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Biochemistry > HMP Shunt/Pentose Phosphate Pathway/Phosphogluconate Oxidative Pathway > Flashcards

HMP Shunt/Pentose Phosphate Pathway/Phosphogluconate Oxidative Pathway Flashcards

1
Q

From glycolysis,

Glucose is phosphorylated to Glucose 6 phosphate and will continue to Citric Acid Cycle or be shunted to

A

Pentose phosphate Pathway

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2
Q

Purpose of pentose phosphate pathway

A

Generate reducing power (Produce NADPH)

Make five carbon sugars (pentoses) Ribose-5-phosphate

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3
Q

Alternate pathway of glycolysis

Generates NADPH for fatty acid synthesis

Supplies ribose phosphate for nucleic acid synthesis

A

Warburg-Dickens Pathway

Phosphogluconate shunt

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4
Q

HMP also functions for

A

interconversion of sugar

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5
Q

Location of HMP pathway

A

Cytosol

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6
Q

Rate limiting enzyme of HMP shunt

Involved in 1st part of the pathway
Irreversible, Rate limiting enzyme

Yields NADPH

A

Glucose-6-phosphate dehydrogenase

G6PD

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7
Q

Reactants in Pentose Phosphate Pathway

A

NADP

Glucose-6-Phosphate

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8
Q

Products of HMP/PPP

A

NADPH (2 generated per glucose-6-phosphate)

Ribose (Pentose sugar)

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9
Q

Consists of two phases:

A

Oxidative phase

Non-oxidative phase

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10
Q

Oxidative phase involves generation of this product when glucose-6-phosphate is oxidized to ribose-5-phosphate

A

NADPH

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11
Q

Nonoxidative phase involves interconversion of 3,4,5,6 and 7 carbon sugars to synthesize

A

Pentose sugars

For biosynthesis of nucleotide
Production of excess ribose-5-phosphates
Interconversion of sugars

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12
Q

Sugars that interconvert

A

Pentose
Hexose
Triose

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13
Q

The main product of the pentose phosphate pathway is

A

Ribose-5-phosphate

(2) NADPH

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14
Q

Enzymes involved in oxidative phase

A

Glutathione reductase
Transketolase
Transaldolase

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15
Q

PPP is highly active in

A

Fatty acid and steroid synthesizing tissues

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16
Q

Tissues with active pentose phosphate pathways

A

RBCs for maintenance of reduced glutathione
Adrenal for steroid synthesis
Testes for steroid synthesis
Adipose for Fatty acid synthesis
Mammary gland for Fatty acid synthesis
Ovary for steroid synthesis
Liver for Fatty acid and cholesterol synthesis

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17
Q

What type of tissue require PPP?

A

Rapidly dividing cells (bone marrow, skin, intestinal mucosa)

Tissues that carry out extensive FA synthesis (liver, adipose, lactating mammary gland) or cholesterol and steroid synthesizing hormones (liver, adrenal glands, gonads)

Erythrocytes, lens and cornea

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18
Q

Rate limiting step/enzyme for regulation of HMP

A

Glucose-6Phosphate Dehydrogenase

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19
Q

Glucose 6 Phosphate dehydrogenase is inhibited by

A

NADPH

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20
Q

Glucose 6 phosphate dehydrogenase is induced by

A

insulin

NADP

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21
Q

Involved in the 1st part of the pathway

Irreversible
Rate limiting step

Step 1

by enzyme

A

Glucose 6-phosphate -> Glucono 1,5 lactone 6P by

Glucose 6 Phosphate Dehydrogenase

NAD+ -> NADPH

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22
Q

Requires thiamine

Needed for interconversions of sugars

Only thiamine enzyme in RBC

Shunts Ribose-5-phosphate to Fructose-6-phosphate

A

Transketolase

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23
Q

Functions of NADPH

A

Source of electrons for biosynthesis of fatty acids and steroids

Maintenance of supply of reduced glutathione to protect against ROS

Bactericidal activity in PMNs

Supply for liver microsomal CYP450 monooxygenase cycle

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24
Q

X linked Recessive
Results in hemolytic anemia and symptoms of chronic granulomatous disease
Female heterozygotes have increased resistance to malaria

Deficiency of the rate limiting step of PPP

A

G6PD deficiency

Glucose 6 Phosphate dehydrogenase

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25
Q

Used in biosynthesis to make fatty acids, steroids and cholesterol

Respiratory burst in WBC

Detoxification

Free radical protection

A

NADPH reducing power

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26
Q

Lacks respiratory/oxidative burst

Recurring granulomas and pyogenic infection

A

Chronic Granulomatous Disease

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27
Q

NADH vs NADPH

NADH is important for production of

NADPH is important for

A

ATP

reductive biosynthesis

28
Q

Calvin Cycle

A

Significance

29
Q

No G6PD -> no HMP shunt -> no NADPH -> no reduced glutathione

A

Inc H202 in RBC
Dec lifespan of RBCs
Inc hemolysis
Hemolytic anemia

30
Q

G6PD produces

A

NADPH

6-Phosphoglucono-d-lactone

31
Q

Deficiency of G6PD causes

32
Q

Conversion of 6-phosphoglucono-d-lactone to 6-phosphogluconate is via

A

Lactonase *

Hydrolyzes 6-phosphogluconolactone to 6-phosphogluconate

33
Q

3rd Step:

6-Phosphogluconate undergoes oxidation and carboxylation to Ribulose-5-phosphate via the enzyme

