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BIOL304 > Chapter 20 (Pentose Phosphate Pathway) > Flashcards

Chapter 20 (Pentose Phosphate Pathway) Flashcards

1
Q

Pentose Phosphate pathway + ATP

A

Pentose Phophate pathway does not produce ATP

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2
Q

Parts of PPP

A

1 – Oxidative pathway (Generates NADPH)
2 – Non-Oxidative pathway (Interconversion of sugars)

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3
Q

Where is the Rate Limiting Step in PPP

A

In the oxidative Pathway

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4
Q

Where is NADPH produces in PPP

A

NADPH is produced in the Oxidative Reaction

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5
Q

PPP + other Pathways

A

PPP –> Glycolysis –> TCA –> ETC

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6
Q

Rate Limiting Enzyme in PPP

A

Glucophopsphate Dehydrogenase
**In the oxidative step
**Serves as control site for oxidative branch of pathway
***Most important regulatory factor = NADP+

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7
Q

Where does PPP occur

A

Occurs in the cytoplasm– both phases occur in the cytoplasm

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8
Q

Cofactor for Translocase

A

Vitamin B1
***Vitimin B1 definciey = have an inssue in the non-oxidative path
- Deficeinc ey in B1 –> Leads to problems in RBCs –> Causes Anemia + Hemolatic disease of newborn

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9
Q

Anemia

A

Have sickle cell (moon shaped cells) rather than circular cells = lose RBCs

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10
Q

Erythose-4-Phosphate

A

Erthrose site = electrolyte

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11
Q

Fate of GAP in PPP

A

GAP can go to Glycolysis
***If PFK 1 doesn’t work then PPP can join glycolysis to help make PPP (because it can make GAP and bypass PFK1)

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12
Q

Key product of PPP

A

NADPH

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13
Q

NADPH

A

The source of biosynthetic reducing power

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14
Q

What does PPP produce (general)

A

NADPH + 5 carbon sugars

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15
Q

Purpose of the first phase of PPP

A

The first phase of the PPP is the oxidative generation of NADPH
- Purpose is to generate NADPH
***First phase (Oxidative phase) makes NADPH

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16
Q

PPP Equation (NET)

A

Glu-6_P + 2NADP+ + H2O –> Ribulose-5-P + 2NADPH + 2H+ + CO2

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17
Q

Purpose of the second phase of PPP

A

Non-oxidative interconversion of a variety of Phsphorylated 3,4,5,6, and 7 carbon sugars
- Second phase makes carbon backbone molecules
- Excess 5 Carbon sugars can be converted into the intermediates of the glycolytic pathway

Example – 2nd phase can make GAP (3 Carbons)

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18
Q

Pathways that require NADPH

A

Overall = Synthesis + Detoxification

Synthesis:
1. Fatty Acid Biosynthesis
2. Cholesterol Biosynthesis
3. Neurotransmitter biosynthesis
4. Nucleotide biosynthesis
5. RBCs

Detoxification:
1. Reduction of Oxidized Glutathione
2. Cytochrome P450 monooxygenases

***NADPH = used in Reductive biosynthesis + protection against oxidative stress

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19
Q

Two forms Glutathione

A
  1. Oxidized
  2. Reduced
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20
Q

Pentose Phosphate Pathway

A

Glu-6-P –> Ribulose-5-P
- Ribulose5-P –> Xylulose-5-P or Ribose-5-P

***SLIDE 5

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21
Q

NADPH PRODUCTION

A

2 molecules of NADPH are generated in the conversion of Glucose-6-Phosphate –> Ribulose-5-P

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22
Q

What intiates the Oxidative phase

A

Glucose-6-P dehydrogenase
***Glucose-6-P dehydrogenase initiates the oxidative phase of the PPP
- INTIATED – by the conversion of Glucose-6-P –> Phosphoglucono lactone

