The Hexose Monophosphate Pathway. Flashcards
What is the HMP pathway used for?
It is an alternative pathway for the oxidation of glucose.
What other names is the HMP pathway known as?
HMP pathway.
Hexose monophosphate shunt.
6-phosphogluconate pathway.
What are the products of the HMP pathway?
2 molecules of NADPH.
3 pentose phosphates.
What are the 3 pentose phosphates that are formed in the HMP pathway?
Ribose 5-phosphate.
Ribulose 5-phosphate.
Xylulose 5-phosphate.
What is ribulose 5-phosphate used for?
DNA and RNA synthesis.
What can NADPH be used form?
It can help form fatty acids and steroid hormones.
What will NADH help to form that will de-toxify the cell?
Reduced glutathione.
Where does the HMP pathway take place?
In the cytoplasm.
Where are all the enzymes for the HMP located?
In the cytoplasm.
What enzymes are used in the HMP?
Transaldolase.
Transketolase.
Several dehydrogenases.
What are the 2 phases that occur in the HMP pathway?
The oxidative phase.
The non oxidative phase.
What goes into the oxidative phase of the HMP?
Glucose 6-phosphate.
What comes out of the oxidative phase of the HMP?
Ribulose 5-phosphate.
What goes into the non-oxidative phase of the HMP?
Ribulose 5-phosphate.
What comes out of the non-oxidative phase of the HMP?
Ribose 5-phosphate.
What can ribulose 5-phosphate be used to form?
Ribose 5-phosphate.
It can be interconverted to carbohydrates and glycolytic/gluconeogenic precursors.
Are all the products from ribulose 5-phosphate formed in non oxidative reactions?
Yes.
Is any energy used in the HMP pathway?
No ATP or NADH are used in the HMP pathway.
The NADPH that is formed in the liver, adipose tissue, the lactating mammary gland will be used to synthesise what?
Fatty acids.
The NADPH that is formed in the adrenal cortex, ovaries, testes and the placenta will be used to synthesise what?
Steroid hormones and in hydroxylation reactions.
The NADPH that is formed in the erythrocytes will be used for what?
For the reduction of glutathione.
The NADPH that is formed in the white blood cells and
in macrophages will be used for what?
Phagocytose bacteria.
The NADPH that is formed in the thyroid will be used to synthesise what?
Thyroid hormones.
What are the 2 phases in the HMP pathway?
The oxidative phase and the non oxidative phase.
In what phase of the HMP are all of the reactions irreversible?
The oxidative phase.
In what phase of the HMP is NADPH formed?
The oxidative phase.
In what phase of the HMP are all of the enzymes dehydrogenases?
The oxidative phase.
What is the regulatory enzyme in the HMP pathway?
G-6-Phospahte dehydrogenase.
What happens in step 1 of the oxidative phase of the HMP pathway?
Glucose 6-phosphate is converted to 6-phosphogluconate.
What energy is created in step 1 of the oxidative phase of the HMP pathway?
NADPH.
What 2 enzymes are used in step 1 of the oxidative phase of the HMP pathway?
Glucose 6-phosphate dehydrogenase.
Phosphoglucolactone hydrolase (lactonase).
Is step 1 of the oxidative phase a regulatory step of the HMP pathway?
Yes.
What happens in step 2 of the oxidative phase of the HMP pathway?
A carbon is removed as CO2 from 6-phosphogluconate to form ribulose 5-phosphate.
What is a decarboxylation reaction?
When a C is removed from a molecule.
What energy is created in step 2 of the HMP pathway?
1 NADPH.
What enzyme is used in step 2 of the oxidative phase of the HMP pathway?
Phosphogluconate dehydrogenase.
Does phosphogluconate dehydrogenase require any coenzymes?
NADP+.
Mg2+.
What will activate glucose 6-phosphate dehydrogenase.?
Insulin.
What will stimulate glucose 6-phosphate dehydrogenase.?
NADP+.
What will inhibit glucose 6-phosphate dehydrogenase.?
NADPH (product).
Will glucose 6-phosphate dehydrogenase be activated in the well fed state or the fasting state?
In the well fed state as it is activated by insulin.
In what phase of the HMP are the reactions reversible?
The non oxidative phase.
In what phase of the HMP is ribose 5-phosphate formed?
The non oxidative phase.
In what phase of the HMP can be used to interconvert sugars to form glycolytic and gluconeogenic intermediates?
The non oxidative phase.
What phase of the HMP uses the enzymes transketolase and transaldolase?
The non oxidative phase.
Which phase of the HMP relies on a series of pentose phosphate interconversions?
The non-oxidative phase.
What is step 1 of the non oxidative phase of the HMP?
Ribulose 5-phosphate is converted to ribose 5-phosphate or to xylulose 5-phosphate.
What enzyme converts ribulose 5-phosphate to ribose 5-phosphate?
Ribose 5-phosphate isomerase.
What enzyme converts ribulose 5-phosphate to xylulose 5-phosphate?
