HMP Shunt/Pentose Phosphate Pathway/Phosphogluconate Oxidative Pathway

Question 1

From glycolysis,

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

Answer 1

Pentose phosphate Pathway

Question 2

Purpose of pentose phosphate pathway

Answer 2

Generate reducing power (Produce NADPH)

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

Question 3

Alternate pathway of glycolysis

Generates NADPH for fatty acid synthesis

Supplies ribose phosphate for nucleic acid synthesis

Answer 3

Warburg-Dickens Pathway

Phosphogluconate shunt

Question 4

HMP also functions for

Answer 4

interconversion of sugar

Question 5

Location of HMP pathway

Answer 5

Cytosol

Question 6

Rate limiting enzyme of HMP shunt

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

Yields NADPH

Answer 6

Glucose-6-phosphate dehydrogenase

G6PD

Question 7

Reactants in Pentose Phosphate Pathway

Answer 7

NADP

Glucose-6-Phosphate

Question 8

Products of HMP/PPP

Answer 8

NADPH (2 generated per glucose-6-phosphate)

Ribose (Pentose sugar)

Question 9

Consists of two phases:

Answer 9

Oxidative phase

Non-oxidative phase

Question 10

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

Answer 10

NADPH

Question 11

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

Answer 11

Pentose sugars

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

Question 12

Sugars that interconvert

Answer 12

Pentose
Hexose
Triose

Question 13

The main product of the pentose phosphate pathway is

Answer 13

Ribose-5-phosphate

(2) NADPH

Question 14

Enzymes involved in oxidative phase

Answer 14

Glutathione reductase
Transketolase
Transaldolase

Question 15

PPP is highly active in

Answer 15

Fatty acid and steroid synthesizing tissues

Question 16

Tissues with active pentose phosphate pathways

Answer 16

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

Question 17

What type of tissue require PPP?

Answer 17

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

Question 18

Rate limiting step/enzyme for regulation of HMP

Answer 18

Glucose-6Phosphate Dehydrogenase

Question 19

Glucose 6 Phosphate dehydrogenase is inhibited by

Answer 19

NADPH

Question 20

Glucose 6 phosphate dehydrogenase is induced by

Answer 20

insulin

NADP

Question 21

Involved in the 1st part of the pathway

Irreversible
Rate limiting step

Step 1

by enzyme

Answer 21

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

Glucose 6 Phosphate Dehydrogenase

NAD+ -> NADPH

Question 22

Requires thiamine

Needed for interconversions of sugars

Only thiamine enzyme in RBC

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

Answer 22

Transketolase

Question 23

Functions of NADPH

Answer 23

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

Question 24

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

Answer 24

G6PD deficiency

Glucose 6 Phosphate dehydrogenase

Question 25

Used in biosynthesis to make fatty acids, steroids and cholesterol Respiratory burst in WBC Detoxification Free radical protection

Answer 25

NADPH reducing power

Question 26

Lacks respiratory/oxidative burst Recurring granulomas and pyogenic infection

Answer 26

Chronic Granulomatous Disease

Question 27

NADH vs NADPH NADH is important for production of NADPH is important for

Answer 27

ATP reductive biosynthesis

Question 28

Calvin Cycle

Answer 28

Significance

Question 29

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

Answer 29

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

Question 30

G6PD produces

Answer 30

NADPH | 6-Phosphoglucono-d-lactone

Question 31

Deficiency of G6PD causes

Answer 31

favism

Question 32

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

Answer 32

Lactonase * Hydrolyzes 6-phosphogluconolactone to 6-phosphogluconate

Question 33

3rd Step: 6-Phosphogluconate undergoes oxidation and carboxylation to Ribulose-5-phosphate via the enzyme

