10/18 - Hexose Monophosphate Pathway

HMP

What is the abbreviated term for the alternate pathway used for glucose oxidation that produces NADPH and uses oxidative and non-oxidative steps?

pentose phosphate pathway, HM shunt, 6-phosphogluconate pathway

What are three other names which all refer to the HMP?

NADPH, pentose phosphates

The HMP produces what reduced coenzyme and three of what molecules?

Ribose-5-phosphate, Ribulose-5-phosphate, xylulose-5-phosphate

What are the three different pentose phosphates produced by the HMP?

Cytosol

The enzymes for the HMP are found in what region of all cells?

oxidative, non-oxidative

What are the two major stages of the HMP?

oxidative

Which of the two HMP stages involves irreversible reactions?

non-oxidative

Which of the two HMP stages involves reversible reactions?

fatty acids

Liver, adipose, and lactating mammary gland tissues require NADPH for synthesis of what?

steroid hormones

The adrenal cortex, ovaries, testes, and placenta require NADPH for the synthesis of what?

Hydroxylation

What types of reactions are used by adrenal cortex, ovaries, testes, and placenta to synthesize steroid hormones from cholesterol?

Erythrocytes

In which cells is NADPH required for the glutathione reduction process to protect against oxidative damage?

WBCs, macrophages

In which two cell types is NADPH required for killing phagocytised bacteria?

Thyroid

What non-steroid hormone produced by its own gland requires NADPH to be synthesized?

G6P DH, lactonase, 6-phosphogluconate DH

What are the three enzymes of the oxidative section of HMP?

G6P DH, 6-phosphogluconate DH

Which two enzymes of the oxidative section of the HMP produce/reduce NADPH?

G6P DH

Which enzyme of the oxidative section of the HMP is the rate-limiting step for the whole pathway?

6-phosphogluconate DH

Which enzyme in the oxidative HMP produces CO2?

glucose-6-phosphate

What is the primary substrate for the HMP going into the oxidative section?

G6P DH

What enzyme converts glucose-6-phosphate to 6-phosphogluconolactone and produces NADPH? It is the rate-limiting step.

Lactonase

Which enzyme converts 6-phosphogluconolactone to 6-phosphogluconate by adding water and is also called 2-6-PGL hydrolase?

6-phosphogluconate DH

What enzyme converts 6-phosphogluconate to ribulose-5-phosphate and produces NADPH and CO2?

Ribulose-5-phosphate

What is the end intermediate of the oxidative section of the HMP?

NADP+

What will allosterically activate glucose-6-phosphate DH?

NADPH

What will allosterically inhibit glucose-6-phosphate DH?

Insulin

What hormone will stimulate upregulation of Glucose-6-phosphate DH?

No

Does the non-oxidative section of the HMP produce NADPH?

No

Does the HMP produce or use ATP?

Transketolase

Which enzyme of the non-oxidative HMP will transfer 2 carbons?

Transaldolase

Which enzyme of the non-oxidative HMP will transfer 3 carbons?

ribose-5-p isomerase

What enzyme will convert ribulose-5-phosphate to ribose-5-phosphate in the HMP?

phosphopentose epimerase

What enzyme will convert ribulose-5-phosphate to xylulose-5-phosphate in the HMP?

nucleic acids

Ribose-5-phosphate can be removed from the HMP for the synthesis of what?

glyceraldehyde-3-p, fructose-6-P

What two intermediates will be produced from the actions of transketolase and transaldolase and will be removed to go into the glycolytic pathway?

Recycled

In tissues using HMP only for NADPH production, the intermediates will be what?

O2-, H2O2, OH-

What are the three reactive oxygen species, or ROS?

lipids, nucleic acids, carbs

What three molecule types are most harmed by reactive oxygen species?

Glutathione

What is the tripeptide molecule of glycine, cysteine, and glutamate that is oxidized to detoxify/reduce H2O2 and is present in most cells?

indirectly

Is NADPH directly or indirectly involved in the glutathione reduction process for H2O2?

Catalase

What is the enzyme that breaks H2O2 into O2 and water?

SOD

What is the enzyme that changes O2- to O2 or H2O2?

Glutathione peroxidase

What enzyme changes H2O2 to water using reduced glutathione?

NADPH

Glutathione, after being oxidized, requires what reduced coenzyme to be reduced so it can be reused?

C, E, A

What three vitamins can function as antioxidant scavengers using similar mechanisms to reduced glutathione?

ascorbic acid

What is an alternate name for Vitamin C?

tocopherols

What is an alternate name for Vitamin E?

Carotenoids

What is an alternate name for Vitamin A?

Cytochrome P450 Monooxygenase

What enzyme using NADPH converts O2 to H2O by placing one O in the substrate? It is involved in two systems based on location.

Mitochondrial

Which system of cytochrome P450 monooxygenase is used in synthesis of steroid hormones from cholesterol?

Steroid hormones

The Mitochondrial system of cytochrome P450 is used to synthesize what?

Microsomal

What system of cytochrome P450 is used to detoxify toxins, pesticides, organic compounds, and drugs?

detoxification

The microsomal cytochrome P450 system is used to do what to toxins, drugs, pesticides, and organic compounds?

oxidative burst

What is the term for the O2-dependent mechanisms used by leukocytes/macrophages/neutrophils to do phagocytosis?

Yes

Does oxidative burst by macrophages require ROS formation?

NADPH oxidase

What enzyme is used in oxidative bursts by phage cells to produce ROSs?

chronic granulomatous

What disease is a severe persistent infection caused by deficiency of NADPH oxidase and results in increased oxidant production?

endothelial

Nitric oxide is produced by what cells, such as vascular and lymphatic types and neural cells?

FMN, FAD, Heme, tetrahydrobiopterin

What are the four coenzymes used in the synthesis of nitric oxide?

Citrulline

Nitric oxide is produced in endothelial cells in the conversion of arginine to what?

guanylate cyclase

What enzyme in the cytosol is activated by nitric oxide diffusing into the vascular smooth muscle and forms cGMP?

cGMP

What molecule is made by cytosolic guanylate cyclase when activated by nitric oxide and causes smooth muscle relaxation?

nitroglycerin, nitroprusside

What are two examples of vasodilators that are metabolized to NO causing vasodilation and lower blood pressure?

endogenous

NO is considered what type of vasodilator as it is produced in the body itself from arginine?

bactericidal

Nitric oxide when produced combines with oxygen free radicals from macrophages to produce what compounds?

HMP

What is the only pathway to make NADPH in erythrocytes?

Heinz body

Deficiency in G6P DH will lead to shape change of RBCs/hemoglobin, forming what structures in the cells which will be cleared by macrophages?

malaria

G6P-DH deficiency can be caused by a gene prevalent in locations with high rates of what parasitic disease?

oxidative stress

Those with G6P DH will be asymptomatic until what condition occurs which can be started by infection, oxidant drugs, or fava beans?

reticulocytes

A G6P-DH depletion can lead to hemolysis, and therefore a higher proportion of what immature RBCs in the blood?

Sedoheptulose-7-phosphate

Transketolase will add 2 carbons to ribose-5-phosphate to form what intermediate?

glyceraldehyde-3-phosphate

Transketolase will remove 2 carbons from xylulose-5-phosphate to form what intermediate?

erythrose-4-phosphate

Transaldolase will remove 3 carbons from sedoheptulose-7-phosphate to form what intermediate?

fructose-6-phosphate

Transaldolase will add 3 carbons to glyceraldehyde-3-phosphate to form what intermediate?

glyceraldehyde-3-phosphate

Transaldolase will remove 3 carbons from fructose-6-phosphate to form what intermediate?