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23
Q

Rate limiting step in PPP

A

Glucose-6-P –> 6-Phosphoglucono lactone

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24
Q

Glucose-6-P –> Phosphoglucono lactone

A

1st step of PPP (1st step of oxidattive poahe)
- Initiates PPP
- Rate Limiting step
- Irreversible
- In the process NADP+ is reduced to NADPH
***Enzyme = Glucose-6-P dehydrogenase

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25
Q

Production of NADPH (depth)

A
  1. First made in conversion of Glu-6-P to 6PGL
  2. Second is made in conversion of 6-PGL –> Ribulose-5-P + CO2
    ***Both made in oxidative phase
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26
Q

Reversibility of Oxidative Phase

A

All irreversible – all enzymes involoved are irreversible

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27
Q

Oxidative Phase of PPP (depth)

A
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28
Q

Photosynthetic organisms + NADPH

A

Photosynthetic organisms use light to generate NADPH

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29
Q

NADPH in all organisms

A

There is a path present in all organisms to generate NADPH –> helps cells meet NADPH needs in non-photosynthetic organisms + in non-photosynthetic tissues in plant

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30
Q

Use of PPP

A

PPP = crucial source of NADPH

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31
Q

How much NADPH is produced

A

2 molecules of NADPH –> done in conversion of Glu-6-P –> Ribulose-5-P

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32
Q

Oxidative Pahe depth

A
  1. Start with dehydrogenation of Glu-6-P at C1
    • Catylyzed by Glu-6-P dehydrogenase
      Glu-6-P –> 6-PGL
  2. 6-PGL is hydrolyzed
    • Catylyzed by Lactonase
      6-PGL –> 6-Phospho-gluconate
  3. Oxidative decarboxylation of 6-phosphogluconate
    - Produces Ribulose-5-P + NADPH

6-Phosphogluconate –> Ribulose-5-P

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33
Q

6-Phosphoglucono Lactone

A

Intramolecular ester between C1 crabanyl and C5 OH group

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34
Q

6-Phosphogluconate

A

6 Carbon sugar acid

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35
Q

Link between PPP and Glycolysis

A

PPP and Glycolysis are linked by Transketolase and Transaldolase

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36
Q

Potential Fates of Ribulose-5-P

A
  1. Ribose-5-P
  2. Xyulose-5-P
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37
Q

Ribulose-5-P –> Ribose-5-P

A

Ribulose-5-P can be isomerized to Ribose-5-P
***Catylyzed by Phosphopentose isomerase

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38
Q

Where can Ribose-5-P be used

A

Ribose-5-P and dertaibes of it = used in RNA + DNA + ATP + NADH + FADH2 + CoA
- Ribose-5-P = precurssor for many biomolecules

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39
Q

Making Ribose-5-P vs. NADPH

A

Ribose-5-P = precurssory for many biomolecules BUT many cells need NADPH for reductive biosyntehsis more than they need Robose-5-P to be encorporated into nucleotides

Example – Adipose Tissue + Liver + Mammary glands = need NADPH for Fatty Acid Synthesis – in this case Ribose-5-P is converted to GAP –> Fru-6P by transketolase and Transaldose

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40
Q

Net result of Transketolase and Transaldolase

A

Formation of 2 Hexroses + 1 Triose from 3 pentose

3 C5 –> 2 C6 + C3

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41
Q

Overall Reactions in Non-Oxidative Phase

A

C5 + C5 –> C3 + C7 (Transketolase)

C3 + C7 –> C6 + C4 (Transaldolase)

C4 + C5 –> C6 + C3 (Transketolase)

NET: 3 C5 –> 2 C6 + C3

***ALL REVERSIBLE REACTIONS

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42
Q

Reactions in Non-Oxidative Phase

A
  1. Formation of GAP and Sedoheptulose from 2 pentoses
    • GAP and sedpheptulose = reaction to from Fru-6-P and Erthrose-4-P
  2. Ribulose-5-P is converted into Xylulose (epimer of Ribulose)
    - Caytylyzed by Phosphopentose epimerase
  3. Tranketolase catylyzes synthesis of Fru-6-P and GAP from Erthrose-4-P and Xylulose-5-P