Answer 33

6-phosphogluconate dehydrogenase Generates NADPH

Question 34

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

Answer 34

D-ribulose 5 phosphate | NADPH

Question 35

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

Answer 35

Ribose 5 Phosphopentose isomerase In some tissues, the PPP ends at this point

Question 36

The second half of PPP is nonoxidative and is

Answer 36

Reversible Produces ribose Intermediates can reenter glycolysis Interconversion of sugars

Question 37

Five carbon sugars Used for many biological processes RNA and DNA

Answer 37

Pentose

Question 38

PPP and Glycolysis overlap These intermediates can be exchanges between the pathway:

Answer 38

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

Question 39

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

Answer 39

Glutathione reductase

Question 40

Glutathione reductase requires NADPH and the mineral

Answer 40

Selenium

Question 41

Important for protection of RBC

Answer 41

Vitamin E alpha tocopherol | Selenium

Question 42

G6PD Deficiency leads to these clinical disorders

Answer 42

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

Question 43

Thiamine B1 deficiency in alcoholics Deficient transketolase activity

Answer 43

Wernickes Korsakoffs

Question 44

Coenzyme of thiamine is

Answer 44

Thiamine Pyrophosphate TPP

Question 45

Broad beans common in Mediterranean diets Presents as pallor, hemoglobinuria, jaundice and severe anemia 24-48h after ingestion of beans

Answer 45

Favism

Question 46

Caused by genetic deficiency of NADPH oxidase in WBCs

Answer 46

Chronic Granulomatous Disease

Question 47

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

Answer 47

Chronic granulomatous disease

Question 48

CGD is confirmed by

Answer 48

Negative nitroblue tetrazolium test

Question 49

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

Answer 49

Transketolase

Question 50

Conversion of malonyl coA to Fatty acid requires

Answer 50

NADPH

Question 51

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

Answer 51

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

Question 52

Ribulose 5 Phosphate is converted to Xylulose 5 phosphate by

Answer 52

Ribulose-phosphate-3-epimerase Xylulose-5-phosphate can be shunted to Fructose-6-phosphate and proceed Glycolysis

Question 53

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

Answer 53

5-phosphoribosyl-1-pyrophosphate | PRPP

Question 54

G6PD Deficiency manifests clinically as

Answer 54

Hemolytic anemia Neonatal hyperbilirubinemia After eating fava beans and drugs inducing hemolysis

Question 55

Glucose 6 Phosphate Dehydrogenase is stimulated by

Answer 55

Insulin | NADP

Question 56

Glucose 6 Phosphate Dehydrogenase is inhibited by

Answer 56

NADPH

Question 57

Enzyme requires thiamine B1 needed for interconversions Only thiamine enzyme in RBC

Answer 57

Transketolase

Question 58

HMP is particularly important in these organs

Answer 58

``` Liver Mammary glands (FA synthesis) Adrenal cortex (NADPH dependent synthesis of steroids) ```

Question 59

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

Answer 59

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

Question 60

Gamma glutamyl cysteinyl glycine Tripeptide thiol Detoxifies hydrogen peroxide via glutathione peroxidase

Answer 60

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

Question 61

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

Answer 61

Respiratory burst Neurrophil phagocytosis and oxygen dependent myeloperoxidase system for killing bacteria

Question 62

Oxidant drugs

Answer 62

Antibiotics (sulfamethoxazole) Antimalarials Antipyreric (Acetanilid only)

Question 63

Most commmon precipitating factor of hemolysis in G6PD

Answer 63

Infection

Question 64

Mutations causing the nonspherocytic hemolytic anemia occur are clustered in the

Answer 64

carboxyl end G6PD Mediterranean Class I Severe

Question 65

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

Answer 65

amino end G6PD Class III A (prototype)

Question 66

Severe hyperuricemia or gout is caused by deficiency these enzymes

Answer 66

Glucose-6-phosphatase | Hypoxanthine-guanine-phosphoribosyltransferase HGPRT

Question 67

Severe hyperuricemia or gout is caused by elevated activity of this

Answer 67

5-phosphoribosyl-pyrophosphate synthetase PRPP