoxification of free radicals and peroxides.
Glutathione also has an important role in proteins. Please explain.
Helps maintain the reduced states of sulfhydral groups in proteins including hemoglobin. Oxidation of these groups results in the denaturization of proteins.
What can trigger symptoms in G6PD in ppl who don’t normally show clinical symptoms?
Oxidant drug, fava beans or infection.
What drugs can induce hemolytic anemia?
Antibiotics, antimalarials, and antipyretics. AAA