SUM of Reactions: 2Xylulose-5-P + Ribose-5-P –> 2Fru-6-P + GAP

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43
Q

Formation of GAP and Sedoheptulose

A

Formed from Xyulose-5-P + Ribose-5-P

Xylose-5-P + Ribose-5-P –> GAP + Sedohetulose-7-P
Overall: 2 five carbon sugares –> converted to a three and sevent carbon sugar
***Catalyzed by Transketolase

THEN – GAP and sedpheptulose = reaction to from Fru-6-P and Erthrose-4-P

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44
Q

Formation of GAP and Sedoheptulose (depth)

A

Xylulose-5-P = acts as donor of 2 Carbon unit

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45
Q

Substrates for Transketolase

A

Ketose substartes –
For Formation of GAP and Sedoheptiulose requires – ONLY in OH at C3 with configuration of Xylulose NOT the configuration of Ribulose

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46
Q

Xylulose-5-P

A

Epimer of Ribulose-5-P
***Substrate for transketolate –> transketolase requires that it is in the confisguation of Xyulose-5-P (C3 OH is in the Xyulose confirmation NOT the Ribulose confirmation)

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47
Q

Ribulose-5-P –> Xylulose-5-P

A

Flips configuration of OH at C3 –> needed for transketolase to function

***Catylyzed by Phsphopentose epimerase
- Occurs in Calvin Cycle

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48
Q

All enzymes in non-oxidative phase

A

Are reversible

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49
Q

Fate of GAP and Sedoheptulose-7-P

A

They react to form Fru-6-P and Erthrose-4-P
***Catylyzed by Transaldolase
- Occurs in calcin Cycle

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50
Q

Transaldolase

A

C3 + C7 –> C6 + C4

GAP + Sedohetulose-7-P –> Fructose-6-P + Erthrose-4-P

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51
Q

Where is Erythrose-4-P

A

In RBCs

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52
Q

Transketolase

A

C4 + C5 –> C6 + C3

Erthose-4-P + Xylulose-5-P –> Fru-6-P + GAP

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53
Q

Fate of Erthose-4-P + Xylulose-5-P

A

Forms Fru-6-P + GAP

***Caylyzed by Transketolase

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54
Q

Three enzymes in Non-oxidative

A
  1. Epimerase
  2. Transketolase
  3. Transaldolase
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55
Q

NET non-oxidative pathway

A

2Xylulose-5-P + Ribose-5-P –> 2Fru-6-P + GAP

***Shows the conversion of 3 C5 into the components of glycolitic and gluconogenic pathways

END NET – NET (of non-oxidative): 3Ribose-5-P –> 2 Fru-6-P + GAP
- net is due to conversion of Robose-5-P –> Xyluose-5-P

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56
Q

Ribose-5P –> Xylulose-5-P

A

Ribose-5P –> Xylulose-5-P – catylzed by sequuentia actions of:
1. Phosphopentose Isomerase
2. Phsphopentose Epimerase

Makes NET (of non-oxidative): 3Ribose-5-P –> 2 Fru-6-P + GAP

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57
Q

Fate of excess Ribose-5-P

A

Excess Ribose-5-P in PPP –> can be completley converted to glycolytic intermediates

58
Q

Ingested Ribose

A

Any ingested Ribose can be processed to glycolytic intermediates

59
Q

Conversion of carbon skelotons

A

Carbon skeletons of sugars can be rearranged to meet physiological needs

60
Q

Key in Transketolase and Transaldolase mechanisms

A

Both have a carbanion intermediate – both stabilize anionic intermediate in different ways

