CHAPTER
Enzymes II: Regulation
The metabolic rate of key substances, which can proceed
in multiple pathways, is regulated and integrated. A close
interrelationship exists among products formed by differ-
ent metabolic pathways from a common metabolite. For
example, glucose can be consumed either by oxidation
to CO
2
or by conversion to glycogen, lipid, nonessential
amino acids, or other sugar molecules. The glucose supply
of the body can be derived either from the diet or from the
breakdown of glycogen, a polymer of glucose (primarily
from the liver and the kidney), or it can be synthesized
from some amino acids or lactate (predominantly in the
liver). These processes of glucose utilization and synthe-
sis are under tight regulation. In fact, the plasma glucose
level is maintained at the level at which tissues (e.g., brain,
erythrocytes, kidney medulla, and the lens and cornea of
the eye) that require glucose as a primary substrate are
not deprived of this essential fuel. Each of these metabolic
pathways is mediated by enzymes that are unique for a
given pathway and that are under control. Metabolic path-
ways do not usually compete with each other for utilization
of a substrate, and they operate only to serve a particular
physiological need or function.
7.1 Types of Regulation
A metabolic pathway involves many enzymes functioning
in a sequential manner or in some unique arrangement to
carry out a particular metabolic process. Control of a path-
way is accomplished through modulation of the activity of
only one or a few key enzymes. These
regulatory enzymes
usually catalyze the first or an early reaction in a metabolic
sequence. A regulatory enzyme catalyzes a
rate-limiting
(or rate-determining) chemical reaction that controls the
overall pathway. It may also catalyze a chemical reac-
tion unique to that pathway, which is known as a
com-
mitted step.
In the metabolic pathway for the formation of
E from A,
B
El
£ 3
D
£ 4
the conversion of A to B, catalyzed by the enzyme Ei, is
the rate-limiting step and also a committed step. The rate-
limiting step need not be the same as the committed step.
In the branched metabolic pathway,
E
if the conversion of A to B is the rate-limiting step, the
committed step in the pathway for the formation of N is
the conversion of B to L (B —> L), catalyzed by the en-
zyme E
5
. Those enzymes which catalyze the rate-limiting
step or the committed step of a pathway are under reg-
ulation. When the end product exceeds the steady-state
level concentration, it inhibits the regulatory enzyme in an
109
