Eicosanoids: Major Classes and Effects

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Questions and Answers

Which eicosanoid class is primarily involved in the inhibition of platelet aggregation?

Thromboxanes

Prostacyclins (correct)

Leukotrienes

Prostaglandins

What symptom is NOT typically associated with eicosanoid effects?

Mediation of pain signals

Induction of fever

Smooth muscle contraction

Stimulation of neural tissue regeneration (correct)

In the clinical profile of John Smith, elevated plasma levels of which eicosanoid contributed to inflammation?

Thromboxane A2 (TXA2)

HETE (Hydroxyeicosatetraenoic acid)

Prostacyclin I2 (PGI2)

Prostaglandin E2 (PGE2) (correct)

How might increasing omega-3 fatty acids, such as fish oil, impact inflammation?

Modulate eicosanoid pathways towards lower inflammation Signup and view all the answers

What role do leukotrienes primarily play in the body?

Induction of inflammation and bronchoconstriction Signup and view all the answers

Which treatment option is commonly used for rapid reduction of inflammation in cases of elevated eicosanoids?

Corticosteroids Signup and view all the answers

Which of the following is NOT a known effect of eicosanoids?

Protection against free radical damage Signup and view all the answers

What is a common characteristic of thromboxanes?

Stimulate platelet aggregation Signup and view all the answers

Which statement best describes HETEs?

They are derived from arachidonic acid. Signup and view all the answers

What clinical feature might suggest the need for stronger NSAIDs in John's treatment plan?

Minimal relief from over-the-counter NSAIDs Signup and view all the answers

What characterizes chronic hormone secretion?

Relatively constant concentration of hormone Signup and view all the answers

How is down-regulation of receptors defined?

Decreases in the synthesis of receptors following prolonged hormonal exposure Signup and view all the answers

Which process describes an increase in sensitivity to a hormone?

Up-regulation Signup and view all the answers

Where are receptors for protein or peptide hormones located?

On the plasma membrane Signup and view all the answers

What role do trans-membrane domains play in receptor function?

They span the cell membrane to anchor the receptor Signup and view all the answers

What is a common consequence of prolonged hormone exposure on receptors?

Increased degradation of receptor molecules Signup and view all the answers

Which domain of a receptor interacts with hormones?

Ligand-binding domains Signup and view all the answers

What primarily explains the phenomenon of desensitization to some drugs?

Prolonged exposure leading to down-regulation of receptors Signup and view all the answers

Which hormone can cause an increase in LH receptors in the ovary?

FSH Signup and view all the answers

What type of hormone secretion occurs in reaction to a specific stimulus?

Acute hormone secretion Signup and view all the answers

What is the primary reason peptide or protein hormones can dissolve easily in plasma?

They possess high water solubility due to their structure. Signup and view all the answers

Which statement correctly describes steroid hormone transport in the bloodstream?

The majority of steroid hormones are transported bound to proteins. Signup and view all the answers

What role do specialized binding proteins play in hormone transport?

They possess high affinity but low capacity for hormone binding. Signup and view all the answers

What happens to hormone action due to its binding to proteins?

Binding allows the hormone action to be prolonged. Signup and view all the answers

Which of the following explains why only free hormones are biologically active?

Only free hormones can effectively bind to receptors. Signup and view all the answers

What is the typical concentration range of Insulin in the blood?

$10^{-12}M$ to $10^{-11}M$ Signup and view all the answers

Why is aldosterone considered an exception in steroid hormone concentration?

It is present in significantly lower concentrations than other steroids. Signup and view all the answers

Which binding protein is specifically mentioned for binding cortisol?

Cortisol Binding Globulin (CBG) Signup and view all the answers

Which of the following is not a consequence of hormone binding?

Increases hormone levels through synthesis. Signup and view all the answers

What is the main function of non-specialized binding proteins in hormone transport?

They act as a reservoir for hormones due to their high capacity. Signup and view all the answers

What is the initial action of Ga when the signal is turned off?

It hydrolyzes GTP to GDP + Pi. Signup and view all the answers

What is the effect of the presence of GDP on Ga?

It rebinds to the inhibitory bg complex. Signup and view all the answers

Which enzyme is responsible for hydrolyzing cAMP to AMP?

Phosphodiesterase. Signup and view all the answers

Receptor tyrosine kinases are primarily involved in signaling for which of the following?

Insulin and growth factors. Signup and view all the answers

What type of receptor is associated with thyroid hormone action?

Nuclear receptors. Signup and view all the answers

What role does adenylate cyclase have in the cAMP signaling pathway?

It synthesizes cAMP from ATP. Signup and view all the answers

Which of the following correctly describes the action of phosphodiesterases?

They degrade cAMP to AMP. Signup and view all the answers

Which statement is true regarding the signal amplification process?

It involves multiple steps of activations. Signup and view all the answers

What is the consequence of adenylate cyclase being inactivated by GDP-bound Ga?

Decrease in cAMP production. Signup and view all the answers

What is a characteristic of trans-membrane receptors with intrinsic tyrosine kinase activity?

They involve phosphorylation of tyrosine residues. Signup and view all the answers

Study Notes

Major Classes of Eicosanoids

Prostaglandins
Thromboxanes
Prostacyclins
Leukotrienes
HETEs

Synthesis of Eicosanoids

Diacylglycerol or phospholipid is the starting material
Arachidonic acid is released from the phospholipid
Prostaglandin H2 (PGH2) is a key intermediate
Different enzymes are responsible for converting PGH2 to other eicosanoids (e.g., prostaglandin D2, E2, F2α, etc.)
Lipoxygenase enzymes are involved in leukotriene synthesis
Thromboxanes are produced from PGH2.
Prostacyclins are produced from PGH2.

