Pentose Phosphate Pathway

Question 1

what are the molecules that make up the ROS (reactive oxygen species)?

what are the properties of each?

Answer 1

• O₂- (superoxide dismutase)
  
  • highly reactive
  • mostly seen at ECT
• H₂0₂ (hydrogen peroxidase)
  
  • weak oxidizing agents
  • lipid soluble
• OH⁰ / O⁰
  
  • high energy radiations - seen in X-rays
  • can split water into hydroxyl + hydrogen radicals

Question 2

which ROS is found at the mitochondrial ECT?

Answer 2

O₂^-

Question 3

which ROS is lipid soluble?

Answer 3

H₂O₂

Question 4

which ROS are found in X-rays? what can do they do?

Answer 4

OH⁰, O⁰

can split water into hydroxyl & hydrogen radicals

Question 5

what is glutathione?

• what is its function?
• what does it require to carry out its function?

Answer 5

an antioxidant

• function: neutralizes ROS hydrogen peroxide (H₂0₂) by converting it into water (H₂0)
• must be in its reduced form (2G-SH) to function, which requires
  
  • FADH₂
  • NADPH - made by oxidizing portion

Question 6

draw out the glutathione cycle

Answer 6

Question 7

what are the branches of the PPP?

what is the purpose of each?

Answer 7

• oxidative branch → provides NADPH. used for
  
  • FA synthesis
  • steroid synthesis
  • glutathione regeneration
• non-oxidative branch → provides ribose. used for
  
  • nucleotide / nucleic acid synthesis

Question 8

oxidative PPP branch

• uses what starting material?
• generates what final products? with what purpose?

Answer 8

• starting material: glucose-6-phosphate (glycolytic intermediate)
• final products:
  
  • NADPH: for glutathione cycle, FA / steroid synthesis
  • ribulose -5 - phosphate: enters non-oxidative PPP branch

Question 9

draw out the steps of the oxidative PPP branch

Answer 9

Question 10

non-oxidative PPP branch

• uses what starting material?
• generates what final products? with what purpose?

Answer 10

• starting materials: ribulose-5-phosphate (from oxidative PPP branch)
• finals products:
  
  • ribose - 5- phosphate: used for nucleic acid / nucleotide synthesis
  • glycolytic intermediates (G-3-P, F-6-P): are returned to glycolysis

Question 11

outline the steps of the non-oxidative PPP branch

Answer 11

• isomerase/epimerase rxn:
  
  • two ribulose-5-phosphate molecules converted two
    
    • ribose-5-P (isomerase rxn)
    • xylulose-5-P (epimerase rxn)
• 1st transketolase rxn:
  
  • ribose-5-P + xylulose-5-P → glyceraldehyde 3-P+ sedoheptulose-7-P
• transaldolase rxn:
  
  • glyceraldehyde-3-P + sedoheptulose-7-P → erythrose-4-P+ F-6-P
• 2nd transketolase rxn:
  
  • erythrose-4-P + xyulose-5-P → glyceraldehyde-3-P + F-6-P

Question 12

the 1st step in the non-oxidative PPP branch requires

• what reactants
• what products
• what enzymes
• what cofactors?

Answer 12

• reactant: ribulose-5-P
• two enzymes used to make two products:
  
  • isomerase → ribose-5-P
  • epimerase → xyulose-5-P
• cofactors - n/a

Question 13

ribose 5-P isomerization

• requires what enzyme?
• involves what biochemical changes?
• produces what product?

Answer 13

• phospho-pentose isomerase
• a ketone group (in ribulose) is converted to a aldehyde group (ribose)

Question 14

ribose 5-P epimerization

• requires what enzyme?
• involves what biochemical changes?
• produces what product?

Answer 14

• phosphopentose epimerase
• the orientation of an OH group is changed from the right in ribulose to left in xyulose

Question 15

non-oxidative PPP - after ribose-5-P and xyulose-5-P are generated, what is the next step?

Answer 15

the first transketolase reaction

Question 16

the first transketolase reaction of the non-oxidative PPP branch involves:

• what reactants
• what products?
• what enzymes?
• what co-factors?
• what key biochemical changes?

Answer 16

• enzyme: transketolase
• co-factors: TPP (Vitamin B1)
• biochemical change: transfer of 2-carbon unit from a ketose group (xyulose-5-P) to a aldose group (ribose-5-P)

Question 17

non-oxidative PPP - after glyceraldehyde-3-P and seo-heptulose-7-P are made, what is the next step?

Answer 17

the transaldolase reaction

Question 18

the transaldolase of the non-oxidative PPP branch involves:

• what reactants?
• what products?
• what enzymes?
• what co-factors?
• what key biochemical changes?