61
Q

Transketolase Mechanism

A
  1. Thiamine Pyrophophate (TPP) forms carbanion – C2 of TPP ionizes to give a carbanion
  2. The carbanion attacks the Ketose Substrate – the negitive charge of Carbon attaches the crabayl of ketose substarte
  3. A carbon-Carbon bond is cleaves – releases the aldose product + forms TPP joined to a two carbon fragment – the resulting addition compoun relases aldose pructu to yeild an activated Glyceraldgey unit
    • 2 Carbon fragment = Glycoaldehyde intermediate
      4l. The intermediate attacks the aldose substrate
    • The positiv charge on Nitrogen in thiazome ring acta a electron sink in develipment of activated intermediate
    • The cranyl o faldrose acceptor condenses with activated glyceraldhy init to form a keto
  4. The ketose product is release and TPP is ready for another cycle

***Reversible rxn

62
Q

Cofactor or Transketolase

A

TPP – Transketolase = contains a tightly bound TPP

63
Q

Transketolase (overall mechanism)

A

Transketolase trasnfers a 2 crabon glyceradlhy from a ketose donor to an aldrose acceptor

***Site of addition of 2 carbon unit is thiazole ring of TPP

***Transketolase = homologous to E1 subunit of Pyrivate Dehydrigenase complex

64
Q

Transketolase vs. Transaldoase mechanisms

A

Reactions by both enzymes = similar BUT distict
- Differencse = trasnketolase trasnfers a 2 carbion unit but trasnaldolase transfers a 3 carbon unit

***Each unit transientley attactches to enzyme in reaction –> thus the enzymes are examples of double replacement reactions

65
Q

Transaldolase reaction (mech overall)

A

Overall – Transaldoase transfers a 3 carbon dihydroxy acetone unit form ketose donor to aldose acceotor

66
Q

Prostetic group of Transaldolase

A

Doesn’t require a prostetic group RATHER a schiff base is formed between the crabanyl of ketose substrate and amino group pf Lysine at Active site of enzyme

67
Q

What is in active site of Transaldose

A

A schiff base – formed between the crabanyl of ketose substrate and amino group pf Lysine at Active site of enzyme

***Requires Lysin

68
Q

Transaldolase Mechanism

A
  1. From a chiff base – A schiff base forms between the enzyme and the ketone substate
  2. Shiff base is protonates –> bond between C3 and C4 is split
    • Protonation of the schiff base = results in release of aldose product
  3. Upon reportinateion – Aldose product is relased = leaves 3 carbon fragment bound to the enzyme
    • Negitive charge on shciff base crabaion = stabilized by resonance
    • Positive nitrogen atom of protinated shiff = acts as elecrton sink
      - release of the asldose product generates a subsituted enzyme intermediap
  4. Schiff base product is stable unit suitabke aldrose is bound
  5. the DHA = reacts with carbanyl group of aldole –> protination allows formation of new C-C bond
    • The three crabon fragment bound to enzyme adds to the aldose substrate
  6. Subsequnet deprotination occurs
  7. Following deprotination –> have hydrolysis of schiff base = release ketose product
69
Q

Stabilization of Carbanion in both reactions

A

Stabilized by resonance

70
Q

N in Schiff base vs Thiozole ring

A

Nitrogen in Protinated Schiff base (tansaldolase) = plays the same role as Thiozole ring (Transketolase)
- both electon sinks
- In botyh reactinos a group within intermediate reactions like crabanions in attacking the carbanyl to form a C-C bond

71
Q

Second name for PPP pathway?

