Chapter 16- Fatty Acids and Eicosanoids Flashcards
What is a positive modulator of lipolysis?
glucagon or epinephrine
What does CPTI do?
transport acyl-CoA into mitochondria
What is lipolysis?
hydrolysis of TAGs in adipocytes -> forms free FA
what is a negative modulator of CPTI?
malonyl-CoA
In ketogenesis Fatty acyl-CoA can be converted to
2 Acetyl-CoA or Acetoacetyl-CoA (beta-oxidation)
Acetoacetyl-CoA is synthesized from what?
2 acetyl-CoA catalyzed by thiolase in starvation
In fed state what is the fate of acetyl-CoA?
TCA cycle -> glucose via gluconeogenesis
In ketogenesis what is acetoacetyl-CoA converted to and by what enzyme?
HMG-CoA via HMG-CoA synthase
In ketogenesis what is HMG-CoA converted to and by what enzyme?
Acetoacetate via HMG-CoA lyase
In ketogenesis what is Acetoacetate converted to and by what?
spontaneously decarboxylated to acetone
converted to 3-hydroxybutyrate via 3-hydroxybutyrate dehydrogenase
Are ketones used by the liver?
No, the liver lacks succinyl-CoA-acetoacetate-CoA transferase so it cannot use ketone bodies
How does the body use ketone bodies?
when ketone bodies released from liver -> transported to muscle (major), kidney (major), brain (only in starvation) -> oxidized for energy
What is the rate limiting step in ketogenesis?
HMG-CoA reductase, release of FA from adipose and uptake of acyl-CoA into mitochondria (CPTI)
where does cholesterol synthesis occur?
liver cytosol
Where does ketogenesis occur
liver mitochondria
How is acetone excreted?
by lungs, expiration
How are ketone bodies excreted?
urine
Why does ketogenesis occur?
During gluconeogenesis acetyl-CoA uses oxaloacetate in the formation of citrate and eventually glucose. When oxaloacetate is depleted ketogenesis proceeds so acetyl-CoA can be utilized for energy.
Where is the major site of FA synthesis?
liver cytosol
Synthesis of long chain saturated FA is from?
Synthesized from dietary glucose via pyruvate
Where are enzymes for FA synthesis located?
The Es are localized in the cytosol, completely different from the mitochondrial Es for FA degradation
To synthesize palmitic acid, polymerization of initial 2 carbon units are from what
Acetyl-CoA, carbons 15, 16
What molecules are required for FA synthesis?
reduced NADPH, ATP, biotin, CO2, H2O
What is the initial and controlling step of FA synthesis?
production of Malonyl-CoA, carboxylation reaction and requires biotin
Describe FA synthase
a multi-enzyme complex, total of 8 reactions
General concept of LCFA synthesis?
keep adding 2 carbon until C16 (palmitic acid) then enzyme no longer has affinity and releases FA
How is acetyl-COa transported out of the mitochondria to be used for FA synthesis?
as citrate
Where do the additional 2 carbons that add onto acetyl-CoA’s initial carbons come from?
malonyl-CoA, carbons 1-14
What are 4 essential unsaturated FA
palmitoleic acid (16:1)
oleic acid (18:1)
linoleic (18:2)
alpha-linolenic (18:3)
What do cis USFA provide?
fluidity of TG reserves, phospholipid membranes
Many serve as precursors of eicosanoids (prostaglandins, prostacyclins, thromboxanes, & leukotrienes)
Where and how are double bonds introduced
In the ER, double bonds are introduced between carbons 9 and 10 by FA oxygenase, which require molecular oxygen (O2) and NADPH
Arachidonic acid is the precursor of
PGs, TXs, PGIs, & LTs
Essential fatty acids are stored almost completely as
esters of the 2-position of the glycerol backbone of cell membrane phospholipids
essential fatty acids are released using what phospholipase in arachidonic acid synthesis?
phospholipase A2
Activation of PLA2 and PLC
Stimuli -> intracellular Ca2+ with calmodulin -> activate membrane bound phospholipase A2 and C
What drug inhibits phospholipase A2 activity?
glucocorticoids (i.e. cortisol)
Phospholipase A1 cleaves
at SN-1, first acyl group on glycerol backbone
Phospholipase A2 cleaves
at SN-2, first acyl group on glycerol backbone
Phospholipase C cleaves
cleaves phospholipids just before phosphate group
Phospholipase D cleaves
cleaves just after phosphate group freeing serine or choline or inositol or ethanol amine
name two Cox-2 inhibitors
celecoxib
rofecoxib
What is monteleukast used to treat?
treatment of allergen and exercise-induced asthma and allergic rhinitis
MOA of Zarfirlukast or monteleukast
leukotriene receptor antagonist
Biological activities of PGD2
inhibits platelet and leukocyte aggregation, decreases T-cell proliferation and lymphocyte migration and secretion of IL-1a and IL-2; induces vasodilation and production of cAMP
Biological activities of PGE2
increases vasodilation and cAMP production, enhancement of the effects of bradykinin and histamine, induction of uterine contractions and of platelet aggregation, maintaining the open passageway of the fetal ductus arteriosus; decreases T-cell proliferation and lymphocyte migration and secretion of IL-1a and IL-2
Biological activities of PGF2alpha
increases vasoconstriction, bronchoconstriction and smooth muscle contraction
Biological activities of PGH2
precursor to thromboxanes A2 and B2, induction of platelet aggregation and vasoconstriction
Biological activities of PGI2
inhibits platelet and leukocyte aggregation, decreases T-cell proliferation and lymphocyte migration and secretion of IL-1a and IL-2; induces vasodilation and production of cAMP
Biological activities of TxA2
induces platelet aggregation, vasoconstriction, lymphocyte proliferation and bronchoconstriction
Biological activities of TxB2
induces vasoconstriction
Biological activities of LTB4
induces leukocyte chemotaxis and aggregation, vascular permeability, T-cell proliferation and secretion of INF-γ, IL-1 and IL-2
Biological activities of LTC4
component of SRS-A, microvascular vasoconstrictor, vascular permeability and bronchoconstriction and secretion of INF-γ
Biological activities of LTD4
predominant component of SRS-A, microvascular vasoconstrictor, vascular permeability and bronchoconstriction and secretion of INF-γ
Biological activities of LTE4
component of SRS-A, microvascular vasoconstrictor and bronchoconstriction
What is tested/detected in asthmatic reactions?
LTE4
