Paracrines Derived from Polyunsaturated Fatty Acids

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1

arachidonic acid, eicosanoids

An important family of regulatory molecules is derived from _________________, and these molecules collectively are often called the ____________.

2

eicosanoids

We will encounter what molecules in the areas of inflammation and hemostasis?

3

phospholipase A2 (PLA₂)

The formation of eicosanoids molecules begins with a stimulus to a cell that activates a membrane enzyme called ____________.

4

cyclooxygenase (COX), lipoxygenase (LOX)

The arachidonic acid released from the phospholipid is now the substrate for one of two enzymes. The first enzyme is __________________ and the second enzyme is ______________.

5

prostaglandin, thromboxane

The product of the arachidonic acid converts into COX₂ then proceeds through a further sequence of enzymatic reactions to produce a regulatory molecule that is either a ___________ or _______________ .

6

leukotrienes

The second possibility is for lipoxygenase (LOX) to act on the arachidonic acid. In this pathway, the actions of further enzymes lead to regulatory molecules in the family of the ______________.

7

paracrines

All of the eicosanoid regulatory molecules tend to act locally as _____________.This is because they are degraded too rapidly to move about the body through the circulatory system.

8

paracrines

local hormones that act on neighboring cells

9

cyclooxygenase COX₁ & COX₂

The familiar and widely used nonsteroidal anti-inflammatory drugs (NSAIDS), such as aspirin, ibuprofen, and naproxen, are inhibitors of ______________.

10

COX1, inhibit the secretions of stomach acid.

_______ is found widely in the body and tends to be expressed constantly as a normal part of the functioning of the body. It is especially common in the digestive tract. Notably, in the stomach it produces prostaglandins that __________________________________.

11

COX2

________is released mainly by special, inflammatory cells, and its expression is induced by molecules such as various inflammatory paracrines.

12

nonsteroidal anti-inflammatory drugs (NSAIDS)

The familiar and widely used _______________________, such as aspirin, ibuprofen, and naproxen, are inhibitors of cyclooxygenase

13

Glucocorticoids

_______________, which are often used as powerful anti-inflammatory drugs, repress the expression of COX2.

14

COX1 and COX2

The most common NSAIDS, such as aspirin, ibuprofen, and naproxen, inhibit both ________ & _________.

15

COX2

More recent (and expensive) drugs, such as celecoxib, selectively act on just ________ . These are prescribed to selectively counter inflammation without stimulating the secretion of stomach acid.

16

covalently modifies

Aspirin is interesting in that it ____________ ____________COX, and thus new enzyme must be synthesized to replace that blocked.

17

synthesis of new platelets

As aspirin is being absorbed, platelets moving through the intestines have their COX permanently blocked. Since platelets lack a nucleus, new COX forms only with the ____________________________.

18

linoleic in our diet, its found on the phospholipid molecule in the membrane

What molecule is the source of arachidonic acid and where is it found?

19

phospholipase A2 (PLA₂)

Name the enzyme that, when activated, releases arachidonic acid?

20

lipooxygenase

What enyzme acts on arachidonic acid and begins the process through which leukotrienes are formed?

21

cyclooxygenase2 (COX2)

Name a specific enzyme that acts on arachidonic acid and that is induced by inflammatory paracrines.

22

celecoxib, acetaminophen

Name a drug that does not tend to block COX1 in the stomach.

23

Aspirin

Name a drug that covalently binds to COX.