Chapter 20 (Pentose Phosphate Pathway) Flashcards

Question

Production of NADPH (depth)

Answer 1

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

Answer 2

All irreversible -- all enzymes involoved are irreversible

Answer 3

Photosynthetic organisms use light to generate NADPH

Answer 4

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

Answer 5

PPP = crucial source of NADPH

Answer 6

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

Answer 7

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

Answer 8

Intramolecular ester between C1 crabanyl and C5 OH group

Answer 9

6 Carbon sugar acid

Answer 10

PPP and Glycolysis are linked by Transketolase and Transaldolase

Answer 11

1. Ribose-5-P 2. Xyulose-5-P

Answer 12

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

Answer 13

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

Answer 14

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

Answer 15

Formation of 2 Hexroses + 1 Triose from 3 pentose 3 C5 --> 2 C6 + C3

Answer 16

C5 + C5 --> C3 + C7 (Transketolase) C3 + C7 --> C6 + C4 (Transaldolase) C4 + C5 --> C6 + C3 (Transketolase) NET: 3 C5 --> 2 C6 + C3 ***ALL REVERSIBLE REACTIONS

Answer 17

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

Answer 18

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

Answer 19

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

Answer 20

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

Answer 21

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)

Answer 22

Flips configuration of OH at C3 --> needed for transketolase to function ***Catylyzed by Phsphopentose epimerase - Occurs in Calvin Cycle

Answer 23

Are reversible

Answer 24

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

Answer 25

C3 + C7 --> C6 + C4 GAP + Sedohetulose-7-P --> Fructose-6-P + Erthrose-4-P

Answer 26

C4 + C5 --> C6 + C3 Erthose-4-P + Xylulose-5-P --> Fru-6-P + GAP

Answer 27

Forms Fru-6-P + GAP ***Caylyzed by Transketolase

Answer 28

1. Epimerase 2. Transketolase 3. Transaldolase

Answer 29

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

Answer 30

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

Answer 31

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

Answer 32

Any ingested Ribose can be processed to glycolytic intermediates

Answer 33

Carbon skeletons of sugars can be rearranged to meet physiological needs

Answer 34

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

Answer 35

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 5. The ketose product is release and TPP is ready for another cycle ***Reversible rxn

Answer 36

TPP -- Transketolase = contains a tightly bound TPP

Answer 37

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

Answer 38

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

Answer 39

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

Answer 40

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

Answer 41

A schiff base -- formed between the crabanyl of ketose substrate and amino group pf Lysine at Active site of enzyme ***Requires Lysin

Answer 42

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

Answer 43

Stabilized by resonance

Answer 44

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

Answer 45

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

Answer 46

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

Answer 47

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

Answer 48

Responsible for Epinephrine and Norephinerphine

Answer 49

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

Answer 50

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

Answer 51

More sever version of Anemia

Answer 52

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

Answer 53

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

Answer 54

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

Answer 55

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)

Answer 56

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

Answer 57

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

Answer 58

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

Answer 59

The cytoplasmic concentration of NADP+

Answer 60

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

Answer 61

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

Answer 62

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

Answer 63

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

Answer 64

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

Answer 65

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

Answer 66

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

Answer 67

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

Answer 68

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

Answer 69

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

Answer 70

Affects the reproductive system

Answer 71

Too many vitamens - bad Example -- Increase vitamen D = Increase Ca2+ = Hypercalcemia = probelms with muscle + heart

Answer 72

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

Answer 73

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

Answer 74

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)

Answer 75

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

Answer 76

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

Answer 77

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

Answer 78

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

Answer 79

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

Answer 80

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

Answer 81

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

Answer 82

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

Answer 83

1. Glutamate 2. Cysteine 3. Glycine

Answer 84

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

Answer 85

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

Answer 86

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

Answer 87

GSSG + NADPH --> 2GSH + NADP+

Answer 88

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

Answer 89

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

Answer 90

Destruction of RBCs

Answer 91

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

Answer 92

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

Answer 93

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

Answer 94

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

Answer 95

Glu-6-P dehydrogenase definciencey = orotects against malaria

Answer 96

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

Answer 97

Parasites -- the parisites that cause disease need NADPH for growth

Answer 98

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

Answer 99

All aerobic animals that are highly active face the problem of damage by ROS ***More active = more susceptible to damage by ROS

Answer 100

When organisms are using carbohydrates only as fuel RQ = 1

Answer 101

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

Answer 102

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

Answer 103

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

Answer 104

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

Answer 105

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

Answer 106

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

Answer 107

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

Answer 108

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

Answer 109

2GSH + ROOH --> GSSG + H2O + ROH ***Uses glutathione as a reducing agent to eliminate peroxides

Answer 110

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

Answer 111

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

Answer 112

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

Answer 113

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