Phosphopentose epimerase.
What are the 2 products of step of the non oxidative phase of the HMP?
Glyceraldehyde 3-phosphate.
Fructose 6-phosphate.
Can the products of non oxidative phase of the HMP enter any other pathways?
They can enter glycolysis or gluconeogenesis.
How are glyceraldehyde 3-phosphate and fructose 6-phosphate formed in the non oxidative phase of the HMP?
By a series of reversible inter-conversions.
What interconversions will transketolase carry out in the non oxidative phase of the HMP?
Erythrose 4-phosphate and xylulose 5 phosphate to fructose 6 phosphate and glyceraldehyde 3-phosphate.
Xylulose and riblulose to glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate.
What interconversions will transaldolase carry out in the non oxidative phase of the HMP?
Glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate to fructose 6 phosphate and erythrose 4-phosphate.
What co-enzymes are required by transketolase?
Thiamine pryophosphate (TPP).
How many carbons does transketolase move?
2.
How many carbons does transaldolase move?
3.
At what step will fructose 6-phosphate enter glycolysis?
Step 2.
At what step will glyceraldehyde 3-phosphate enter glycolysis?
Step 5.
Are all of the interconversions that are carried out in the non oxidative phase of the HMP pathway reversible or irreversible?
They are all reversible.
What are the 2 ways that cells can form NADPH?
The HMP pathway.
NADP+ dependent malate dehydrogenase.
What is the only way that red blood cells can form NADPH?
The HMP pathway.
What is oxidative stress in a cell?
When oxygen is broken down to form reactive oxygen species that can damage the cell.
Name some reactive oxygen species?
O2-.
H2O2.
OH.
How does NADPH help glutathione remove reactive oxygen species from the cell?
It helps glutathione reductase reduce glutathione.
Reduced glutathione can be used to convert H2O2 into H2O.
This will oxidise glutathione and it must be reduced by NADPH to carry on.
Which form of glutathione can be used to reduce ROS?
Reduced glutathione.
Which form of glutathione can not be used to reduce ROS?
Oxidised glutathione.
What are some vitamins that help remove ROS?
Vitamin A - Carotinoids.
Vitamin C - Ascorbic acid.
Vitamin E - Tocopherols.
What does the cytochrome P-450 monooxygenase system do?
They add 1 molecule of O2 to a ROS while the other is reduced to water.
The addition of O will make the ROS more soluble and it can be excreted in the urine.
Where is the P-450 monooxygenase system particularly important?
In the mitochondria and the microsomal system.
The P-450 monooxygenase system helps the body to metabolise what?
Drugs.
Does NADPH play a role in the monooxygenase system particularly important?
Yes.
How is NADPH used by phagocytes?
It helps them form an oxidative burst to kill foreign cells.
How can a deficiency in NADPH affect the immune system?
A deficiency in NADPH can result in many long term infections as it cannot be used to kill the invader.
What is chronic granulomatous disease?
When a deficiency in NADPH results in long term infections.
Does the synthesis of nitric oxide require NADPH?
Yes.
What coenzymes does the formation of nitric oxide require?
Flavin mononucleotide.
Flavin adenine di-nucleotide.
Heme.
Tetrahydrobiopterin.
What does the body use nitric oxide for?
To relax smooth muscles.
To prevent platelet accumulation.
It function as a neuro transmitter in the brain.
It can react oxygen free radicals to destroy bacteria.
NADPH can only be synthesised in RBCs by what pathway?
The HMP pathway.
What are the effects of H2O2 is in the red blood cells?
Severe oxidative stress that can kill the red blood cell.
How is H2O2 removed from red blood cells?
Reduced glutathione and glutathione peroxidase convert H2O2 to water.
How does a lack of NADPH affect reduced glutathione and glutathione peroxidase?
Without NADPH, glutathione peroxidase cannot be reduced and react with more ROS.
What can cause a build up of ROS in the RBCs?
Some drugs.
Fava beans.
What would a deficiency in G6-PD-H result in?
Hemolysis and anaemia.
What cells are particularly sensitive to a deficiency in G6-PD-H?
Red blood cells.
What are Heinz bodies
Dark spots in the RBC that form due to oxidative stress.
Why will a deficiency in G6-PD-H result in less NADPH?
Because it helps to catalyse the formation of NADPH.
What would a deficiency in G6-PD-H result in in new borns?
Neonatal jaundice and death.
A deficiency in G6-PDH primarily affects which populations?
African and Mediterranean populations.
People who have a deficiency in G6-PDH will be immune to what diseases?
Malaria.
When will a person who has a deficiency in G6-PDH show symptoms?
When oxidative stress occurs.
When will individuals with a deficiency in G6-PDH be susceptible to oxidative stress?
When exposed to oxidative drugs or fava beans.
What happens to red blood cells when NADPH is low?
Oxidative stress which will lead to lysis of red blood cells and peroxidation of membrane lipids.
