Biochemistry of Arachidonic Acid

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Questions and Answers

What is the chemical name for arachidonic acid?

8,11,14-eicosatrienoic acid

5, 8, 11, 14-eicosatetraenoic acid (correct)

Hexadecanoic acid

6,9-eicosadienoic acid

Where in the cell does arachidonic acid primarily originate?

Mitochondria

Plasma membrane (correct)

Endoplasmic reticulum

Nucleus

What physiological stimuli can lead to the release of arachidonic acid from the plasma membrane?

Skeletal muscle contraction

Norepinephrine (correct)

Increased oxygen levels

Hypoglycemia

Which enzyme is activated in response to various stimuli, leading to the cleavage of arachidonic acid from membrane phospholipids?

Phospholipase A2 (PLA2) Signup and view all the answers

Which condition is primarily associated with the use of NSAIDs?

Hyperkalemia Signup and view all the answers

What are the two primary biochemical pathways arachidonic acid can enter?

COX and LOX pathways Signup and view all the answers

What is a consequence of aspirin's irreversible inhibition of COX-1?

Potential respiratory alkalosis Signup and view all the answers

Which of the following drugs may have decreased clearance due to NSAID therapy?

Lithium Signup and view all the answers

What role does COX-1 play in physiological functions?

Acts as a housekeeping enzyme Signup and view all the answers

Why is aspirin considered an irreversible inhibitor of COX enzymes?

It modifies the enzyme permanently Signup and view all the answers

What dosage of aspirin is indicated for the primary prevention of myocardial infarction?

81 mg PO daily Signup and view all the answers

What is the primary result when arachidonic acid interacts with COX enzymes?

Generation of prostaglandin G2 (PGG2) Signup and view all the answers

What is the primary acid-base disturbance caused by salicylic acid in aspirin therapy?

Respiratory alkalosis Signup and view all the answers

What unstable molecule is formed when arachidonic acid interacts with 5-LOX?

5-HPETE Signup and view all the answers

What is the end product when LTA4 interacts with LTA4 hydrolase?

LTB4 Signup and view all the answers

Which of the following leukotrienes contains cysteine?

LTC4 Signup and view all the answers

Which characteristic is NOT a defining feature of NSAID clinical necessity?

Clinical efficacy in pain relief Signup and view all the answers

What is the mechanism by which inhibition of COX-1 leads to gastric toxicity?

Decreased PGE1 levels Signup and view all the answers

Which class of NSAIDs is more likely to lead to gastric injury?

Cox-1 inhibitors Signup and view all the answers

What effect do NSAIDs have on renal function by inhibiting COX?

Decrease GFR Signup and view all the answers

What is the characteristic of most NSAIDs that contributes to gastric toxicity?

They are weak acids Signup and view all the answers

Which NSAID is highly selective for COX-2 and suitable for long-term treatment of chronic pain?

Celecoxib Signup and view all the answers

What is a significant concern related to the first-pass metabolism of diclofenac?

Low bioavailability Signup and view all the answers

Which NSAID is an extremely potent COX-1 inhibitor often used in neonates for PDA closure?

Indomethacin Signup and view all the answers

Which characteristic of ibuprofen makes it suitable for acute pain management?

Short half-life Signup and view all the answers

What is the effect of a lower IC50 value on an NSAID?

Higher potency in inhibition Signup and view all the answers

Which NSAID should be used with caution due to the risk of Steven-Johnson Syndrome (SJS) when combined with certain medications?

Meloxicam Signup and view all the answers

Nabumetone is activated to which compound in the liver?

6-MNA Signup and view all the answers

Which NSAID has a longer half-life allowing it to be used for chronic pain management?

Naproxen Signup and view all the answers

Study Notes

Arachidonic Acid

Arachidonic acid's chemical name is 5, 8, 11, 14-eicosatetraenoic acid.
The numbers 5, 8, 11, and 14 correspond to the locations of double bonds within the molecule.
Eicosa refers to 20 carbons.
Arachidonic acid originates in the plasma membrane from lipid portions.

Physiologic Stimuli

Physiologic stimuli trigger the release of arachidonic acid from the plasma membrane.
These stimuli include vascular injury, inflammation (acute or chronic), norepinephrine, and infection.

Biochemical Steps

Physiologic stimuli activate phospholipase A2 (PLA2).
Calcium is required for PLA2 activation.
PLA2 cleaves arachidonic acid from membrane phospholipids.

Biochemical Pathways

Arachidonic acid can enter two biochemical pathways:
- Cyclooxygenase (COX) pathway.
- Lipoxygenase (LOX) pathway.

COX Pathway

Arachidonic acid interacts with cyclooxygenase (COX).
This interaction forms an unstable intermediate called prostaglandin G2 (PGG2).
PGG2 reacts with COX to form prostaglandin H2 (PGH2).
PGH2 is a more stable product.

COX-1 and COX-2

Two COX isoforms exist.
COX-1 is a "housekeeping" enzyme, constantly active, and involved in protective functions like gastric protection.
Increased bicarbonate production in the stomach results from the activation of PGE1.
COX-2 is inducible—expressed only in response to tissue damage or infection.

LOX Pathway

5-LOX is a key enzyme.
Arachidonic acid reacts with 5-LOX
Products include LTA4, LTB4, LTC4, LTD4, and LTE4.
These are known as cysteinyl leukotrienes; they generally contain cysteine amino acid.

Defining Characteristics of NSAIDs

Renal function
Gastrointestinal integrity
Pharmacokinetics (half-life, bioavailability)
Plasma protein binding (albumin)
Drug-drug interactions (especially with cytochrome P450 enzymes)
Elimination (hepatic function)

Gastric Toxicity

COX-1 inhibition decreases PGE1 production.
Decreased PGE1 leads to decreased mucus production and decreased bicarbonate intravasation.

Renal Toxicity

NSAIDs can inhibit COX, decreasing prostacyclin (PGI2) production.
Decreased vasodilation, increased vasoconstriction of afferent and efferent renal arterioles occurs.
Reduced glomerular filtration rate (GFR) occurs.

Other Drug Interactions

NSAIDs can affect the clearance of other drugs (e.g., lithium).
Some NSAIDs lower potassium excretion, increasing serum potassium levels (hyperkalemia).

NSAID Indications

Primarily used for pain relief (analgesia).
Can be used to prevent myocardial infarction (MI) and stroke.

Respiratory Alkalosis

Aspirin can cause respiratory alkalosis.
Salicylic acid is acidic.
The brain increases respiratory rate, leading to CO2 expiration.
Reduced CO2 in the bloodstream increases blood pH, causing respiratory alkalosis.

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Description

Explore the chemical properties and physiological implications of arachidonic acid. This quiz covers its biochemical pathways, the role of phospholipase A2, and the significance of various stimuli in its release. Test your understanding of the COX and LOX pathways as well as their impact on health.