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B2 Biochem > Pentose Phosphate Pathway And NADPH > Flashcards

Pentose Phosphate Pathway And NADPH Flashcards

1
Q

What’s another name for Pentose Phosphate Pathway?q

A

Hexose MonoPhosphate (HMP) Shunt

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2
Q

PPP is a branch off of what pathway?

A

Glycolytic

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3
Q

PPP serves what two purposes? think about the other name.

A

Generation of NADPH (monophospate)

Generation of ribose, 5 carbon sugar (not a hexose)

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4
Q

The ribose generated from PPP with be used in what?

A

The synthesis of nucelotides (the five carbon sugar building block)

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5
Q

Will PPP always create both NADPH and ribose?

A

No, it can either one, both, or neither.

Dependent on needs of the cell.

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6
Q

In PPP, how much ATP is used/consumed?

A

None!

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7
Q

What are the two types of reactions in PPP?

A

Oxidative reactions and nonoxidative reactions

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8
Q

Irreversible reactions of PPP

A

Oxidative

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9
Q

Reversible reactions of PPP

A

Nonoxidative

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10
Q

Steps/reactions of PPP

A
  1. Dehydrogenation of G-6-P
  2. Hydrolysis of 6-phosphogluconate
  3. Oxidative decarboxylation of 6-phosphogluconate
    4-8: Interconversions of sugar molecules
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11
Q

Dehydrogenation of G-6-P

A

Step 1

Enzyme: g6p dehydrogenase (G6PH)

Rate limiting step

Major point of regulation

NAPH+ is a required coenzyme

NADPH is POTENT competitive inhibitor

Unregulated by insulin

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12
Q

What inhibits and upregulates step 1?

A

NADPH inhibits and Insulin upregulates

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13
Q

Hydrolysis to 6-phosphogluconate

A

step 2

Enzyme: 6-phosphogluconolactone hydrolase

irreversible

Produces one NADPH

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14
Q

Oxidative phosphorylation of 6-phosphogluconate

A

Step 3

Enzyme: 6-phosphogluconate dehydrogenase

Irreversible

Produces 1 NADPH

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15
Q

Interconversions of sugar molecules

A

Step 4-8

Enzyme: transketolase

Reversible steps

Interconverts sugars with 3 to 7 carbon atoms

Permit synthesis for ribose-5-p for nucleotide production

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16
Q

Transketolase

A

Enzyme for step 4-8, Interconversions of sugar molecules

Requires TPP

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17
Q

What is the significance of transketolase?

A

It is important in diagnosing thiamine deficiency

Done by measuring its activity in RBCs

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18
Q

What is the difference between NADH and NADPH?

A

There is a phosphate group on the ribose sugar of NADPH in the place of a hydroxyl group on a NADH

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19
Q

5 functions of NADPH

A

EERPS

Electron donor for reductive biosynthesis of FAs, cholesterol and steroids

Electron donor for neutralization of reactive O species (h202, superoxide, etc)

Provides reducing equivalents for cytochrome systems

Plays role in phagocytosis

Substrate for synthesis of NO

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20
Q

What is ROS?

A

Reactive oxygen species

21
Q

When are ROS produced?

A

During aerobic metabolism

Through reactions with drugs and toxins

When levels of antioxidants are diminished

22
Q

NADPH plays a key role in the neutralization of

A

ROS

23
Q

NADPH role in neutralization of ROS

A

Assists in the reduction of GSSG to become GSH

Substrate in Glutathion, major antioxidant system

GSH will become reoxidized to convert ROS into water

24
Q

NADPH role in the Cyt P450 System

A

Rxn:
R-H + O2 + NADPH + H -> R-OH + H20 + NADP+

Assists in cleaving O2 to create water and hydroxyl group on R group

By adding oxygen, the compound may be inactivated, made more soluble, or provide a reactive group for attachment of other compounds

25
Q

Cytochromal P450 monooxygenase systems:

Or Cyt P450 for short

A

Mitochondrial and Micosomal

26
Q

Cyt P450 in Mitochondrial system

A

Synthesis of steroids

27
Q

Cyt P450 in microsomal system

A

Detoxification of foreign compounds

28
Q

Mitchondrial Cyt P450 plays a key role in which tissues and organs?

A

Steroidogenic tissues (placenta, ovaries, testes, and adrenal cortex)

Liver

Kidney

29
Q

Mitochondrial Cyt 450 in steroidogenic tissues

A

Uses NADPH for synthesis of steroid hormones

30
Q

Mitochondrial P450 in the liver

A

Uses NADPH to synthesize bile acids and vitamins D3

31
Q

Mitochondrial Cyt P450 in the kidney

A

Converts vitamin D3 to its active form

32
Q

Where is the Microsomal Cyt P450 found?

A

Membranes of the smooth ER in liver cells

Detoxifies drugs toxins and other chemicals

33
Q

NADPH plays a role in phagocytosis through what molecules?

A

Neutrophils and macrophages in WBCs

34
Q

How does NADPH aid in phagocytosis?

A

The NADPH oxidase and myeloperoxidase are used to generate oxygen free radicals to aid in destruction of microorganisms

35
Q

What is Chronic Granulomatous disease?

A

rare and genetic

NADPH oxidase deficiency, not able to produce oxygen free radicals.

36
Q

What is NO?

A

NITRIC OXIDE

Not nitrous oxide. Idiot.

37
Q

NO is synthesized from…

A

Arginine, oxygen, and NADPH

38
Q

What is the biological role of NO?

A

Smooth muscle relaxant

Used by macrophages to generate free radicals to assist in killing microorganisms

Inhibits platelet aggregation

Functions as a neurotransmitter in brain

39
Q

G6PD Deficiency

A

inability to detoxify oxidizing agents

Gene is on the x-chromosome

One of most common single gene disorders

Most common in African, Mediterranean, and Asian

Some protecting against malaria (like sickle-cell and thalassemia)

11% of African Americans

40
Q

G6PD is symptomatic when..

A

There is an infection

There are drugs that produce an oxidative stress

Fava beans??

41
Q

Clinical manifestation of G6PD Deficiency

A

Almost exclusively in RBCs as an episodic hemolytic anemia in adults

Neonatal jaundice in newborns (increased production of unconugated bilirubin)

Other organs/tissues may be affected by hemolytic anemia

Shorten lifespan in severe form

42
Q

Only way to make NADPH in RBCs

A

HMP Pathway (PPP)

43
Q

NADPH production in cells other than RBCs

A

Other pathways contribute to production

44
Q

RBCs do not have a

A

Nucleus (or mitochondria)

45
Q

Since RBCs do not have a nucleus, they cannot:

A

Synthesize more G6PD to replace any that are lost, therefore is cannot be replaced during its short life cycle

46
Q

What is the life cycle of a RBC?

A

110 days, about

47
Q

Patient can overcome G6PD deficiency in RBCs if:

A

Oxidative stress is removed, since the RBCs can reproduce

48
Q

G6PD Deficiency can produce what characteristic on RBCs?

A

Heinz bodies, little precipitates of oxidized hemoglobin on the RBC (almost looks like a exterior nucleus-shaped cyst)

B2 Biochem (13 decks)

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