Answer 18

• enzymes - transaldolase
• coenzymes - n/a
• biochemical changes: a 3 carbon unit is transferred from a ketose (sedoheptoulose-7-P) to a aldose (glyceraldehyde-3-P)

Question 19

non-oxidative PPP - after erythrose-4-P and F-6-P are made, what is the next step?

Answer 19

• F-6-P: fed into glycolysis
• erythro-4-P: enters second ketolase reaction

Question 20

the second transketolase reaction of the non-oxidative PPP branch involves:

• what reactants?
• what products?
• what enzymes?
• what co-factors?
• what key biochemical changes?

Answer 20

• enzymes - transketolase
• cofactors - n/a
• biochemical changes: a 2 carbon group is transferred from a ketose (xyulose-5-phosphate) to a aldose (erythrose-4-phosphate)

Question 21

ribose-5-phosphate

• is made by what reaction?
• is what kind of compound?
• can enter what pathways?

Answer 21

• made by 1st step of non-oxidative PPP: isomerization reaction
• is a aldose
• can either
  
  • continue with non-oxidative PPP by entering 1st transketolase rxn, or
  • enter nucleic acid / nucleotide synthesis pathway

Question 22

what is true of both transketolase rxns non-oxidative PPP?

Answer 22

• require transketolase enzyme
• involve xyulose-5-phosphate as a substrate
• involve transfer of 2 carbon unit from a ketose to an aldose (ketose = xyulose)
• produce glyceraldehyde-3-P

Question 23

what is different about the transketolase reactions in non-oxidative PPP?

Answer 23

• 1st rxn:
  
  • requires TPP (Vit B12)
  • produces sedoheptulose-7-P
• 2nd rxn
  
  • produces fructose-6-P

Question 24

which non-oxidative PPP rxns produce glyceraldehyde-3-P?

Answer 24

• 1st transketolase rxn (step 2)
• 2nd transketolase rxn (final 4)

Question 25

which non-oxidative PPP rxns produce frucose-6-P?

Answer 25

* the transaldolase rxn (3rd step) * the 2nd transketolase rxn (4th step

Question 26

discuss the regulation of the oxidative branch of PPP

Answer 26

* rate limiting enzyme is **glucose-6-phosphate dehydrogenase,** which is * **tightly regulated by NADPH** (high NADPH inhibits G-6-P-DH)

Question 27

discuss the regulation of the non-oxidative branch of PPP

Answer 27

* non-oxidative branch is reversible * direction of path depends on need for NADPH vs need for ribose

Question 28

what are the three "modes" of the PPP can run in? what situations trigger which mode?

Answer 28

based on direction of non-oxidative path, oxidative path, and glycolysis * mode 1 - need for ribose = need for NADPH * all paths run in forward direction * mode 1 - need for ribose \> need for NADPH * non-oxidative path runs backwards: glycolytic products → ribose * mode 3 - need for NADPH \> need for ribose * glycolytic path runs backward: ends products → G-6-P → NADPH

Question 29

describe mode 1 of PPP when does mode 1 run?

Answer 29

need for ribose = need for NADPH all paths run forward

Question 30

describe mode 2 of PPP when does mode 2 of run?

Answer 30

non-oxidative branch runs backwards: glycolytic products → ribose-5-P runs when need for ribose-5-P \> need for NADPH

Question 31

describe mode 3 of the PPP when does mode 3 of the PPP run?

Answer 31

glycolysis runs backwards to generate G-6-P to made NADPH runs when need for NADPH \> need for ribose

Question 32

G-6-PDH deficiency * inheritance pattern * demographics * pathogenesis * presentation

Answer 32

* inheritance pattern = X-linked * demographics * almost exclusively male * AA * pathogenesis: **oxidative PPP branch disruption** * no oxidative PPP branch → NADPH → no glutathione regeneration → accumulation of ROS (H₂0₂) → **RBC lysis** → hemolytic anemia * often triggered by an increase in oxidative nature of environment * ex - quinolone * presentation - hemolytic anemia

Question 33

what drug can trigger anemia in a G-6-PDH deficient pt? how?

Answer 33

**quinilones** * are oxidative, an increase ROS in an RBC that without glutathione, a key anti-oxidant

Question 34

what does the glucaronic acid pathway produce?

Answer 34

* **glucuronic acid**: structural molecule, inc molecule solubility * **ascorbic acid:** Vitamin seen only in humans

Question 35

what are the uses of _glucuronic acid_?

Answer 35

* _structure component_ of * GAGs * glycoproteins * _increase solubility_ & thus the excretion of: * **bilirubin** (bilirubin glucuronic acid): toxic product of heme degradation * **xenobiotics**

Question 36

what does the glucuronic acid pathway require?

Answer 36

* glucose-6-phosphate (starting material) * 2 NADH