A

6-phosphogluconate dehydrogenase

Generates NADPH

34
Q

6-phosphogluconate is oxidized and decarboxylated by the enzyme 6-phosphogluconate dehydrogenase to

A

D-ribulose 5 phosphate

NADPH

35
Q

Ribulose 5 Phosphate is converted to Ribose 5 phosphate by the enzyme

A

Ribose 5 Phosphopentose isomerase

In some tissues, the PPP ends at this point

36
Q

The second half of PPP is nonoxidative and is

A

Reversible
Produces ribose
Intermediates can reenter glycolysis

Interconversion of sugars

37
Q

Five carbon sugars
Used for many biological processes

RNA and DNA

38
Q

PPP and Glycolysis overlap

These intermediates can be exchanges between the pathway:

A

Glucose-6-Phosphate
Glyceraldehyde-3-Phosphate
Fructose-6-Phosphate

39
Q

Reduces Glutathione disulfide (GSSG) to the sulfhydryl form from GSH which is an important cellular antioxidant

Protects the RBC from oxidative stress

A

Glutathione reductase

40
Q

Glutathione reductase requires NADPH and the mineral

41
Q

Important for protection of RBC

A

Vitamin E alpha tocopherol

Selenium

42
Q

G6PD Deficiency leads to these clinical disorders

A

Decreased production of NADPH
Increased oxidized form of glutathione
Hemolytic anemia
Intake of antimalarial, fava beans

43
Q

Thiamine B1 deficiency in alcoholics

Deficient transketolase activity

A

Wernickes Korsakoffs

44
Q

Coenzyme of thiamine is

A

Thiamine Pyrophosphate TPP

45
Q

Broad beans common in Mediterranean diets

Presents as pallor, hemoglobinuria, jaundice and severe anemia 24-48h after ingestion of beans

46
Q

Caused by genetic deficiency of NADPH oxidase in WBCs

A

Chronic Granulomatous Disease

47
Q

Susceptibility to infections by catalase-positive organisms like Staphylococcus aureus, Klebsiella sp, Escherichia coli, Candida sp, Aspergillus

A

Chronic granulomatous disease

48
Q

CGD is confirmed by

A

Negative nitroblue tetrazolium test

49
Q

Enzyme that shunts Ribose-5-Phosphate to become Fructose-6-phosphate back to Glycolysis

A

Transketolase

50
Q

Conversion of malonyl coA to Fatty acid requires

51
Q

Patients with G6PD deficiency despite loss of Glucose 6 Phosphate dehydrogenase is still able to synthesize nucleotides because of

A

reversible conversion of Fructose-6-phosphate into Ribose-5-phosphate by the enzyme transketolase

52
Q

Ribulose 5 Phosphate is converted to Xylulose 5 phosphate by

A

Ribulose-phosphate-3-epimerase

Xylulose-5-phosphate can be shunted to Fructose-6-phosphate and proceed Glycolysis

53
Q

Ribose 5 phosphate can be used for pyrimidine and purine synthesis by the enzyme

A

5-phosphoribosyl-1-pyrophosphate

PRPP

54
Q

G6PD Deficiency manifests clinically as

A

Hemolytic anemia
Neonatal hyperbilirubinemia

After eating fava beans and drugs inducing hemolysis

55
Q

Glucose 6 Phosphate Dehydrogenase is stimulated by

A

Insulin

NADP

56
Q

Glucose 6 Phosphate Dehydrogenase is inhibited by

57
Q

Enzyme requires thiamine B1 needed for interconversions

Only thiamine enzyme in RBC

A

Transketolase

58
Q

HMP is particularly important in these organs

A 
Liver
Mammary glands (FA synthesis)
Adrenal cortex (NADPH dependent synthesis of steroids)
59
Q

NAD is different from NADP in the sense that the latter has

A

Phosphoryl group which allows it to interact with specific enzymes of reductive biosynthesis and not transfer of oxygen

60
Q

Gamma glutamyl cysteinyl glycine
Tripeptide thiol

Detoxifies hydrogen peroxide via glutathione peroxidase

A

Glutathione

Generation of reduced glutathione (protective) ie glutathione reductase using NADPH

61
Q

NADPH oxidase converts oxygen into superoxide

Rapid consumption of oxygen + formation of superoxide is known as the

Superoxide is converted into hydrogen peroxide by Superoxide Dismutase (SOD)

In the presence of MPO, peroxide + chloride are converted into Hypochlorous acid (HOCl the major component of household bleach)

Excess peroxide is neutralized by catalase or glutathione peroxidase

A

Respiratory burst

Neurrophil phagocytosis and oxygen dependent myeloperoxidase system for killing bacteria

62
Q

Oxidant drugs

A

Antibiotics (sulfamethoxazole)
Antimalarials
Antipyreric (Acetanilid only)

63
Q

Most commmon precipitating factor of hemolysis in G6PD

64
Q

Mutations causing the nonspherocytic hemolytic anemia occur are clustered in the

A

carboxyl end

G6PD Mediterranean Class I Severe

65
Q

Mutations causing milder forms of disease tend to be located at the

A

amino end

G6PD Class III A (prototype)

66
Q

Severe hyperuricemia or gout is caused by deficiency these enzymes

A

Glucose-6-phosphatase

Hypoxanthine-guanine-phosphoribosyltransferase HGPRT

67
Q

Severe hyperuricemia or gout is caused by elevated activity of this

A

5-phosphoribosyl-pyrophosphate synthetase PRPP

Biochemistry (32 decks)

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