Pentose (aka Hexose Monophosphate Shunt) Flashcards
PPP consists of two phases: _____ reactions (irreversible) and _____ reactions (reversible).
Oxidative reactions (irreversible), Nonoxidative reactions (reversible)
_____ reactions go to glycolysis as a result.
Nonoxidative
NADPH is generated when ______ is oxidized to ribulose-5-phosphate. This is ______ reaction phase.
Glucose-6-phosphate, Oxidative reaction phase
The ______ is used in the reductive biosynthesis and detoxification.
NADPH
What are the biosynthesis pathways? (4)
Fatty acid, cholesterol, nucleotide, and neurotransmitter biosynthesis.
What are the two detoxification systems?
Reduction of oxidized glutathione, and cytochrome P450 monooxygenases.
Through which phase does the pathway catalyzes the interconversion of 3,4,5,6 and 7 Carbon sugars?
Nonoxidative phase
What are the substrates for 3,4,5,6 and 7 carbon sugars?
3- G-3-P, 4- Erythrose-4-phosphate, 5- Ribose-5-phosphate and xylulose-5-phosphate, 6- Fructose-6-Phosphate, 7- Sedoheptulose-7-phosphate
Which five-carbon sugar is the most important?
Ribose-5-phosphate
_____ is a component of RNA and DNA, as well as ATP, NADH, FAD, and coenzyme A
Ribose-5-phosphate
How many molecules of NADPH are generated in the conversion of glucose-6-phosphate into ribulose-5-phosphate?
2 NADPH
What is the rate-limiting enzyme in the irreversible (Oxidative reaction) pathway?
Glucose-6-phosphate dehydrogenase.
What is the stoichiometry for oxidative phase?
Glucose-6-phosphate+ 2NADP => Ribulose-5-phosphate+ 2NADPH
What is the product yield by enzyme ribulose-5-phosphate isomerase?
Ribose-5-phosphate (R5P)
What is the product yield by the enzyme ribulose-5-phosphate epimerase?
Xylulose-5-phosphate (Xu5P)
The pentose phosphate pathway and glycolysis are linked by ______ and ______
Transketolase and Transaldolase
Thiamine pyrophosphate (TPP) is a coenzyme for ______.
Transketolase
TPP is also a coenzyme to the ______ of the Pyruvate dehydrogenase complex.
E1 subunit
What are the products that are yield by the enzyme transketolase? What is the coenzyme for this enzyme?
Fructose-6-phosphate (F6P) and Glyceraldehyde-3-phosphate (GAP); Thiamin Pyrophosphate (PTT)
What is the first RL enzyme?
Glucose-6-phosphate dehydrogenase
What is the second RL enzyme?
Phospho-gluconate dehydrogenase
The two RL enzymes both yield, and are the only two enzymes that yields NADPH. T/F?
True
Which substrate makes DNA and RNA?
Ribose-5-phosphate
Which substrates are sent to glycolysis?
G-3-P and F-6-P
Glucose-6-phosphate is oxidized to____
6-Phosphoglucono-lactone
The RL enzyme Glucose-6-phosphate dehydrogenase (G6PD) is controlled by the substrate availability of _____
NADP+
When the cell consumes NADPH, the _____ concentration rises, increasing the rate of Glucose-6-phosphate dehydrogenase activity, thereby stimulating ____ regeneration.
NADP+
NADPH
____ enhances G6PD gene expression and therefore flux through the pathway increases in the well-fed state.
Insulin
NADPH is a high-energy molecule whose electrons are used in ________, rather than for the transfer to oxygen as is the case with NADH.
Reductive biosynthesis
What tissues are rich in pentose phosphate pathway enzymes?
Tissues that are heavily involved in fatty acid and cholesterol biosyntheses.
In the live __% of the glucose oxidation occurs via the pentose phosphate pathway.
30%
Tissues with active pentose phosphate pathways:
Liver, adipose tissue, mammary gland, adrenal gland, testes, ovaries, red blood cell
Function in Liver
Fatty acid and cholesterol synthesi
Functions in Adipose tissue
Fatty acid synthesis
Functions in Mammary gland
Fatty acid synthesis
Functions in Adrenal gland
Steroid synthesis
Functions in Testes
Steroid synthesis
Functions in Ovaries
Steroid synthesis
Functions in RBC
Maintenance of reduced glutathione
The generation of reactive oxygen species (ROS) Sequence:
Oxygen->Superoxide->Hydrogen peroxide->Hydroxyl radical (each ‘->’ has an electron being added)
Reactive oxygen species are formed continuously as by-products of aerobic metabolism, and they can cause serious chemical damage to ___, ___ and ___ in the cell’s membrane.
DNA, proteins, and unsaturated fatty acids
What is the body’s most powerful endogenous anioxidant?
GLUTATHIONE
What is the cofactor for glutathione peroxidase?
