Pentose Phosphate Pathway Flashcards
Purpose of the pentose phosphate pathway
Alternate route for oxidation of glucose (other than glycolysis); does not give you energy, gives you NADPH in order to provide cell with ribose-5-phosphate
- Location of PPP (HMP shunt)
- Substrate?
- Two stages of PPP
- Cytosol
- Glucose-6-phosphate
- Oxidative/irreversible (first 3 steps); nonoxidative/reversible (rest of steps)
Results of the oxidative/irreversible stage
2 molecules of NADPH per molecule of glucose-6-phosphate (NADPH is not generated in nonoxidative stages) and synthesis of ribulose-5-phosphate and production of CO2
- First step of PPP
2. Does this happen in fasting or well fed state? Why?
- Glucose-6-phosphate to 6-phosphogluconolactone by glucose-6-phosphate dehydrogenase
- Well fed; if you were fasting, you would not have any glucose-6-phosphate so reaction could not occur
What inhibits this pathway?
Activates it?
Inhibited by high NADPH
Activated by high Insulin
What is mainly happening in the non-oxidative stages?
Series of sugar interconversion reactions — ribulose-5-phosphate to ribose-5-phosphate
Two main takeaways from nonoxidative stage
- Ribose-5-phosphate transfers 2 carbons via transketolase to get glyceraldehyde-3-phosphate
- Sedaheptulose-7-phosphate transfers 3 carbons via transaldolase to get erythrose-4-phosphate
- What does transketolase require in order to function normally
~2. Name 3 other enzymes that also require this for proper functioning
- TPP
2. PDH, alpha ketoglutarate dehydrogenase and branching amino acid dehydrogenase
What is used clinically to assess Thiamine levels to see if there is a deficiency ?
Erythrocyte transketolase activity (ETKA)
Overview: role of NADPH in:
- Liver
- Adrenal cortex
- Erythrocytes
- WBC
- Reductive biosynthesis means NADPH is going to provide hydrogen
1. Cholesterol and fatty acid synthesis / reductive biosynthesis
2. Steroid hormone synthesis / reductive biosynthesis
3. Maintains glutathione in reduced state / protection against H2O2 (reactive oxygen species)
4. NADPH oxidase / phagocytosis and lysis of bacteria
- Name 3 reactive oxygen species (bad unavoidable products of mitochondrial respiration)
- Two major disorders these cause
- What removes this?
- Superoxide radical, hydroxyl free radical, and hydrogen peroxide
- Cancer and atherosclerosis
- Antioxidants
- Name 3 nonenzymatic antioxidants
2. Name 3 enzymatic antioxidants
- Vitamin E, vitamin C and beta carotene
2. Catalase, glutathione peroxidase (RBCs) and superoxide dismutase
Importance of PPP for RBC
RBC can only produce NADPH by PPP
NADH is necessary to reduce glutathione and reduced glutathione is what prevents peroxides from accumulating
Gluthathione removes peroxides via?
What happens if there is an accumulation of peroxides in RBCs
GSH vs GSSG
Glutathione peroxidase
RBCs become rigid, weakened cell walls (due to hgb oxidizing to methemogloblin), concomitant hemolysis
GSH is reduced; GSSG is oxidized
Main function of the cytochrome P450 family of enzymes
Synthesizing and detoxifying reactions; making water soluble products so it can be excreted in urine (drugs/chemicals)
- Mitochondrial Cyt P450 mono oxygenase
2. Microsomal cyt P450 mono oxygenase
- Steroid hormone, hormone and vitamin D metabolism, cholesterol synthesis
- Smooth ER, detoxification
- A beneficial effect of ROS has to do with
- Main mechanism
- Why is it called a respiratory burst?
- NADPH and phagocytosis by WBC (respiratory burst)
- If you are are infected by bacteria, IgG will tag it and lysosome will attack. Once it is trapped, NADPH oxidase will produce superoxide H2O2 to kill bacteria
- HR and respiration will increase because WBC need high concentration of OO2 to fight bacteria (to make H2O2)
Genetic deficiencies of NADPH oxidase cause ____
How will this present clinically?
Chronic granulomatous disease (CGD)
Child that comes to clinic with chronic respiratory infections (will get sick even with the smallest exposure)
- NO pathway
2. Name 4 biological functions of Nitric Oxide (NO)
- Arginine reacts with NADPH to synthesize NO
- Relaxes smooth muscle, prevents clot formation, neurotransmitter in the brain, and released during inflammatory response to suppress it
Glucose-6-phosphate dehydrogenase deficiency
(G6PD)
- Affect in RBC
- Symptoms?
- Impairs the ability of RBC to form NADPH resulting in hemolysis
- Most are asymptomatic unless exposed by oxidative stress
Classifications of G6PD deficiency:
- Class 1
- G6PD mediterranean
- G6PD A-
- Rare and most severe / hemolytic anemia (very rigid RBCs)
- Enzyme show normal stability but scarcely detectable activity in all RBCs
- Enzyme is unstable but most of enzyme activity present in reticulocytes (immature RBCs) and younger RBCs
What can cause G6PD patients to experience hemolysis
3 classes of oxidant drugs that can cause this; what are they and name some examples
Infection, fava beans, and oxidant drugs
Antibiotics- sulfa, chloramphenicol
Antimalarials- primaquin
Antipyretics- acetanilid
How do G6PD patients with hemolytic anemia present?
Lab findings?
Pallor (anemia), slightly jaundiced sclera, and weak; recent travel to tropical regions
Low hematocrit, high blood levels of bilirubin, and hemoglobinuria
What are Heinz bodies?
In G6PD, oxidation of SH groups cause these insoluble masses to attach to RBC membrane
