Eicosanoid Flashcards
1
Q
Are autocrine and paracrine hormones
A
EICOSANOIDS
2
Q
Family of very potent biological signaling
molecules that act as short- range messengers
A
Eicosanoids
3
Q
Eicosnoids are Synthesized by C20 eicosanoic acids what are the three:
A
-arachidonate,
-timnodonate
-dihomo γ-linolenate
4
Q
Eicosanoids are composed of 3?
A
prostanoids, leikotrienes & lipoxins
5
Q
Effects of intracellularly mediated by cAMP
Have very short half- lives, they are rapidly
inactivated and excreted
A
Eicosanoid
6
Q
These are prostanoids
A
-Prostaglandins
- Prostacyclins
- Thromboxanes
7
Q
Physiological effects of prostanoids
A
- Inflammatory responses
- Production of pain & fever
- Regulation of blood clotting
- Induction of labor
- Regulation of the sleep/ wake cycle
- Inhibition of gastric secretion
- Contraction of intestinal smooth muscles
8
Q
First identified in human semen by Ulf von Euler
in 1930
A
Prostaglandins
9
Q
2 original groups defined in prostaglandins:
A
PGE & PGF
10
Q
3 major classes of prostaglandins
A
-PGAs- α & β unsaturated -ketones PGEs- β OH ketones
-PGF- 1-3diols
11
Q
Tre or false
Prostaglandin A has alpha and beta unsaturation. Subscripts 1 and 2 are the number of double bonds outside the ring system.
-
A
True
12
Q
- 8, 11, 14 eicosatrienoic acid
- Series 1 prostaglandins
A
Dihimo γ - linolenic acid
13
Q
- 5, 8, 11, 14, 17 eicosapentaenoic acid
- Series 3 prostaglandins
A
Timnodonic acid
14
Q
Thru this rxn linoleic acid can be converted to γ - linoleic acid, and with the use of enzyme elongase, it can be lengthen by adding 2 carbons giving rise to dihomo- γ - linolenic acid; this can be dehydrogenated to form arachidonic acid.
A
Dehydroenation
15
Q
Present in membranes (5- 15% in phospholipidS)
A
ARACHIDONIC ACID
16
Q
Most important precursor of prostaglandin in humans
- Polyunsaturated fatty acid
A
ARACHIDONIC ACID
17
Q
- 4 nonconjugated double bonds
- 5, 8, 11, 14 eicosatetraenoic acid
A
ARACHIDONIC ACID
18
Q
Arachidonic acid are synthesized from what?
A
essential fatty acid
linoleic acid (ω - 6 fatty acid)
19
Q
Arachidonic acid is released into the cell, it is
converted to
A
Eicosanoids
20
Q
Acts on carbon 2 where arachidonic acid is
attached
A
Phospholipase A
21
Q
Phospholipase A will then be released and acted upon by?
A
cyclooxygenase
22
Q
Acts on attached phosphate and head group
of nitrogenous base
A
Phospholipase C, diacylglycerol kinase
23
Q
True or false
In some books, arachidonic acid is produced
Indirectly
A
False
Directly
24
Q
True or falase
phospholipase A2 is still needed for the production of arachidonic acid
A
True
25
Not associated with other
Diacyglycerol lipase
26
2 MAJOR PATHWAYS OF ARACHIDONATE METABOLISM
CYCLOOXYGENASE PATHWAY
LIPOXYGENASE PATHWAY
27
Thru cyclooxygenase activity and with the help of oxygen, there will be;
Cyclization
28
True or gqse
By mean of a peroxidase activity, there will be reduction to form hydroxyl substituent forming prostaglandin H2
Formation of prostaglandins and thromboxanes
Prostaglandin: 20C fatty acids, with internal 5- carbon ring; biologically active prostaglandin has a hydroxyl group at C15, double bond between C13 and C14
True
29
biologically active prostaglandin has a
hydroxyl group at C15, double bond between C13 and C14
30
Thromboxanes: contain a how many- membered ring with oxygen atom
6
31
True or fals
TXA2 contains additional oxygen atom attached to both C9 and C11 of the ring
True
32
BIOSYNTHESIS STEPS
Cyclooxygenase forms the five- membered ring and adds 4 atoms of oxygen (2 between 9, 11 and 2 at C25) to form the unstable endoperoxide (PGG2). Hydroperoxy group at C5 is quickly reduced to a hyrdroxyl group by peroxidase to form another endoperoxide (PGH2)
2. Depending on the cell type involved, PGH2 may be reduced to PGE2 or PGD2 by PGE/PGD synthase
3. PGE2 may be reduced to PGF2α by PGE 9- ketoreductase
4. PGF2α may be directly form from PGH2 by endoperoxide reductase
5. PGH2 may be converted to thromboxane A2 by TXA synthase (high in platelet). PGH2 is converted to prostaglandin PGI2 by PGI synthase
33
oxidizes the heme iron.
