Bioactive Lipids (III) Flashcards
Bioactive Lipid Mediators \_\_\_\_ \_\_\_\_ \_\_\_\_ \_\_\_\_
Redness
Heat
Swelling
Pain
Bioactive Lipids
– Bioactive mediators possess both ____ and ____ properties.
– Bioactive lipids are formed from a series of reactions in which ____ is added to the acyl chain.
– The acyl chains are derived from ____ (20:4), ____ (20:5) or ____ (22:6).
pro anti inflammatory molecular oxygen (O2) AA EPA DHA
Arachidonic Acid Metabolism
• Major points:
– Arachidonic acid, the parent compound to the ____ can be synthesized from essential FA ____ (details in FA synthesis lecture, slide 29).
– Eicosanoids are formed from a series of reactions in which ____ is added to arachidonate.
– The resulting biological signaling molecules act as potent short range messengers. ____ and ____ signals
– The physiological response is often an indication of the ____ of these mediators.
eicosanoids
linoleate
molecular oxygen (O2)
autocrine
paracrine
ratio
The Eicosanoids (eicosa-20 in greek, synthesized from AA)
• Prostaglandins- 20C compounds, with a ____ internal ring. Biologically active- ____ at C15 and ____ C13-14.
- Thromboxanes-20C compounds with a ____ ring containing an ____ between C9 and 11.
- Leukotrienes- 20C compounds with ____ ring structure and insertion of ____ (to form OH) a C 5, 12 or 15.
5C
OH
double bond
5C
oxygen
no
oxygen
Arachidonic Acid Release Upon Stimulation
Phospholipase A2 activity (inhibited by ____)
Phospholipase C and DAG lipase activity
glucocorticoids
The first step in the synthesis of prostaglandins and thromboxanes is ____ the remainder are ____.
____ is the common intermediate
common (ubiquitous)
tissue specific
PGH2
____ secretes Prostacylcin, a potent ____. This is a ____ signal
Platelets upon activation secrete an ____ signal in the form of
____ to initiate aggregatory stimulus
vascular endothelium
anti-aggregatory compound
paracrine
autocrine
TXA2
COX 1: Inhibition by aspirin is- ____
COX2: Inhibition by NSAIDS is ____
• COX-1, ____ active, responsible for ____ activities.
• COX-2, ____, “as needed” ____ levels increased in inflamed tissue, is generated in response to ____
irreversible reversible constitutively "housekeeping" inducible mRNA inflammation
Most Prostaglandins and Thromboxanes signal through ____
GPCR
Cyclo-oxygenase -COX
Characteristics: ____, Homodimer, ____, ____- containing enzyme
glycosylated
membrane bound
heme
Leukotrienes
• Least well ____ of the eicosanoids.
• Most unstable of the eicosanoids have a T1/2 of less than ____ secs
characterized
30
Omega fatty acids
 The omega fatty acids are derived from the ____ and are provided by the ____ in foods such as fish and plant oils
essential FA
diet
Bioactive lipids derived from EPA and DHA acid
• Resolution of ____ is an active process utilizing eicosanoids, lipoxins, resolvins and protectins.
• Preferentially use ____
• These are ____
resolving compounds. Double hit.
• Responsible for protection against ____ or resolution of inflammatory response
acute inflammation
omega-3 PUFA
anti-inflammatory - pro-resolving compounds
oxidative stress
The Protectins • Derived from \_\_\_\_ (22:6) • Have a conjugated \_\_\_\_ double bond • Synthesized in a \_\_\_\_ mediated pathway • Protects numerous cells from \_\_\_\_.
DHA
triene
lipoxygenase
oxidative stress
Inflammation
Protective response against harmful stimuli including pathogens (bacteria, viruses, fungi, etc) and injury (trauma, chemical, UV, etc)
Involves ____ and other immune components such as ____
Stimulates ____ to wounding to initiate healing
Causes damage when not properly ____
leukocytes
complement
early response
regulated
Synthesis of Resolvins
First step of resolvin synthesis requires an acetylated ____ enzyme.
acetylated COX-2
Periodontal Disease and Resolvins I  Gingivitis (\_\_\_\_ of gingiva) Periodontitis (loss of \_\_\_\_) - Loss of connective tissue attachment between tooth and gingiva - Loss of bone supporting the tooth
• Initiated by bacteria • Damage is caused by the \_\_\_\_ to bacteria (not \_\_\_\_ by bacteria) • Several bacteria have been proposed to contribute to periodontal disease. • Two putative pathogens • \_\_\_\_ - \_\_\_\_ pathogen • \_\_\_\_
inflammation supporting structure inflammatory response directly P. gingivalis (Pg) Keystone A. Actinomycetemcomitans (Aa)
Periodontal Disease and Resolvins II
Disease induced in rabbit model

Resolution of Inflammation is mediated by bioactive lipids derived from EPA or DHA called ____.
Topical application of ____ analog restored lost soft tissue and bone to healthy levels
resolvins
RvE1
Osteoclast density and inflammatory cell infiltration in the RvE1 groups were ____ than those in the placebo group.
RvE1 treatment ____ expression of inflammation-related genes, returning the expression profile to one more similar to health.
Treatment of established periodontitis with RvE1 ____ bone loss, ____ inflammatory gene expression, and ____ osteoclast density.
lower
reduced
reversed
reversed
reduced
Anecdotally based on patient history there was a perceived correlation between increase dietary intake of ____ and decreased ____.
However, present study findings largely support benefits of ____ through non- bacteriologic pathways.- might help host- cell -resolvins
DHA
periodontal disease
n-3s
Take Home Lessons
• Arachidonic acid is supplied in ____ and serves as a precursor for ____. Eicosanoids are a family of ____ involved in both normal and patho-physiological responses.
• EPA and DHA serve as precursors for the ____ and the ____. The synthesis of these compounds requires ____
membrane lipids
eicosanoids
inflammatory mediators
resolvins
protectins
acetylated COX2
