Eicosanoids Flashcards
Phases of inflammation
Acute phase of inflammation includes infiltration by granulocytes (neutrophils) followed by monocytes that mature into macrophages. This process causes the four cardinal signs of inflammation: rubor (redness), calor (heat), tumor (swelling), and dolor (pain)
Four cardinal signs of inflammation
Rubor (redness), calor (heat), tumor (swelling) and dolor (pain)
Prostaglandins
synthesis dramatically increases during inflammation
proinflammatory and may be important in resolution of inflammation
inhibitors of prostaglandin synthesis are anti-inflammatory
Prostaglandins are members of the eicosanoids
Examples of eicosanoids
Prostaglandins, thromboxanes, and leukotrienes
How are eicosanoids made?
They are made from 20 C polyunsaturated fatty acids
They are in cell membrane phospholipids and released by phospholipases
They are made by most cell types (except RBCs)
The precursor is arachidonic acid (which can be synthesized from linoleate) (Some prostaglandins use EPA (eicosapentaenoic acid) as a precursor)
Precursor of eicosanoids
arachidonic acid (which can be synthesized from linoleate) some prostaglandins use eicosapentaenoic acid (EPA) as a precursor (linolenic acid can be used to synthesize eicosapentaenoic acid)
Synthesis of arachidonic acid from linoleate
delta6-desaturase uses linoleoyl-CoA, oxygen, and NADH (and a proton) to make gamma-linolenoyl-CoA (and water and NAD+). This is elongated in the ER and uses malonyl CoA to make Dihomo-gamma-linolenoyl-CoA. Delta6-desaturase then uses oxygen and NADH (and a proton) to make Arachidonoyl-CoA
The desaturase for the synthesis of arachidonic acid is located in ___.
cytochrome b5
Triene:Tetraene ratio
marker for essential fatty acid deficiency
>0.4 indicates deficiency
Mead’s acid:Arachidonic
Linoleic acid can be a precursor for ___.
EPA (eicosapentaenoic acid)
Omega 3 and omega 6 fatty acids both compete for the same ______.
delta 5 and delta 6 desaturases
Important because ingestion of more omega 6 fatty acids may lead to more inflammation
Release of arachidonic acid induced by ____.
binding to a receptor (e.g. cytokines)
Phospholipase A2 releases arachidonic acid in response to cellular signals that trigger making eicosanoids
What does phospholipase C activity do?
releases phosphatidyl inositol (PIP) (which according to the notes has something to do with a second signal that creates DAG, which can also break down into arachidonic acid)