A

HMP

72
Q

Sites of PPP

A
  1. Lactating mammary glands – FA and Steroid Synthesis
  2. Liver – FA and Steroid Synthesis
  3. Adrenal Cortex (Above Kidneys) – slows down during puberty
  4. Red Blood Cells
73
Q

Puberty + Adrenal Cortex

A

The Adrenal Cortex slows down during Puberty – the hypothalamus takes over to produce sex hormones
***Hypothalamus doesn’t stop until you die

74
Q

Adrenal Cortex Location

A

Adrenal cortex = sits above kidneys
- Adrenal Gland = Outside
- Medula = Inside

75
Q

Role of medula

A

Responsible for Epinephrine and Norephinerphine

76
Q

Adrenal Cortex issues

A

Get Adrenal Issue if there is chemical envirnment or if you drink alcholol or smoke cogaretttes
- If either the mom of dad smokes or drinks
***Adrenal cortex problems = an issue because get bad RBCs

77
Q

Glu-6-P dehydrogenase deficiency

A

Have decrease in NADPH in RBCs = get hemolytic Anemia due to poor RBCs defense against oxidizing agents
- Anmeia –> could lead to need to amputate
- X-linked recessive disease
- Most common human enxyme defciencey
- more common in African American people + people in the far east
- Increase Malaria resistnce because masquitoes don’t like the blood
- Have decrease in NADPH
- Have no oxidative phase = have no non-oxidative phase

78
Q

Beta-Thalamasssia

A

More sever version of Anemia

79
Q

Use of PPP for detoxification

A

Glu-6-P –> 6-PGL – uses an NAD+ – MEANS you need to regenerate NADP+ for path to continue

To regenrate NAD+ – GSSG –> GSH + GSH – regenerates NADP+ BUT ALSO in the process of reducing GSSH you can Oxidize H2O2 –> 2H2O
(Enzyme = Glutathione reductase)

***Couples the regernation of NADP+ with the oxidation of H2O2 to detoxofy H2O2 and make water

80
Q

What is the PPP coordinated with?

A

The PPP is coordinated with Glycolysis – escially regarding Metabolism of Glu-6-P

81
Q

What controls the rate of the oxidative phase PPP

A

The rate of the oxidative phase in PPP is controlled by the level of NADP+
***The most important regulatory factor is the concentration of NADP+

***The effect of NADP+ level on the rate of Oxidative phase ensures that NADPH is not being generated unless supply is needed for reduction biosynthesis or protection against oxidative stress has decreased

82
Q

What controls the flow of Glu-6-P

A

Need for:
1. NADPH
2. Ribose-5-P
3. ATP (The PPP doesnt require of make ATP BUT it is connected to pathways that do make ATP – conneceted to Glycolysis which does make ATP = ATP concentration affects PPP)

83
Q

Modes of the PPP

A
  1. Ribose-5-P need excess the need for NADPH
  2. The NADPH and Ribose-5-P needs are balanced
  3. More NADPH is needed than Ribose-5-P
  4. NADPH and ATP are both required
84
Q

Where do the modes of PPP come from?

A

The PPP can operate in four modes that result from the combinations of the oxidative phase + non-oxidative phase + glycolysis + gluconeogenesis

85
Q

Situation with Glu-6-P in glycolysios and PPP

A

Glu-6-P is metabolized by BOTH the PPP and glycolysis –> how is teh porcessing of it partitioned between the two paths?

Answer: The cytoplasmic concentration of NADP+ plays a key role in determining the fate of Glu-6-P

86
Q

What determines if Glu-6-P will be process via PPP or glycolysis?

A

The cytoplasmic concentration of NADP+

87
Q

How does NADP+ affct Glu-6-P dehydrogenase

A

Decrease in NADP+ = limites Glu-6-P dehydrogenase (limits dehydration) – because NADP+ is needed as electron acceptor

88
Q

Intensification on levels of NADP+

A

Decrease in NADP+ is intensified by the fact that NADPH competes with NADP+ for binding to enzyme

89
Q

When is NADPH needed/produced

A

NADPH is only generated if the body needs supply for reductive biosynthesis or protection against oxidative stress

***The efefct of using NADP+ levels as the rate determining for oxidative step ensures that NADPH is not being produced unless supply is needed for reductive biosythesis or protection against oxidative stress

90
Q

What controls the rate of the non-oxidative stage?

