MCQ2
An adult patient presents with the sudden onset of massive diarrhea.
Grossly, this individual’s stool has the appearance of “rice-water” because of
the presence of flecks of mucus. Cultures of this patient’s stool grow Vibrio
cholerae, a curved, gram-negative rod that secretes an enterotoxin consisting
of a toxic A subunit and a binding B subunit. The cholera enterotoxin
causes massive diarrhea by
a. Inhibiting the conversion of Gi-GDP to Gi-GTP
b. Inhibiting the conversion of Gs-GTP to Gs-GDP
c. Stimulating the conversion of Gi-GDP to Gi-GTP
d. Stimulating the conversion of Gs-GDP to Gs-GTP
e. Stimulating the conversion of Gs-GTP to Gs-GDP
AnswerThe answer is b. (Alberts, pp 734–749. Cotran, pp 92–93, 343–344.)
Many extracellular substances cause intracellular actions via secondmessenger
systems. These second messengers may bind to receptors that
are located either on the surface of the cell or within the cell itself. Substances
that react with intracellular receptors are lipid-soluble (lipophilic)
molecules that can pass through the lipid plasma membrane. Examples of
these lipophilic substances include thyroid hormones, steroid hormones,
and the fat-soluble vitamins A and D. Once inside the cell these substances
generally travel to the nucleus and bind to the hormone response element
(HRE) of DNA.
Some substances that react with cell surface receptors bind to guaninenucleotide
regulatory proteins. These proteins, called G proteins, may be
classified into four categories, namely Gs, Gi, Gt, and Gq. Two of these
receptors, Gs and Gi, regulate the intracellular concentration of cyclic
adenosine 5′-monophosphate (cAMP). In contrast, Gt regulates the intracytoplasmic
levels of cyclic guanosine 5′-monophosphate (cGMP), and Gq
regulates the intracytoplasmic levels of calcium ions. Gs and Gi regulate
intracellular cAMP levels by their actions on adenyl cyclase, an enzyme
located on the inner surface of the plasma membrane that catalyzes the formation
of cAMP from ATP. The adenylate cyclase G protein complex is
composed of the following components: the receptor, the catalytic enzyme
(i.e., adenyl cyclase), and a coupling unit. The coupling unit consists of
GTP-dependent regulatory proteins (G proteins), which may either be
stimulatory (Gs) or inhibitory (Gi). When bound to GTP and active, Gs
stimulates adenyl cyclase and increases cAMP levels. (Gs can be thought of
as the “on switch.”) In contrast, when bound to GTP and active, Gi inhibits
adenyl cyclase and decreases cAMP levels. (Gi can be thought of as the “off
switch.”) It is important to note that cholera toxin and pertussis toxin both
act by altering this adenyl cyclase pathway. Cholera toxin inhibits the conversion
of Gs-GTP to Gs-GDP. In contrast, pertussis toxin inhibits the activation
of Gi-GDP to Gi-GTP. Therefore, both cholera toxin and pertussis
toxin prolong the functioning of adenyl cyclase and therefore increase
intracellular cAMP, but their mechanisms are different. Cholera toxin keeps
the “on switch” in the “on” position, while pertussis toxin keeps the “off
switch” in the “off” position.
