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21 Cards in this Set
- Front
- Back
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What is phosphatidylcholine (PC) cleaved into by phospholipases? |
- PLA2 cleaves it into arachidonic acid - PLA2 is stimulated by interferons, epiephrine, thrombin, histamin and othrs |
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Arachidonic acid is metabolised by three major pathways to produce what? |
- eicosanoids |
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What are the three different types of eicosanoids? |
- prostanoids e.g. prostaglandins (PG), thromboxanes (TX) (produced by action of cyclooxygenase pathway Cox) - leukotrienes (LT) - produced by the 5-lipooxygenase pathway 5-Lox - EETs, HETEs, HPETEs - produced by cytochrome p450 monooxygenase pathway |
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What cells produce eicosanoids? |
- all cells except erythrocytes - major producers include macrophages and mast cells |
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Examples of biological effects of eicosanoids: |
- in inflammation and fever - modulate smooth muscle contractions - effect blood clotting |
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What is the effect of eicosanoids in fever and inflammation? |
- PG and LT act as vasodilators (redness)
- LT increases blood vessel permeability (swelling) - PG sensitise nociceptors (pain) and act as pyretic agents (heat) - LT recruit WBC to site of tissue damage/infection |
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How to eicosanoids modulate smooth muscle contraction? |
- LT cause tracheal sm contraction (increased in asthma) - PG cause uterine contractions - regulate blood pressure via blood vessel sm constriction |
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How do eicosanoids affect blood clotting? |
- PG and TX inhibit and stimulate platelet aggregation respectively |
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What are the features of the Cox enzymes? |
- Cox1 involved in the synthesis of prostanoids - PG; constitutively expressed in most tissues - Cox2 - induced by growth factors; linked to pathophysiological conditions such as cancer; induced by oncogenic events |
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What medicine can be used to inhibit Cox activity? |
- NSAIDS - nonsteroidal anti-inflammatory drugs e.g. aspirin - anti-pyretic, anti-inflammatory - side effects - stomach ulcers due to Cox1 inhibition; - long-term intake reduces risk of colorectal cancer - related to Cox2 inhibition |
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How do PG and TX exert their cellular effects? |
- exit the cell via efflux transporters - bind mainly to cell surface receptors - act via autocrine and paracrine signalling |
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How does the 5-Lox pathway of LT synthesis work? |
- Arachidonic acid is converted into 5-HPETE - 5HPETE is metabolised into LTA4 (unstable) - LTA4 is converted into several LTs |
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What is a protein kinase? |
- Enzyme that modifies other proteins by the addition of a phosphate group |
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What does phosphorylation result in? |
- conformational change leading to functional change - rapid occurrence of highly amplified events |
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What are the two classes of protein kinases? |
- Serine/threonine kinases - Tyrosine kinases |
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What are some examples of serine/threonine kinases? |
- they are all cytoplasmic - Protein kinase B (Akt) - Mitogen-activated protein kinase (MAPK) - Protein kinase A |
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What are some examples of tyrosine kinases? |
- Receptors - HER family; IGF-1R - Cytoplasmic - Janus kinase (JAK), Src |
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The akt family have three main domains. What are they? |
- Pleckstrin homology - PH (recognition) - Catalytic kinase domain - regulatory C-terminal domain |
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How is Akt activated? |
- PI3 kinase produced PIP3, which facilitates phosphorylation of Akt by PDK1 |
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How is Akt regulated? |
- By PTEN (which dephosphorylates PIP3 and PIP2, thus not facilitating PDK1 in phosphorylating Akt) - directly dephosphorylated ny PHLPP (PH domain and Leucine rich repeat Protein Phosphatase) |
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Akt also phosphorylate a family of transcription factors. What is it and how does that affect it? |
- FOXO family - prevents it from entering the nucleus = inhibiting FOXO sensitive genes |