A

The non-oxidative phase is controlled primarily by the avalability of substrates

91
Q

Mode #1 (depth) – more ribose than NADPH needed

A

Example – rapidly dividing cells need Robose-5-P for synthesios of nucleotide precurssors of DMA
- Most of the Glu-6-P = converted to Fru-6-P and GAP by glycolysis
- Transaldolase and Tranketolase convert 2 molecules of Fru-6-P and 1 molecule of GAP into 3 molecules of Ribose-5-P

Glycolysis –> THEN TA and TK used Glycolytic intermediates to make Ribose-5-P

92
Q

MOde #2 (depth) - Need for NADPH and Ribose is the same

A

Glu-6-P is processed to 1 Ribulose-5-P + 2NADPH
- Ribulose-5-P is converted to Ribose-5-P

93
Q

Mode #3 (depth) - More NADPH is required than Ribose

A

Example - Fat tissues = required high NADPH for synthesis of Fatty Acids

Here – Glu-6-P is completeley oxidized to CO2 (Glycolysis + TCA)

Three groups of reactions are active:
1. Oxidative phase of PPP – get 2NADPH + 1Ribulose-5-P
2. Non-oxidative phase (TA + TK) – Ribulose-5-P is converted to Fru-6-P + GAP
3. Glu-6-P is resynthesized from Fru-6-P and GAP made by TA/TK –> THEN the Glu-6-P can be sued to make more NADPH

94
Q

NET PPP reactions (FIND OUT WHAT THIS IS SUM OF)

A

Glu-6-P + 12 NADP+ + 7H2O + 6O2 + 12NADPH + 12H + Pi

***Mean equation of Glu-6-P can be comlpetley oxidized for CO2 with gernation of NADPH –> in essence the ribose-5-P producved by PPP is recycled into Glu-6-P by TK and TA and enzymes in gluconogenic path

95
Q

Mode #4 (depth) – Both NADPH and ATP are required

A

Ribulose-5-P is produced by PPP –> converted to Pryruvate
- The Fru-6-P and GAP from Robose-5-P enter the glycolytic path –> get ATP

HERE – ATP and NADPH are both generated and 5 of teh 6 carbons of glucose end in Pyrruvate
- Pyruvate generated can be oxidized to generate more ATP OR it can be used for other things

96
Q

Tissues with Active PPP

A
  1. Adrenal Gland – Steroid Synthesis
  2. Liver –> FA and Steroid Synthesis
  3. Testes –> Steroid Synthesis
  4. Adipose Tissue –> FA synthesis
  5. Ovary –> Steroid Synthesis
  6. Mammary Gland –> FA Synthesis
  7. RBCs –> Maintenance of Reduced Glutathione
97
Q

Issue with taking extra Steroids

A

Affects the reproductive system

98
Q

Hypervitaminosis

A

Too many vitamens - bad

Example – Increase vitamen D = Increase Ca2+ = Hypercalcemia = probelms with muscle + heart

99
Q

Rapid Cell growth + PPP

A

The PPP is required for Rapid cell growth
- Rapidly divding cells need Ribose-5-P for Nucleic Acid Synthesis + NADPH for FA and memebrane syntehsis
- The glycolytic intermediates are diverted into PPP

100
Q

What do rapidly dividing cells need

A
  1. Robose-5-P –> for Nucleic Acid Synthesis
  2. NADPH –> For FA and memebrane synthesis

***All of these can come from PPP –> rapidly dividing cells need PPP

101
Q

Diversion of Glycolytic intermediates to PPP

A

DONE in rapidly dividing cells
***Done by expressing Pyruvate Kinase isozyme (PKM) AND by inhibiting the Triosphosphate isomerase by PEP (PEP is a substrate of PKM)

102
Q

Catalytic Activity of Pyruvate Kinase Isozyme

A

Low Catalytic Activity –> Makes bottleneck in Glycolytic pathway = glycolytic intermediates accumalate = they are then used in PPP = get NADPH and Ribose-5-p

