2- Pentose Phosphate Pathway Flashcards
What are the possible starting materials for the Pentose Phosphate Pathway (PPP)?
Glucose-6-phosphate
What are the functions of the Pentose Phosphate Pathway?
- Generation of NADPH for reactions in the cytosol
- Production of ribose-5-phosphate for nucleotide synthesis
- Providing an alternative to glycolysis as a means of metabolizing glucose
- The interconversion of pentoses and hexoses
What are the enzyme, substrate and product for the rate determining step of PPP?
The first step is the rate determining step.
Substrates: Glucose-6-phosphate + NADP+
Enzyme: Glucose-6-phosphate dehydrogenase
Products: 6-Phosphoglucono-delta-lactone + NADPH + H+
Is ATP or NADPH utilized or produced in the Pentose Phosphate pathway (PPP)? In what reactions?
2 NADPH is produced for each glucose-6-phosphate oxidized.
In the first reaction,
Glucose-6-Phosphate + NADP+ —> 6-phosphoglucono-delta-lactone +NAPH + H+ (via glucose-6-phosphate dehydrogenase)
In the third reaction:
6-phosphogluconate + NADP+ —> Ribulose 5-phosphate + NAPH + C2 (via 6-phosphogluconate dehydrogenase)
Describe how glucose -6-phosphate dehydrogenase deficiency can be related to hemolytic anemia.
The pentose phosphate pathway produces NADPH, which is necessary for regenerating glutathione disulfide into 2 glutathiones. Glutathiones react with peroxidases to prevent them from damaging erthyrocyte walls. However, a deficiency in glucose-6-phosphate dehydrogenase, the rate limiting step of the pentose phosphate pathway, would reduce the available NADPH to produce glutathiones.
The lack of glutathiones would cause peroxides to build up, damaging erythrocyte membranes. Also, Heinz bodies (cross-linking of hemoglobin) will reduce Hb flexibility, causing rupture when the now fragile erythrocytes pass through small vessels. The combination of these two outcomes will lead to acute hemolytic anemia, black urine, and increased urine flow. The effects will go away when new erythrocytes are produced.
In what tissues is the pentose phosphate pathway most active? In which part of the cell is it carried out?
PPP is most active in tissues that use NADPH or involved in high rate of nucleotide synthesis.
Tissues with high demands for NADPH are those involved in the biosynthesis of lipids or catecholamines. These include liver, adipose, lactating mammary, adrenal cortex, and nervous system.
Other tissues which require a reducing capability to avoid oxidative damage are erythrocytes and leukocytes.
Tissues with high rates of nucleotide synthesis include bone marrow, skin and gastric mucosa.
ALL parts of this occur in the cytosol, away from glycolysis
What tissues require NADPH for lipid and catecholamine synthesis?
liver, adipose, lactating mammary, adrenal cortex and the nervous system
What tissues require ribose phosphate for high rates of nucleotide synthesis?
bone marrow, skin and gastric mucosa.
These cells require ribose-6-phosphate for nucleotide synthesis and have a high turnover rate of cells.
What tissues require NADPH for protection against oxidative damage?
erythrocytes and leukocytes
In the pentose phosphate pathway, the transkeolase reactions require the factor ________.
thiamine pyrophosphate
What type of categories of enzyme reactions are utilized in the pentose phosphate pathway?
1) Oxidative reactions
2) Isomerization or epimerization reactions
3) reactions that require carbon-carbon bonds to be cleaved or formed
In PPP, which enzyme in the latter part requires thiamin?
phosphoenolpyruvate carboxykinase