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BIOCHEMISTRY II > WEEK 4 (HMP Shunt) > Flashcards

WEEK 4 (HMP Shunt) Flashcards

1
Q

What is the HMP shunt also known as?

A

Pentose phosphate pathway

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2
Q

In which molecule in Glycolysis does the reaction shunt away?

A

Glucose-6-Phosphate

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3
Q

What are the key things to remember about the HMP shunt?

A
  • Occurs in the cytoplasm
  • Main organs are LIVER, MAMMARY GLANDS, RBCs & ADRENAL CORTEX
  • Goal is to produce NADPH
  • 2 phases: Oxidative (irreversible, rate-limiting) & Reductive (reversible)
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4
Q

What does the HMP shunt synthesise?

A
  • 2 molecules of NADPH
  • Ribose-5-Phosphate
  • CO2
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5
Q

Why is NADPH needed?

A
  • Glutathione reduction (Free radical detoxification)
  • Fatty acid synthesis
  • Steroid hormone synthesis
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6
Q

Which organs use the HMP shunt to synthesis fatty acids?

A
  • Liver
  • Lactating mammary glands
  • Adipose tissue
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7
Q

Which organs use the HMP shunt to synthesis Steroid hormones?

A
  • Testes
  • Ovaries
  • Placenta
  • Adrenal cortex
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8
Q

What requires NADPH to keep glutathione reduced?

A

RBCs

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9
Q

What are the irreversible oxidative reactions?

A

3 reactions that lead to formation of ribulose-5-phosphate, CO2 & 2 molecules of NADPH

Glucose-6-phosphate -> 6-Phosphoglucanolactone -> 6-Phosphogluconate -> Ribulose-5-phosphate

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10
Q

What is the enzyme that converts Glucose-6-Phosphate to 6-Phosphoglucanolactone?

A

Glucose-6-Phosphate Dehydrogenase

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11
Q

What is the enzyme that converts 6-Phosphoglucanolactone to 6-Phosphogluconate?

A

Glucanolactone Hydrolase

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12
Q

What is the enzyme that converts 6-Phosphogluconate to Ribulose-5-Phosphate?

A

6-Phosphogluconate Dehydrogenase

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13
Q

What are the Reversible non-oxidative reactions?

A

Reversible reactions that permit Ribulose-5-Phosphate to be converted to either RIBOSE-5-PHOSPHATE (needed for nucleotide synthesis) or to INTERMEDIATES OF GLYCOLYSIS (Fructose-6-Phosphate & Glyceraldehyde-3-Phosphate)

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14
Q

What are the properties of Transketolase?

A
  • Transfers a carbon unit to create Fructose-6-Phosphate
  • Requires thiamine (B1) as a co-factor
  • Associated with WERNICKE-KORSAKOFF SYNDROME (memory disorder that results from vitamin B1 deficiency and is associated with alcoholism)
  • Abnormal transketolase may predispose
  • Affected individuals may have abnormal binding to thiamine
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15
Q

What are the uses of Hydrogen peroxide reduction?

A
  • Co-factor in fatty acid & steroid synthesis
  • Protection from oxidative damage
  • Phagocytosis
  • Used in “reductive” reactions (releases hydrogen to form NADP+)
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16
Q

How are Reactive Oxygen Species (ROS) formed?

A
  • Continuously as by-products of aerobic metabolism
  • Through reactions with drugs & environmental toxins
  • When the level of antioxidants is diminished

All creating conditions of OXIDATIVE STRESS

17
Q

What can highly reactive oxygen intermediates cause?

A

Serious chemical damage to DNA, Proteins and can lead to cell death

18
Q

What is the function of Reduced Glutathione (G-SH)?

A

Reduced Glutathione (G-SH) can chemically detoxify H2O2 why by GLUTATHIONE PEROXIDASE forms OXIDISED GLUTATHIONE (G-S-S-G) which no longer has protective properties

19
Q

How does the cell regenerate Reduced Glutathione (G-SH)?

A

In a reaction catalysed by GLUTATHIONE REDUCTASE using NADPH as a source of reducing equivalents. Additional enzymes (e.g SUPEROXIDE DISMUTASE & CATALASE) catalyse the conversion of other ROS (Reactive oxygen species) to harmless products.

20
Q

What is able to reduce and detoxify ROS in the lab?

A

Antioxidant chemicals & a number of intracellular reducing agents

(e.g ASCORBATE, VITAMIN E & B-CAROTENE)

21
Q

What is Phagocytosis and what are its properties?

A

PHAGOCYTOSIS = Ingestion by receptor-mediated endocytosis of microorganisms, foreign particles & cellular debris

  • Neutrophils & Macrophages
  • Generate H2O2 to kill bacteria
22
Q

What are the 2 mechanisms of Phagocytosis?

A
  • OXYGEN-INDEPENDENT KILLING (uses pH changes in PHAGOLYSOSOMES & LYSOSOMAL ENZYMES to destroy pathogens)
  • OXYGEN-DEPENDENT SYSTEM (uses NADPH OXIDASE, SUPEROXIDE DISMUTASE & MYELOPEROXIDASE)
23
Q

Describe CGD-Chronic Granulomatous Disease

A
  • Loss of function of NADPH oxidase
  • Phagocytes cannot generate H2O2
  • Phagocytes use despite enzyme deficiency
  • Catalase (-) bacteria generate their own H2O2
  • Catalyse (+) bacteria breakdown H2O2 -> Host cells have no H2O2 to use -> Recurrent infections
24
Q

Which 5 organisms cause almost all CGD infections?

A
  • Staph aureus
  • Pseudomonas
  • Serratia
  • Nocardia
  • Aspergillus
25
Q

What are the properties of Nitric Oxide?

A
  • Mediator
  • Endothelium-derived relaxing factor that causes vasodilation by relaxing vascular smooth muscle
  • Neurotransmitter -> Prevents platelet aggregation -> Plays an essential role in macrophage function
26
Q

What are the properties of Nitric Oxide synthesis?

A
  • 3 NOS isozymes
  • 2 are CONSTITUTIVE, CALCIUM-CALMODULIN-DEPENDENT enzymes that are found primarily in ENDOTHELIUM & NEURAL TISSUE and constantly produce very low levels of NO for vasodilation and neurotransmission
  • INDUCIBLE, CA2+ INDEPENDENT ENZYME can be expressed in many cells as an early defence against pathogens
27
Q

Describe the physiology behind Glucose-6-Phosphate

A

NADPH is necessary to keep GLUTATHIONE reduced which detoxifies free radicals and peroxides -> Decrease in NADPH in RBCs leads to HEMOLYTIC ANEMIA due to poor RBC defines against oxidising agents -> Infection can cause HEMOLYSIS -> Inflammatory response produces FREE RADICALS that diffuse into RBCs -> Oxidative damage

28
Q

What are the properties of Glucose-6-Phosphate Dehydrogenase deficiency?

A
  • X-linked recessive disorder
  • Most common human enzyme deficiency
  • Increased malarial resistance
  • HEINZ BODIES (oxidised haemoglobin precipitated in RBCs)
  • BITE CELLs (Result from the Phagocytic removal of Heinz bodies by splenic macrophages)

BIOCHEMISTRY II (12 decks)

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