HMP Flashcards
why is HMP important?
- generates HMP, which are necessary for cholesterol, steroid, and fatty acid synthesis
- produces ribose sugar units which are important for nucleotide synthesis
- in RBCs, NADPH are used to regenerate the reduced form of the antioxidant glutathione, which protects from ROS
What are the two phases of the HMP? What occurs in each?
Oxidative - ribulose-5-phosphate is made
Non-oxidative - ribulose-5-phosphate gets converted into ribose-5-phosphate and many sugar interconversions occur such that we are left with either ribose-5-phosphate or another glycolysis intermediate.
What are some of the glycolysis intermediates that are made in the non-oxidative phase of the HMP?
Glyceraldehyde-3-phosphate
Fructose-6-phosphate
WHat are the two major enzymes involved in the non-oxidative phase?
Transaldolase and transketolase
- they catalyze transfer of 2C and 3C molecular fragments.
Which enzyme utilizes TPP (thiamine pyrophosphate)?
Transketolase
What is the regulation of the HMP?
Glucose-6-phosphate dehydrogenase is the regulatory enzyme. It essentially begins the HMP by going from G6P to the next step in HMP.
- negatively regulated - NADPH via competitive inhibition (short term)
- positively regulated - Insulin via up regulating transcription of glucose-6-phosphate (long term)
Wernicke-korsakoff syndrome
Defective transketolase in TPP binding that can cause a neuropsychiatric disorder.
- paralysis in eye movements
- abnormal gait
- decreased mental function
- severely impaired memory
What 5 pathways require NADPH?
- reductive biosynthesis
- Cytochrome P450 monooxygenase system
- phagocytosis by white blood cells
- synthesis of NO
- reduction of Hydrogen Peroxide
How is NADPH involved in phagocytosis?
When the microorganism is phagocytized into the lysosome, NADPH oxidase converts O2 into a superoxide radical, O2-, which is highly toxic to microorganism sand kills them off.
- The creation of this ROS is termed respiratory burst.
How is NADPH involved in NO production?
In the conversion of Arginine to Citruline, NADPH is oxidized into NADP+. NO is a byproduct of this reaction.
How is NADPH involved in the reduction of hydrogen peroxide?
It regenerates a reduced Glutathione peroxide through glutathione reductase and NADPH.
What is glutathione?
A tripeptide that is present in most cells that acts as an antioxidant to reduce hydrogen peroxide to water. However, it needs to be in the reduced form, but after each cycle it is oxidized. This is where NADPH comes in. It acts with glutathione reductase to reduce glutathione.
Glucose-6-phosphate dehydrogenase deficiency
We know that this is the enzyme responsible for starting the HMP pathway instead of glycolysis. So, if we have a deficiency in this, the HMP pathway doesn’t occur. Therefore, no NADPH is made. Therefore, we see hemolytic anemia due to inability to detoxify oxidizing agents.
- Causes oxidative damage to Hb, which causes the precipitation of Hb in the RBC. This results in small inclusions within the cell body known as Heinz Bodies.
- X-linked recessive
- protects against malaria
Heinz body
Small inclusions within the RBC due to oxidative damage to Hb.
What are the two major types of G6P deficiencies?
G6PD A- - African population, only moderate hemolysis, occurs in old RBCs, enzyme half life of 14 hours.
G6PD Mediterranean - severe hemolysis, in all RBCs, enzyme half life of a few hours.