Peroxide
34
The oxidized heme accepts an electron from
tyrosine residue
35
may initiate prostaglanfin synthesis by reacting with superoxise anion (O2) to produce peroxynitrite,
nitric oxide,
36
oxidizes the heme iron enabling electron
transfer from the active site tyrosine
peroxynitrite
37
True or false
Prostaglandin synthesis in response to some
inflammatory stimuli is diminished by inhibitors of b) nitric oxide synthase
True
38
2 isoforms of cyclooxygenase
COX-1 and COX- 2
39
isoforms of cyclooxygenase that is constitutively expressed
Cox-1
40
isoforms of cyclooxygenase that is made only in response to inflammatory
mediators such as cytokines
Cox-2
41
True or false
Cox-1 is only inhibited by non- specific NSAIDs such
as aspirin, ibuprofen and mefenamic acid
False
Both cox-1 and cox-2
42
Major side effects of blocking COX-1 activity
gastritis and GI bleeding
43
This 2 blocks cox-2
COX-2
specific inhibitors
Celecoxib and rofecoxib
44
True or false
cox-1 specific inhibitors don‟t cause gastric
irritation and bleeding
False
Its cox-2
45
acts as reversible
inhibitors of cyclooxygenase
Acetaminophen, ibuprofen
46
are generated out of the action of thromboxane synthase, initially TxA2 but due to structure instability, it will melt into TxB2
Thromboxanes
47
Produced by endothelial cells of blood vessels Causes vasodilation
PROSTACYCLIN (PGI2)
48
-Inhibits platelet aggregation
- Increases formation of cAMP
PROSTACYCLIN (PGI2)
49
-Produced by most tissues
- Causes vasoconstriction
- Contraction of smooth muscle
- Stimulates uterine contraction
PROSTAGLANDIN F2a (PGF 2a)
50
Produced primarily by platelets Promotes platelet aggregation
Decreased formation of cAMP Cause vasoconstriction
THROMBOXANE A2 (TXA2)
51
4 short amphipathic alpha- helices that insert into one leaflet of the bilayer, facing the ER lumen
Membrane binding domain
52
True or false
Acetylation of a serine residue in the active site of cyclooxygenase, reversibly inactivating it
False
Irreversibly
53
derived from membrane lipids approaches the heme via a hydrophobic channel extending from the membrane- binding domain
Arachindonate
54
True or false
Non- steroidal anti- inflammatory drugs (NSAIDs) such as aspirin and derivatives of ibuprofen inhibits cyclooxygenase activity of PGH2 synthase
True
55
- They inhibit formation of prostaglandins involved in fever, pain & inflammation
- They inhibit blood clotting by blocking
thromboxane formation in blood platel
NSAIDS
56
block the hydrophobic channel by which arachidonate enters the cyclooxygenase active site
Ibuprofen
57
Prostaglandins are inactivated by
oxidation of the 15- hydroxyl group to a ketone.
58
True or false
Single bond at C13 is reduced both β- and ω- oxidation of the nonring portions occur, producing dicarboxylic acids that are excreted in the urine
False
Double bond
59
rapidly metabolized to TXB2 by cleavage of the oxygen bridge between C9 and C11 to form hydroxyl group.
Active TXA2
60
Examples of lipoxygenase pathway
polymuphonuclear leukocytes contains 5- lipoxygenase, platelets contains 12- lipoxygenase, eosinophilic leukocytes contain 15- lipoxygenase
61
Begins with the formation of hydroperoxyeicosatetraenic acid (HPETEs)
LEUKOTRIENE SYNTHESIS
62
are synthesized in leukocytes and contain the typical triene structure (3 double bonds; position 7, 9, 11)
Leukotrienes
63
Other functional leukotrienes are formed from
_______ by different pathways
LTA4
64
What pathway : LTA4 is converted to LTB4, a 5, 12-
dihydroxy derivative
Pathway 1
65
What pathway that involves the addition of reduced
gluthathione to C6 to form LTC4 by an enzyme, glutathione S- tranferase
Pathway 2
66
Formed through the action of 15- lipoxygenase followed by the action of 5- lipoxygenase on arachidonic acid
LIPOXIN SYNTHESIS
67
Is formed thru a series of reductions of the resultant hydroxyperoxy groups
LIPOXIN SYNTHESIS
68
LIPOXIN SYNTHESIS
Induces chemotaxis and stimulates superoxide anion production in what
leukocytes
69
-Contraction of smooth muscle
- Bronchoconstriction
- Vasoconstriction
- Increased vascular permeability
- Components of slow- reacting substances of
anaphylaxis (SRS- A)
Peptidoleukotrienes (LTC4, LTD4, LTE4)
70
- Increases chemotaxis of polymorphonuclear
leukocytes
- Induces release of lysosomal enzymes
- Promotes adhesion of WBC
Leukotriene B4
71
Leukotriene B4 stimulates what enzyme
adenylate cyclase
72
Family of conjugated tetraenes also arising
leukocytes
LIPOXINS (LXA4)
73
Exhibit vasoactive and immunoregulatory function
LIPOXINS (LXA4)
74
Precursors for synthesis of proteins
- Replace worn out body tissue proteins
- Source of energy
- Detoxification of drugs chemicals & metabolic by
products
- As direct neurotransmitters or as precursors to
neurotransmitters
Functions of proteins & Amino Acids
75
True or false
Functions of proteins & Amino Acids in the Body
-Precursors to peptode hormones &thyroid hormones
- Precursors to histamine, NAD, serotonin, Glutathione
True
76
Represents the total anino acids in the body derived from dietary sources and from breakdown of tissue proteins
Amino Acid Pool
77
Serves two major purposesof Amino Acid Pool
- As substrates for synthesis of proteins & other
nitrogen containing compounds
- Important fuel for ATP production
78
Replacement of body protein by synthesis & degradation
Protein Turnover
79
Represents process in which proteins are degraded into amino acids
Catabolism
80
rate wherein amino acids are converted to proteins
Anabolism
81
Reflects the difference between nitrogen intake and its excretion
Nitrogen Balance
82
net increase in body protein content
Positive nitrogen balance
83
more nitrogen is excreted than ingested
Negative nitrogen balance
84
half-life of a protein
Examples
hour or less
ornithine decarboxylase, phosphokinase C, and insulin,
—several months, such as for hemoglobin, collagen, and histones
—life of the organism, such as for the crystallins of the lens.
