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Biochem Block 2 > pentose phosphate > Flashcards

pentose phosphate Flashcards

1
Q

Names of pentose phosphate pathway

A
  • pentose phosphate pathway

- Hexose Monophosphate (HMP) shunt

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2
Q

Purposes of pathway

A
  • generation of NADPH
  • Generation of the 5-carbon sugar, ribose. to be used in the synthesis of nucleotides
  • can make both OR either. depends on needs of the cell
  • NO ATP IS PRODUCED OR USED
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3
Q

Dehydration of Glucose 6-P

A 
-step 1
Enzyme: Glucose 6-phosphate dehydrogenase (G6PD)
-RATE LIMITING
-IRREVERSIBLE
-NADP+ is required coenzyme
-NADPH is potent competitive inhibitor 
-expression is UPREGULATED by insulin
-PRODUCES FIRST NADPH
-flux through the pathway increases in absorptive state
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4
Q

Hydrolysis to 6-phosphogluconate

A

-Step 2
Enzyme: 6-phosphogluconolactone hydrolase
-IRREVERSIBLE
-NOT rate limiting

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5
Q

Oxidative decarboxylation of 6-phosphogluconate

A

Enzyme: 6-phosphogluconate dehydrogenase

  • IRREVERSIBLE
  • PRODUCES 1 NADPH
  • makes ribose 5-phosphate by removing the carbon
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6
Q

oxidative and nonoxidative steps

A

1-3=oxidative, irreversible

4-8=nonoxidative, reversible

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7
Q

Nonoxidative reversible reactions purose

A
  • interconverts sugars with 3 7-C atoms

- permits synthesis of ribose 5-P used for nucleotide production

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8
Q

Nonoxidative reversible reactions mechanism

A

Enzyme: Transketolase

  • requires TTP(from thiamine)
  • important in diagnosing thiamine dificiency
  • done by measurement of its activity in RBCs
  • TTP is supplied EXO so there is no thiamine intracellularly
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9
Q

Differences between NADPH and NADH

A
  • Everything is the same, but NADPH has a phosphate on sugar
  • both are electron carriers BUT NADH accepts and can donate to complex 1 in ETC
  • NADPH donates electrons to biosynthetic pathways
  • FUNCTIONS ARE NOT INTERCHANGEABLE
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10
Q

NADPH functions

A
  • electron donor for the “reductive” biosynthesis of fatty acids, cholesterol, and steroids
  • electron donor for the neutralization of reactive oxygen species
  • provides reducing equivalents for CYT P450 Monooxygenase
  • phagocytosis
  • substrate for synthesis of nitric oxide
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11
Q

What are the two functions of cyt P450 monooxygenase?

A
  1. biosynthesis of steroids(mitochondrial system)

2. detoxification of xenobiotics in liver (microsomal system)

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12
Q

Reactive oxygen species

A

-produced during aerobic metabolism, through reactions with drugs and toxins, when levels of antioxidants are diminished

increased levels of ROS can…

  • damage proteins and lipids
  • lead to apoptosis
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13
Q

NADPH Role in Neutralization of ROS

A

Tripeptide: gamma-Glutamylcysteinglycine:G-SH

  • Glutathion is the major antioxidant system
  • NADPH donates electron (reduced) to GSH and free radical turns into water and is no longer dangerous
  • then oxidized to GSSG and it repeats
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14
Q

Monooxygenase

A

-an enzyme that will incorporate 1 oxygen atom from molecular oxygen (creating an OH) group with the other oxygen being reduced to water

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15
Q

Mitochondrial system and NADPH

A
  • inner mitochondrial membrane
  • in steroidogenic tissues(placenta, ovaries, testes, adrenal) uses NADPH for synthesis of steroids
  • in liver: uses it to synthesize bile acids and Vitamin D3(digestion of lipids)
  • in kidney: converts vitamin D3 to its active form
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16
Q

Microsomal system and NADPH

A
  • smooth ER and liver cells
  • detoxification of drugs, toxins, and other chemicals
  • makes OH group that activate or inactivate drugs, make more soluble, , provide a reactive group for further attachment
17
Q

NADPH and phagocytosis

A
  • in white blood cells: neutrophils and macrophages(produced from monocytes)
  • generation of free radicals to aid in killing things
18
Q

MPO system

A

-combination of NADPH oxidase and myeloperoxidase are used to generate the oxygen free radicals

19
Q

NADPH oxidase deficiency

A
  • causes chronic granulomastous disease(CGS)
  • cant kill bacteria so they always have infections
  • bacteria is trapped from the rest of the body, but it wont die
20
Q

Nitric oxide

A
  • synthesized from arginine, oxygen, and NADPH
  • NOT NO3(laughing gas)
  • very short life
  • very reactive
  • it is a gas and can diffuse into cells easily
21
Q

NO and NADPH

A

Enzyme: NO synthase(3 enzymes that are products of different genes)

  • nNOS:neural tissues
  • eNOS: endothelial cells
  • iNOS: inducible
22
Q

NO enzymes and expression

A
  • nNOS and eNOS are constitutively expressed at constant levels
  • iNOS is only expressed under certain conditions
23
Q

Biological activity of NO

A
  • smooth muscle relaxant
  • nitroglycerin action is converted into NO to relax smooth muscle
  • used by macrophages to generate free radicals for phagocytosis
  • inhibits platelet aggregation
  • functions as a NT
  • considered a short lived secondary messenger
24
Q

G6PD

A
  • inability to detoxify oxidizing agents
  • gene is on X chromosome so boys more likely to get it
  • ONE OF THE MOST COMMON SINGLE GENE DISORDERS WORLDWIDE(400 million affected)
  • 1/4 males are affected
  • african and asian more likely
  • some protection against malaria
  • 11% amond blakcs
25
Q

G6PD precipitating factors

A
  • only symptomatic when experiencing oxidative stress
  • Infection: oxygen radicals generated by marcophages
  • drugs that produce an oxidative stress(chemo)
  • fava beans(not all for this)-favism
26
Q

Classes of G6PD

A 
class 1-very severe- (chronic)less that 10% enzyme activity 
class 2:severe(episodic)-less than 10%
class 3: moderate(10-60% of enzyme activity 
class 4: none-greater than 60% of enzyme activity
27
Q

Clinical manifestation of G6PD

A
  • almost exclusively in RBC as an episodic hemolytic anemia in adults
  • neonatal jaundice in newborns
  • effects on other organs due to hemolytic anemia
  • shorten lifespan in people with severer form
28
Q

WHY IN RBC???

A
  • the only pathway to make NADPH is HMP
  • other cell types have other pathways
  • RBC do not have nucleus so they cannot synthesize more G6PD to replace missing enzyme
  • most mutations that result in the deficiency affect the stability of the enzyme
  • most patients will be okay by making new RBC
29
Q

Heinz bodies

A
  • characteristic of G6PD deficiency
  • found in RBC
  • precipitates of oxidized hemoglobin
30
Q

Hemolytic anemia

A
  • seen with G6PD deficiency AND step 10 of glycolysis(PDH)

- Heinz bodies are only found with G6PD deficiency

Biochem Block 2 (11 decks)

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