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USMLE Biochemistry > HMP Shunt > Flashcards

HMP Shunt Flashcards

1
Q

What are other names dor the HMP shunt?

A
  • Hexose monophosphate shunt
  • Pentose phosphate pathway
  • 6-phosphogluconate pathway
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2
Q

Why is it called a ‘shunt’?

A

Glucose-6-phosphate ‘shunted’ away from glycolysis

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3
Q

What does the HMP shunt synthesise?

A
  • NADPH (many uses)

- Ribose-5-phosphate (nucleotide synthesis)

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4
Q

What 2 diseases may affect the HMP shunt?

A
  • G6PD deficiency

- Thiamine deficiency (transketolase)

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5
Q

Where does the HMP shunt occur?

A

Cytosol

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6
Q

What are the 2 phases of the HMP shunt?

A
  • Oxidative: irreversible, rate-limiting

- Reductive: reversible

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7
Q

What are the reaction in the oxidative phase of the HMP shunt?

A

G6P
(NADP+ -> NADPH)
-> 6 phosphogluconate (NADP+ -> NADPH)
-> Ribulose-5 Phosphate (+CO2)

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8
Q

What enzyme catalyses the reaction of G6P to 6 phosphogluconate?

A

Glucose-6 Phosphate Dehydrogenase

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9
Q

What can ribulose-5-Phosphate be converted via to then be converted to Fructose-6-phosphate?

A

Ribose-5 Phosphate

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10
Q

What enzyme catalyses the reaction of Ribose-5 Phosphate to F6P?

A

Transketolase (transfers a Carbon unit)

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11
Q

What vitamin is required a s a co-factor for transkelotase?

A

Thiamine (B1)

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12
Q

What may pre-dispose to Wernicke-Korsakoff syndrome, outside of alcoholics?

A

Abnormal transkelotase enzyme -> abnormal binding to thiamine

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13
Q

What are the uses of NADPH?

A
  • Cofactor in fatty acid, steroid synthesis
  • Phagocytosis
  • Protection from oxidative damage (RBCs)
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14
Q

What do phagocytes generate to perform oxygen dependent killing?

A

H2O2

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15
Q

What is involved in oxygen independent killing?

A
  • Low pH

- Enzymes

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16
Q

What enzymes are involved in the production of H2O2?

A
  • NADPH oxidase
  • Superoxide dismutase
  • Myeloperoxidase
17
Q

What are the molecules involved in respiratory burst?

A 
O2
NADPH Oxidase (NADPH -> NADP+)
-> O2-
Superoxide Dismutase
-> H2O2 (+Cl-)
Myeloperoxidase
-> HOCl
18
Q

What enzyme converts O2 to O2-?

A

NADPH Oxidase

19
Q

What enzyme converts O2- to H2O2?

A

Superoxide dismutase

20
Q

What ion is added and enzyme converts to H2O2 to create Hypochlorus acid (bleach)?

A

Myeloperoxidase + Cl-

21
Q

What enzyme is defective in Chronic Granulomatous Disease?

A

NADPH Oxidase (involved in first step of resp burst)

O2 -> O2-

22
Q

What are CGD patients at risk of?

A

Catalse + bacteria

  • Staph aureus
  • Pseudomonas
  • Serratia
  • Nocardia
  • Aspergillus
23
Q

What 5 organisms are CGD patients most at risk of?

A
  • Staph aureus
  • Pseudomonas
  • Serratia
  • Nocardia
  • Aspergillus
24
Q

How does G6PD deficiency cause RBC issues?

A

Less NADPH produced From HMP shunt reactions (NAD+ ->NADPH)

  • NADPH required to break down H2O2
  • Hemolysis
25
What substances can lead to worsening G6PD deficiency (H2O2 generation)?
- Infection (macrophages generate free radicals) - Fava beans (oxidants) - Antibioics (sulfa drugs, dapsone, nitrofurantoin, INH) - Primaquine, quinidine - Aspirin and acetaminophin (rarely)
26
What is H2O2 converted into in the presence of glutathione?
H2O and Glutathione Disulfide | - Enzyme: Glutathione Peroxidase
27
What substance is required to convert H2O2 into H2O and Glutathione disulfide?
Glutathione
28
What Substance is required in order to produce Glutathione from glutathione disulfide?
NADPH | - (+ H+) (from the HMP shunt, requires G6PD)
29
Why are those with G6PD deficiecny unable to break down H2O2?
They do not have enough NADPH therefore cannot get enough Glutathione (from Glutathione disulfide) - Glutathione required to convert H2O2 into H2O and Glutathione disulfide
30
Why are those with G6PD deficiecny unable to break down H2O2?
They do not have enough NADPH therefore cannot get enough Glutathione (from Glutathione disulfide) - Glutathione required to convert H2O2 into H2O and Glutathione disulfide
31
How is G6PD deficiency inherited?
X-linked recessive
32
How may G6PD deficiency present?
Recurrent hemolysis after trigger | - May present w. dark urine
33
What are Heinz bodies?
Oxidised Hgb precipitated in RBCs (blue dots)
34
What are bite cells due to?
Phagocytic removal by splenic macrophages
35
How is G6PD deficiency diagnosed?
- Fluorescent spot test - Detects generation of NADPH from NADP - Positve test if blood spot fails to fluoresce under UV light
36
How is G6PD deficiency treated?
Avoidance of triggers

USMLE Biochemistry (44 decks)

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