85
majority of body protein, and consequently of amino acids, is in?.
skeletal muscle
86
protein is degraded and amino groups from the amino acids are transferred to glutamine and alanine. True or false
True
87
Urea for excretion
Ureotelic
Terrestrial vertebrates
88
Uric acid for excretion
Uricotelic
Birds reptiles
89
Ammonium for excretion
Ammonotelic
Aquatic animals
90
reactions interconvert pairs of α- amino acids and α-keto acids
Transamination
91
occurs via a “ping-pong” mechanism characterized by the alternate addition of a substrate and release of a product
Transamination
92
True or false
Transamination reactions, which are freely irreversible, also function in amino acid biosynthesis
False
Reversible
93
a derivative of vitamin B6, is present at the catalytic site of all
Pyridoxal phosphate (PLP)
94
serves as a “carrier” of
amino groups.
Pyridoxal phosphate (PLP)
95
formed between the
oxo group of enzyme- bound PLP and the α-amino group of an α-amino acid.
enzyme-bound Schiff base
96
regulated allosterically by purine nucleotides
Glutamate dehydrogenase
97
convert an amino acid to an α-imino acid that decomposes to an α-keto acid with release of ammonium ion
L-Amino acid oxidase of liver and kidney
98
The reduced flavin is reoxidized by molecular oxygen, forming hydrogen peroxide (H2O2), which
then is split to O2 and H2O by what
Catalase
99
is one of the amino acids with various degradative pathways chat are determined by physiological needs and conditions.
Serine
100
DISPOSAL OF AMMONIA
Alanine Cycle
Glutamine Cycle
Urea Cycle
101
There are two human isoforms of mitochondrial glutaminase,
liver-type and
renal-type glutaminase.
102
collects nitrogen from other amino acids by transamination reactions.
Glutamate
103
provides one of the nitrogens for urea synthesis
NH4
104
catalyzes the formation from acetyl-CoA
N-Acetylglutamate synthase, NAGS
105
essential for carbamoyl phosphate synthase I activity.
N-Acetylglutamate synthase, NAGS
106
Treatment for Hyperammonemia in UCD
- Reduce protein in the diet
- Removal of excess ammonia
- Replacement of missing intermediates of the
cycle
- Administration of levulose
- Antibiotics
- Administration of sodium benzoate & sodium
phenylbutyrate
107
Purely Glucogenic Amino Acids
Alanine
- Arginine
- Asparagine
- Aspartate
- Cysteine
- Glutamate
- Glycine
- Histidine
- Methionine
- Proline
- Glutamine
- Serine
- Valine
108
amino acids which can be converted to glucose, pyruvate or a TCA cycle intermediate
Glucogenic Amino Acids
109
amino acids which can be converted to acetyl CoA or acetoacetyl CoA
Ketogenic Amino Acids
110
solely ketogenic
leucine and lysine
111
Both Glucogenic & Ketogenic Amino Acids
- Isoleucine
- Phenylalanine
- Tryptophan
- Tyrosine
- Threonine
112
mammals lack a path- way for the net synthesis of glucose from acetyl CoA or acetoacetyl CoA.
True
113
Inborn Errors of Metabolism
- Usually inherited as
autosomal recessive trait
114
Amino Acids Catabolized via Pyruvate
- Alanine
- Serine
- Glycine
- Cysteine & cystine
- Threonine
- Tryptophan
- Hydroxyproline
115
amino group of alanine is transferred to a- ketoglutarate to form what
glutamate