Selenium
Glutathione cycle uses what two enzyme?
Glutathione reductase, and glutathione peroxidase.
If G6PD is compromised, NADPH levels will___, and glutathione cannot be reduced resulting in H2O2 accumulation which will lead to the _____ of the cell’s membrane.
Fall
Destabilization
Cytochrome P450 (Monooxygenase system) incorporate one atom from molecular oxygen into an aliphatic substrate thereby creating a _____ group and generating a _____ product.
Hydroxyl group
Water soluble product
What is the function of Cytochrome P450 Mitochondrial system?
Function is to participate in the hydroxylation of steroids, a process that makes these hydrophobic compounds more water soluble. (Estrone to Estradiol)
What is the function of Cytochrome P450 Microsomal system?
Function is the detoxification of foreign compounds (xenobiotics).
Microsomal system is also found associated with the membranes of the _____.
Smooth ER (particularly in the liver)
Mitochondrial system is used by which organ to hydroxylate 25-hydroxycholecalciferol (Vit. D) to its biologically active form 1,25-dihydroxycholecalciferol?
Kidney
Microsomal system participates in the hydroxylation of xenobiotics to make them more water soluble, thus facilitating their excretion via the____ or ___.
Kidney or bile
What does Cytochrome P450 reductase use?
FAD, FMN
________ is a xenobiotic commonly produced from the burning of coal, from the combustion of tobacco, or from food barbecued on charcoal briquettes.
Benzo[a]pyrene
Benzo[a]pyrene, a weak ____, is metabolized by _____ (such as 1A1, 1A2, and 1B1) to a potent carinogen.
Carcinogen
Cytochrome P450’s
Benzo[a]pyrene loves to bind to___ and ___
Adenine, and guanine
Benzo[a]pyrene will put ___ groups on P450?
Hydroxyl groups
Sequence of leading to cancer
Activation of oncogenes. Inactivation of DNA repair genes. Inactivation of tumor suppressor genes. Inactivation of apoptosis genes. Cancer.
Cytochrome P450 2E1 also mediates the metabolism of ______
Acetaminophen (found in Tylenol)
If alcohol and acetaminophen are taken at the same time, does alcohol compete with acetaminophen for metabolism by Cyto P450 2E1?
Yes
When drinking, Cyto P450_____. What happens to NAPQI and GSH?
Acute NAPQI build up, and GSH will run out.
Acetaminophen causes____.
Lipofection
What is phase 1 detox?
CYP2E1
What is phase 2 detox?
GSH
If both detox are not working what would happen?
Cell death.
Phagocytosis and the Respiratory Burst using NADPH oxidase is performed by ____, _____, and _____.
Macrophages, neutrophils and monocytes
What is the Fenton Reaction?
Attachment of the pathogen to a phagocytic cell.
Ingestion of the microorganism.
Destruction of the microorganism via NADPH (Reducing agent) causes respiratory burst.
What are the substrates for Nitirc oxide synthase(NOS)?
Arginine, O2, and NADPH
What are the co-enzymes for NOS?
FMN, FAD, and tetrahydrobiopterin
Arginine+NADPH=?
Nitric oxide
Nitric oxide is a ______ with an average life span of 3to 10 secondds.
Free radical
What is Endothelial nitric nitric oxide synthase?
An endogenous vasodilator, where as nitroglycerine and Viagra will produce exogenous NO.
AKA Endothelium derived relaxing factor.
Neuronal nitric oxide synthase (nNOS) function?
Functions as a neurotransmiter in brain.
What is Inducible nitric oxide synthase (iNOS)?
Medeiates turmoricidal and bactericidal actions of macrophages.
What is Glucose-6-phosphate dehydogenase deficiency?
An X-linked inherited disease characterized by hemolytic anemia.
G6PD deficiency impairs the ability of an erythrocyte to form ____, resulting in hemolysis.
NADPH
G6PD deficiency is common, affecting more than 400 million people in the Mediterranean, Middle East, Southeast Asia, and tropical parts of Africa. Why is this?
Malaria
G6PD deficiency is a genetic mutation that will serve as a protection of?
Malaria
Does everyone has the same Km for G6PD?
No
People with G6PD deficiency has the risk of developing what?
Hemolytic anemia
Hemolytic anemia can be caused if exposed to? (3)
Significant infections
Patients treated with peroxide generating drugs such as sulfa antibiotics, the antimalarial drug Primaquine or the ANTIPYRETIC ACETANILIDE.
Ingestion of fava beans.
Significant infections: The inflammatory resonse to infection results in the generation of peroxides in macrophages, which can diffuse from the macrophages into the erythrocytes and cause______.
Oxidative damage
What is Favism?
Ingestion of fava beans, a dietary staple of the Mediterranean, can cause hemolytic anemia.
What molecule is found in Fava bean that acts as an antimalarial drug?
Divicine