Effects of Eicosanoids

Induce inflammation
Mediate pain signals
Induce fever
Cause smooth muscle contraction (e.g., uterus)
Promote smooth muscle relaxation
Protect the stomach lining
Stimulate platelet aggregation
Inhibit platelet aggregation
Cause sodium and water retention

Clinical Relevance

Elevated eicosanoids contribute to inflammation and pain
NSAIDs, corticosteroids, disease-modifying antirheumatic drugs (DMARDs) , and lifestyle modifications such as increasing omega-3 fatty acid intake are treatment considerations

Synthesis of Hormone Derivatives of Tryptophan

L-Tryptophan is the precursor
Tryptophan-5-hydroxylase converts L-tryptophan to 5-hydroxytryptophan
5-Hydroxytryptophan decarboxylase converts 5-hydroxytryptophan to serotonin
Serotonin N-acetyltransferase (NAT) converts serotonin to N-acetylserotonin
Hydroxindole-0-methyltransferase converts N-acetylserotonin to melatonin

Synthesis of Hormone Derivatives of Tyrosine

Tyrosine is the starting material
Tyrosine hydroxylase (TH) converts tyrosine to DOPA
DOPA decarboxylase (DDC) converts DOPA to dopamine
Dopamine β-hydroxylase (DBH) converts dopamine to norepinephrine
Phenylethanolamine-N-methyltransferase (PNMT) converts norepinephrine to epinephrine

Synthesis of Thyroid Hormones

Tyrosine is the precursor for thyroid hormones
Iodination of tyrosine residues within the protein thyroglobulin results in the formation of T4 and T3.
Thyroid hormones are produced in the thyroid gland.

Transport of Hormones

Peptide/protein hormones dissolve easily in plasma, but are still carried bound to carrier proteins
Steroid/amine hormones are relatively insoluble in plasma, and mostly transported bound to proteins

Binding Proteins

Specialized binding proteins have high affinity (strong binding), but low capacity for binding
Non-specialized binding proteins have low affinity, but high capacity for binding

Consequences of Binding

Prevents hormones from overacting by keeping them bound to carrier proteins
Prolongs the effect of hormones by preventing rapid inactivation and excretion
Prevents large fluctuations in active hormone levels
Increased reservoir of hormone

Hormone Concentration in Blood

Peptide hormones generally have low concentrations in the blood.
Steroid hormones tend to have much higher levels in the blood, often with some exceptions

Patterns of Hormone Secretion

Chronic hormone secretion maintains relatively constant levels over time.
Acute hormone secretion responds rapidly to stimuli (often minutes or hours)
Episodic/cyclic hormone secretion shows fluctuations and patterns.

Hormone Specificity

Hormones only affect target tissues with specific receptors.
Receptor numbers are not constant; they are continually degraded and replaced.
Downregulation can occur due to prolonged hormone exposure, where the synthesis rate of receptors decreases and the rate at which they are degraded increases.
Upregulation occurs if the synthesis of receptors increases due to hormone exposure.

Receptor Location

Protein/peptide hormones cannot pass through the plasma membrane.
Receptors are located on the plasma membrane.
The structure of these receptors features extracellular, transmembrane, and cytoplasmic/intracellular domains.

cAMP Second Messenger System

Hormones initiate signaling cascades via 2nd messengers such as cAMP.
cAMP is generated from ATP by adenylate cyclase, and activates protein kinase.
Protein kinase regulates several cellular responses.

Turning Off the Signal

Ga hydrolyzes GTP to GDP, causing disassociation from adenylate cyclase, and inhibiting its activity.
Phosphodiesterases catalyse hydrolysis of cAMP to AMP, thus terminating the signaling cascade.

Various Cellular Responses from cAMP

Many cellular responses are triggered by cAMP, such as secretion, enzyme activation or inhibition, lipid breakdown, glycogen synthesis, glycogen breakdown, protein synthesis, differentiation, DNA synthesis, and Ca2+ transport

Amplification

Hormone signaling is amplified at various stages within a cell.

Other Protein Hormone Receptors

Transmembrane receptors with intrinsic tyrosine kinase activity are receptors for insulin and many growth factors.
These receptors possess an intracellular domain, which contains an intrinsic tyrosine kinase activity.

Steroid Hormone Action

Steroid hormones can pass through cell membranes directly and bind to receptors in the cytoplasm or nucleus.
The hormone-receptor complex alters gene expression, leading to the synthesis of new proteins.
This mechanism often produces a slow but more sustained cellular response.

Thyroid Hormone Nuclear Receptor

Thyroid hormone (T3 and T4) binds to nuclear receptors, initiating a cascade that results in the synthesis of specific proteins.
The mechanism directly affects gene expression.

Hormones Acting Via cAMP

Specific hormones activate cAMP signaling pathways.

Hormones Acting Via cGMP

Certain hormones utilize cGMP as a second messenger.

Hormones Acting Via Tyrosine Kinase/Phosphatase Cascade

Certain hormones trigger downstream signaling through a tyrosine kinase/phosphatase cascade.

Hormone Second Messenger System

Phospholipase C (PLC) pathway generates IP3 and DAG, which activates protein kinase C (PKC).
These components regulate calcium fluxes, leading to varied cellular responses.

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Description

Explore the major classes of eicosanoids, including prostaglandins, thromboxanes, and leukotrienes. This quiz covers their synthesis, physiological effects, and clinical relevance, particularly in relation to inflammation and pain management. Test your knowledge and understanding of this important biochemical topic.