103
Q

Rapidly dividing cells + PPP (depth)

A

Rapidly dividing cells = switch to aerobic glycolysis –> Glu-6-P and glycolitic intermediates are then used to generate NADPH and Ribose-5-P

104
Q

Rapidly dividing cells + PPP (depth)

A

Rapidly dividing cells = switch to aerobic glycolysis –> Glu-6-P and glycolitic intermediates are then used to generate NADPH and Ribose-5-P

105
Q

Key use of Glu-6-P dehydrigenase

A

Glu-6-P dehydrogenase plays a key role in protection against reactive oxygen species

106
Q

Glutathione use

A

Glutathione = helps prevent damage by ROS that are generated in the course of metabolism

107
Q

GSSH –> 2GSH

A

GSSH = Oxidized Glutathione
GSH = reduced Glutathione

GSSG –> 2GSH + NADP+
***Uses NADPH to reduce GSSG (GDDG is reduced while NADPH is oxidized)

***NADPH generated in the PPP by Glu-6-P dehydrogenase is required to maintain adequate levels of reduced Glutathione

108
Q

NADPH + reduced Glutathione

A

NADPH generated in the PPP by Glu-6-P dehydrogenase is required to maintain adequate levels of reduced Glutathione

109
Q

Cells with lower levels of Glu-6-P dehydrogenase

A

Cells with lower levels of Glu-6-P dehydrogenase are sensitive to oxidative stress

110
Q

AA needed for reduced Glutathione

A
  1. Glutamate
  2. Cysteine
  3. Glycine
111
Q

Glu-6-P dehydrogenase deficiency

A

People with deficiency have hemolysis
**Can occur from consumption of fava beans or fava pollen
**Makes people more sensitive to oxidative stress

112
Q

Use of GSH

A

GSH normally helps to control amounts of harmful Peroxides that are released by some agents
***Peroxides = ROS

Reaction – 2GSH + ROOH (Peroxide) –> GSSG + H2O + ROH
- Enzyme = Glutathione Peroxidase

113
Q

Role of NADPH in RBCs

A

In RBCs – the main role of NADPH is to regernate the reduced form of GSH
***because RBCs lack Mitochondria

Reaction – GSSG + NADPH –> 2GSH + NADP+
Enzyme = Glutathione Reductase

114
Q

Glutathione reductase

A

GSSG + NADPH –> 2GSH + NADP+

115
Q

Fava Beans

A

Contain a purine Glycoside that causes oxidative damage to RBCs – indicses hemolysis
- Can lead to Glu-6-P
dehydrogenase deficiency –> Can lead to hemolysis (“favism respoonse”
- Vicine = the pyromidne glycoside in fava beans
***Can get probelm from eating fava beans or from inhaling the pollen

116
Q

Favism Respnse

A

When eating fava leads to Glu-6-P dehydrogenase deficinecey = leaves to hemolysis
***More common in African Americans

117
Q

Hemolysis

A

Destruction of RBCs

118
Q

What is glutathione needed for?

A

Glutathione = needed for hemoglobine – Glutathione is required to maintain the normal sturctire of hemoglobin because it helps maintain the Cysteine residues in their reduced form (bonds to sulfar)
- No gluathione = no RBCs –> Anemia

119
Q

Low Glutathione

A

In the absence of Glutathione –> Sulfhydryl bonds occur among the hemoglobin molecules = forms agreggated (Forms Heinze bodies) –> Red blodd cells then Lyse
***Likley due to Glu-6-P dehydrogenase deficiency

120
Q

Heinz bodies

A

Agreggates of hemoglobin that form when have low Glutathione
***red dot in image = heinz body

