• Also called cyclooxygenase (COX), main

catalytic function is the conversion of arachidonic

acid to prostaglandin H2 (PGH2)

•Monotopic integral membrane proteins: bind to

luminal leaflet of ER membrane and nuclear

membrane

•Implications in thrombosis, inflammation,

neurological disorders,and cancer.

•Great deal of attention as the target of non-

steroidal anti-inflammatory drugs (NSAIDs)

Prostaglandin H2 synthase

2

Eicosanoids: paracrine hormones

• Derived from the 20 carbon polyunsaturated fatty acid

(arachidonic acid)

• Involved in reproduction, inflammation, fever and pain

• 3 classes: Prostaglandins, thromboxanes, leukotrienes

Regulate synthesis of cAMPproduction fever, pain, blood flow, and uterine contraction

Produced by platelets, important in clotting and blood flow

Inflammation, asthma, allergy

• Epithelial growth factor (EGF) domains (red), membrane

binding domains (yellow), and catalytic domains (blue and gray).

Figure 9.4 Structure of a PGHS monomer, showing

POX and COX active sites

• Each monomer has 3 domains:

catalytic domain (blue) has two active

sites the POX (top of heme) and the

COX (bottom)

•Arachindonic acid (yellow space fill) is

bound between these

•Membrane binding domain (orange)

below arachindonic acid

•Epidermal growth factor (green) is on

the side that becomes the subunit

interface in the dimer.

NSAIDS

•Many NSAIDS act as competitive inhibitors

•They prevent substrate binding by occupying the upper part of the COX

channel

•Interactions between the drugs and the enzyme are hydrophobic

•Exceptions being the interaction of the acidic NSAIDs with Arg120 and

potential of a hydrogen bond with Ser530

Eicosapentaenoic acid (20:5ω-3)

Omega-3 Fatty Acids

Phospholipid membrane

Phospholipase A2

Cyclooxygenases (COX)

Prostaglandins (PG)

&

Thromboxanes (TX)

Lipoxygenases (LOX)

Leukotrienes

O

HO

O

HO

Arachidonic acidEicosapentaenoic acid

-poor substrate for cyclooxygenases

-gives rise to series 5 leukotrienes

G protein-coupled receptors

• GPCRs respond to chemicals, light or odor and activate

G proteins to initiate signal cascades

– Prototype rhodopsin

– Share a common structure of seven TM helices

• Mechanosensitive (MS) channels transduce physical

perturbations of the membrane into chemical and

electrical signals

Generalize function of GPCR

•Respond to a variety

of stimuli including :

light, odorants,

calcium ions, small

molecules and

proteins

•Trigger activation of

the αβγ complex

which stimulates the

release of second

messengers

Rhodopsin

• located in rod cells of

the eye

•Rhodopsin consists of

an apoprotein called

opsin and a

chromophore, 11-cis

retinal

•Bovine rhodopsin spans

the membrane with seven

α-helices with its C-

terminus in the cytosol

and its N-terminus on the

exo-cytoplasmic surface

•The seven helices have

highly conserved

residues at key positions

12

• Converted to active form

• Regulates response of rod and cone cells in the retina to light

• Regulates gene expression of development of epithelial tissue

• Used to treat severe acne, wrinkled skin