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USMLE Biochemistry > HMP Shunt > Flashcards

HMP Shunt Flashcards

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USMLE® Step 1 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
Q

What substances can lead to worsening G6PD deficiency (H2O2 generation)?

A
  • Infection (macrophages generate free radicals)
  • Fava beans (oxidants)
  • Antibioics (sulfa drugs, dapsone, nitrofurantoin, INH)
  • Primaquine, quinidine
  • Aspirin and acetaminophin (rarely)
26
Q

What is H2O2 converted into in the presence of glutathione?

A

H2O and Glutathione Disulfide

- Enzyme: Glutathione Peroxidase

27
Q

What substance is required to convert H2O2 into H2O and Glutathione disulfide?

A

Glutathione

28
Q

What Substance is required in order to produce Glutathione from glutathione disulfide?

A

NADPH

- (+ H+) (from the HMP shunt, requires G6PD)

29
Q

Why are those with G6PD deficiecny unable to break down H2O2?

A

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
Q

Why are those with G6PD deficiecny unable to break down H2O2?

A

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
Q

How is G6PD deficiency inherited?

A

X-linked recessive

32
Q

How may G6PD deficiency present?

A

Recurrent hemolysis after trigger

- May present w. dark urine

33
Q

What are Heinz bodies?

A

Oxidised Hgb precipitated in RBCs (blue dots)

34
Q

What are bite cells due to?

A

Phagocytic removal by splenic macrophages

35
Q

How is G6PD deficiency diagnosed?

A
  • Fluorescent spot test
  • Detects generation of NADPH from NADP
  • Positve test if blood spot fails to fluoresce under UV light
36
Q

How is G6PD deficiency treated?

A

Avoidance of triggers

USMLE Biochemistry (44 decks)

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