121
Q

What tissue doesn’t have Nuceli

A

RBCs – RBCs survive 120 days then the old ones go through Apoptosis

122
Q

Advantage of Glu-6-P deficiency

A

Glu-6-P dehydrogenase definciencey = orotects against malaria

123
Q

How does Glu-6-P dehydrigenase deficiency prtect against malaria

A

By depriving the parisites of NADPH that they need in order to grow – because the PPP is compromised the cell and parasite die from oxidative damage

124
Q

What causes malaria

A

Parasites – the parisites that cause disease need NADPH for growth

125
Q

Humingbirds + PPP

A

Active animals that are susceptible to damage by ROS

Humingbirds have a high activinty in PPP (in both stages) –> allows them to use carb nector to produce ATP to power muscle activity – while doing so they can also make NADPH which protects against ROS

126
Q

Active animals + PPP

A

All aerobic animals that are highly active face the problem of damage by ROS

***More active = more susceptible to damage by ROS

127
Q

RQ for organisms that use carbs only as fuel

A

When organisms are using carbohydrates only as fuel RQ = 1

128
Q

Calculating RQ

A

CO2/O2

129
Q

Humingbirds RQ

A

When humingbirds us carbs as fuel RQ = >1
***The extra CO2 = comes from the PPP – they have a high activinty in PPP (in both stages) –> allows them to use carb nector to produce ATP to power muscle activity – while doing so they can also make NADPH which protects against ROS

130
Q

Human Altheletes comsuming carbs during excersize

A

Human athletes who consume carbohydrates during intense extended excerisize may also use the PPP for ROS protection

131
Q

Affect of ROS

A

ROS inflicts damage on all classes of macromolecules + can lead to cell death
- ROS = implicated in a number of human disease (ex. Diabetes)

132
Q

Reduced Glutathione (deopth)

A

Tripeptide with a free sulfhydryl group – combats oxidative stress by reducing ROS to harmless forms

WHEN REUDUCING ROS –> the gulathione is oxidized to GSSG – THEN THE GSSG must be reduced to regernate GSH

133
Q

Pamaquine

A

First synthetic Anti-malarial drug –> associated with the appearnace of severse and mysterious ailments – a few pateints developed sever symptoms (Black pee + Juandice + Hemglobin content in blood decrease –> in some casses teh destruction of red blood cells causes cell death)
- Drug indiced Hemolytic anemia

134
Q

Accutness of Glu-6-P dehydrogenase deficiency

A

More accute in RBCs – because they lack mitocondria = they have no means of generating reducing power

135
Q

Primaquine

A

Antimalarial drug closely to pamaquine that is widley used in malaria prone regions of the world

136
Q

How does pamaquine + Primaquin + fava cause hemolysis?

A

The chemicals are oxidative reagents that genrate peroxides
- Glu-6-P dehydrigenase is required to maintain glutathion levels in order to protect aginst oxidative stress – RBCs will be lowered is there is less reduced glutathione – and without dehydrgenase the peroxides wil cometinue to damage because no NADPH is being made to ereduce gluathione

137
Q

Glutathione Peroxidase

A

2GSH + ROOH –> GSSG + H2O + ROH

***Uses glutathione as a reducing agent to eliminate peroxides

138
Q

Role of NADPH in RBCS

A

Reduces the disulfide form of Glutathione to sulfhydryl form using Glutathione reductase

139
Q

Membranes damaged by heinz bodies

A

Membranes damaged by heinz bodies and ROS become deformed = the cell explodes

140
Q

What group has the more Glu-6-P dehydrigenase defciencey

A

African Americans – high frequencey suffest that the defeciencey mighty be advatgeghous under certain envrinmental conditions

ANSWER: the deficiency helps protect against malaria = it is in higher frequencey in places with malaria in the world

141
Q

Health conundrum about Glu-6-P dehydrigenase deficiencey

A

primiquine is commonly used as an efective anti-malarial drug BUT indricriminate use caises hemolysis in people with defeicney

SOLUTION – may to mane an anti-malarial vaccine

BIOL304 (4 decks)

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