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21 Cards in this Set

  • Front
  • Back

What is phosphatidylcholine (PC) cleaved into by phospholipases?

- PLA2 cleaves it into arachidonic acid

- PLA2 is stimulated by interferons, epiephrine, thrombin, histamin and othrs

Arachidonic acid is metabolised by three major pathways to produce what?

- eicosanoids

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

What cells produce eicosanoids?

- all cells except erythrocytes

- major producers include macrophages and mast cells

Examples of biological effects of eicosanoids:

- in inflammation and fever

- modulate smooth muscle contractions

- effect blood clotting

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

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

How do eicosanoids affect blood clotting?

- PG and TX inhibit and stimulate platelet aggregation respectively

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

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

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

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

What is a protein kinase?

- Enzyme that modifies other proteins by the addition of a phosphate group

What does phosphorylation result in?

- conformational change leading to functional change

- rapid occurrence of highly amplified events

What are the two classes of protein kinases?

- Serine/threonine kinases

- Tyrosine kinases

What are some examples of serine/threonine kinases?

- they are all cytoplasmic

- Protein kinase B (Akt)

- Mitogen-activated protein kinase (MAPK)

- Protein kinase A

What are some examples of tyrosine kinases?

- Receptors - HER family; IGF-1R

- Cytoplasmic - Janus kinase (JAK), Src

The akt family have three main domains. What are they?

- Pleckstrin homology - PH (recognition)

- Catalytic kinase domain

- regulatory C-terminal domain

How is Akt activated?

- PI3 kinase produced PIP3, which facilitates phosphorylation of Akt by PDK1

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)

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