Prostaglandins?

Question 1

What are eicosanoids?

Answer 1

Eicosanoids are signaling molecules derived from fatty acids, primarily arachidonic acid. They play crucial roles in inflammation, immunity, and various physiological processes in the body. Eicosanoids include prostaglandins, thromboxanes, and leukotrienes.

Question 2

Eicosanoids are a derivative of a hypothetical ______ carbon fatty acid?

Answer 2

20 carbons (prostanoic acid)

Question 3

Which compounds inhibit prostaglandin synthesis and why?

Answer 3

Corticosteroids
Ibuprofen (as prostaglandins induce pain and ibuprofen is used as a pain killer)
and aspirin

Corticosteroids and aspirin inhibit prostaglandin secretion through different mechanisms:

1. Corticosteroids: These are synthetic drugs that mimic the action of cortisol, a hormone naturally produced by the adrenal glands. Corticosteroids exert their anti-inflammatory effects by inhibiting the activity of phospholipase A2, an enzyme involved in the release of arachidonic acid from cell membranes.(From membrane bound phospholipids)
   By blocking this enzyme, corticosteroids reduce the availability of arachidonic acid, the precursor of prostaglandins. As a result, the synthesis of prostaglandins is inhibited, leading to decreased inflammation and immune responses.
2. Aspirin: Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits the activity of cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. These enzymes are involved in the conversion of arachidonic acid into prostaglandins. Aspirin irreversibly acetylates a serine residue in the active site of COX enzymes, leading to their inhibition. By blocking COX activity, aspirin prevents the formation of prostaglandins, thereby reducing inflammation, pain, and fever.

Both corticosteroids and aspirin ultimately inhibit prostaglandin secretion by interfering with the enzymatic pathways responsible for prostaglandin synthesis.

Question 4

Explain the types of eicosanoids?

Answer 4

Certainly! Eicosanoids can be broadly categorized into three main types:

1. Prostaglandins: These are lipid compounds derived from arachidonic acid metabolism. Prostaglandins are involved in inflammation, regulation of blood flow, gastrointestinal function, and other physiological processes. They are produced by most cells in the body and act locally, exerting diverse effects.
2. Thromboxanes: Thromboxanes are also derived from arachidonic acid and are primarily known for their role in blood clotting and vasoconstriction. They are produced by **platelets*” and contribute to the formation of blood clots at sites of injury, promoting hemostasis.
3. Leukotrienes: These are another group of eicosanoids derived from arachidonic acid, primarily synthesized by white blood cells (leukocytes). Leukotrienes are involved in inflammation, allergic reactions, and asthma. They promote the recruitment and activation of immune cells, contributing to the body’s defense mechanisms.

Each type of eicosanoid plays a distinct role in regulating various physiological processes and maintaining homeostasis in the body.

Question 5

Which eicosonaids promote and which inhibit platelet aggregation?

Answer 5

Promotes:
Thromboxane A2
Prostaglandin E1

Inhibits:
Prostacyclibs PGI2

Question 6

O

Question 7

What is salvage pathway?

Answer 7

The salvage pathway is a cellular process that involves the recycling of nucleotide bases, nucleosides, or nucleotides from degraded nucleic acids or from external sources, such as dietary intake. Instead of synthesizing these components from scratch, the salvage pathway conserves energy by reusing and converting existing nucleic acid components into nucleotides through enzymatic reactions. This pathway helps maintain adequate levels of nucleotides for DNA and RNA synthesis and other cellular processes, contributing to cellular homeostasis and efficient resource utilization.

Question 8

Steps of salvage pathway of pyrine synthesis?

Answer 8

The salvage pathway of purine synthesis involves several steps to recycle purine bases, nucleosides, or nucleotides. Here are the general steps involved:

1. Nucleoside phosphorylation: Purine nucleosides (such as adenosine and guanosine) obtained from degradation or external sources are phosphorylated by specific kinases to form nucleotides. For example, adenosine is converted to adenosine monophosphate (AMP) by adenosine kinase.
2. Nucleotide interconversion: In some cases, nucleoside monophosphates obtained from the salvage pathway can be converted into other nucleotides through interconversion reactions. For instance, adenosine monophosphate (AMP) can be converted into guanosine monophosphate (GMP) through a series of enzymatic reactions.
3. Nucleotide salvage: In cases where purine bases are available, they can be directly salvaged to form nucleotides. For example, hypoxanthine and guanine can be converted into inosine monophosphate (IMP) and guanosine monophosphate (GMP), respectively, through the action of specific salvage enzymes.
4. Phosphorylation: Nucleotides formed through the salvage pathway may undergo further phosphorylation to generate diphosphate (DP) or triphosphate (TP) forms, depending on the cellular requirements. These phosphorylation reactions are catalyzed by nucleotide kinases.

Overall, the salvage pathway of purine synthesis efficiently recycles purine bases and nucleosides to generate nucleotides, thereby conserving energy and resources for cellular processes.

Question 9

Explain Lesh Nyhan syndrome?

Answer 9

Lesch-Nyhan syndrome (LNS) is a rare genetic disorder characterized by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This enzyme is involved in the salvage pathway of purine metabolism, which recycles purine bases to form nucleotides.

The deficiency of HPRT leads to the accumulation of uric acid and the decreased production of guanine and hypoxanthine nucleotides. This results in a range of neurological and behavioral symptoms, including:

1. Severe motor dysfunction: Individuals with LNS often exhibit profound neurological impairment, including dystonia, spasticity, and choreoathetosis. These movement disorders can be severe and debilitating.
2. Self-injurious behavior: One of the hallmark features of LNS is self-injurious behavior, which typically manifests as biting of the lips, fingers, or other body parts. This behavior is thought to be related to abnormalities in the basal ganglia and may be driven by a combination of neurological dysfunction and compulsive tendencies.
3. Intellectual disability: Individuals with LNS often have intellectual disability ranging from mild to severe. Cognitive impairment can affect various aspects of functioning, including learning, communication, and social interaction.
4. Hyperuricemia: Due to the deficiency of HPRT, there is an overproduction of uric acid, leading to elevated levels of uric acid in the blood (hyperuricemia). This can result in gouty arthritis and the formation of uric acid crystals in the joints and kidneys.

Lesch-Nyhan syndrome is inherited in an X-linked recessive pattern, meaning it primarily affects males. Females who carry one copy of the mutated gene typically do not display symptoms but can pass the gene on to their children. There is currently no cure for LNS, and treatment focuses on managing symptoms and providing supportive care to improve quality of life. This may include medications to control movement disorders, behavioral therapy, and interventions to address complications such as gout and kidney stones.