Pentose phosphate Pathway

Question 1

Oxidative portion of pentose phosphate pathway

Answer 1

. 3 rxns that lead to formation of ribulose 5-phosphate, CO2, and 2 molecules of NADPH for each molecule of glucose-6-phosphate oxidized
. Important in liver, lactating mammary glands and adipose, testis, ovaries, placenta, and adrenal cortex
. NADPH-dependent

Question 2

Why do rbcs need NADPH

Answer 2

. Keep glutathione reduced

. Detoxify ROS

Question 3

Glucose-6-phosphate dehydrogenase (G6PD)

Answer 3

. Catalyzes irreversible oxidation of glucose 6-phosphate to 6-glucose 6=phosphogluconolactone
. NADP as coenzyme
. NADPH competitive inhibitor
. Insulin upregulates gene for G6PD and flux through pathway inc. in absorptive state

Question 4

Formation of ribulose 6-phosphate

Answer 4

. 6-phosphogluconolactone hydrolyzed by 6-phosphogluconolactone dehydrogenase
. Irreversible rxn
. Produces pentose sugar-phosphate, ribulose-5 phosphate, CO2, and NADPH

Question 5

Non-oxidative rxns in pentose phosphate pathway

Answer 5

. In all cell types that synthesize nucleotides and nucleic acids
. Catalyze interconversions of sugars containing 3-7 carbons
. Ribulose 5-phosphate converted to ribose 5-phosphate (nucleotide synthesis) or to glycolysis intermediates (fructose 6P, glyceraldehyde-3P)
. Most cells need NADPH and ribose-6P but not equally
. When demand for ribose incorporation to nucleotides is high these rxns can provide ribose-6P from glyceraldehyde-3P and fructose-6P in a sense of oxidative steps

Question 6

Cells w/ reductive biosynthesis have greater need for ____ than ____

Answer 6

. NADPH

. Ribose-6P

Question 7

Transketolase and transaldolase

Answer 7

. Convert ribulose 5-P to glyceraldehyde-3P and fructose-6P

Question 8

When NADP/NADPH ratio is low, it favors _____

Answer 8

Use of NADPH in reductive biosynthetic pathways

Question 9

When high NADP/NADPH ratio, it favors ____

Answer 9

Oxidative role for NAD

Question 10

NADPH

Answer 10

. Cellular source fo reducing equivalents for biosynthetic processes (fatty acid and cholesterol synthesis)
. High energy molecule
. Electrons used for biosynthesis not just O2 transfer (like NADH)
. Part of energy of glucose-6P is conserved in NADPH in pentose phosphate pathway

Question 11

Reaction to detoxify H2O2

Answer 11

. Catalyzes by glutathione peroxidase

. Forms oxidized glutathione (G-S-S-G) that doesn’t have protective properties

Question 12

How does cell regenerate G-SH?

Answer 12

. Rxn catalyzes by glutathione reductase using NADPH as source of reducing equivalents

Question 13

Dismutase and catalase

Answer 13

. Convert ROS to harmless products

Question 14

Antioxidant chemicals

Answer 14

. Ascorbic acid
. Vit. E
. Beta-carotene
. Reduce and detoxify reactive oxygen intermediates
. Reduce risk for certain cancers and chronic health problems

Question 15

Nitric oxide

Answer 15

. Mediator in many biological systems 
. Endothelium-derived relaxing factor causing vasodilation by relaxing smooth muscle 
. Acts as neurotransmitter
. Prevents platelet aggregation 
. Pays role in macrophage function

Question 16

Nitric oxide synthesis

Answer 16

. Arginine, O2 and NADPH substrate
. Enzyme: cytosol is nitric oxide synthase
. Coenzymes: Flavin mononucleotide (FMN), FAD, heme, and tetrahydrobiopterin
. Products: NO and citruline

Question 17

G6PD deficiency

Answer 17

. Hereditary disease (x-linked recessive) caused y point mutations
. Severity of disease correlates w/ amt fo residual enzyme activity in rbcs
. Hemolytic anemia caused by inability to detoxify oxidizing agents (impaired ability to make NADPH)
. Most common deficiency that produces human disease (>400 million people have it)
. High prevalence in Middle East, tropical Africa, and Mediterranean
. Inc. resistance to malaria caused by plasmodium falciparum

Question 18

Role of G6PD deficiency in RBCs

Answer 18

. Impairs ability to make NADPH
. Leaves pool of G-SH
. Dec. ability to detoxify free radicals causing damage and lysis fo cells
. Doesn’t have ribosomes so it can’t replace its supply of proteins
. Denatured proteins form insoluble masses (Heinz bodies) that attach to RBC membranes

Question 19

Precipitating factors in individuals w/ G6PD deficiency

Answer 19

. Usually asymptomatic

. Strong oxidant stress (drugs, favs beans, or infection) cans bring on anemia

Question 20

Class I G6PD

Answer 20

. <10% residual enzyme activity

. Very severe, chronic hemolytic anemia

Question 21

Class II G6PD deficiency

Answer 21

.<10% residual enzyme activity

. Severe, episodic hemolytic anemia

Question 22

Class III G6PD deficiency

Answer 22

. 10-60% residual enzyme activity

. Moderate

Question 23

Class IV G6PD deficiency

Answer 23

. >60% residual enzyme activity

. No symptoms