Page 123 - Color Atlas of Biochemistry

P. 123

114 Metabolism

Regulatory mechanisms Interconversion processes in most cases
involve ATP-dependent phosphorylation of
theenzymeprotein by a protein kinase or
A. Fundamental mechanisms of metabolic
dephosphorylation of it by a protein phospha-
regulation
tase (see p. 120). The phosphorylated form of
The activities of all metabolic pathways are thekey enzyme is usually themoreactive
subject to precise regulation in order to adjust one, but the reverse may also occur.
the synthesis and degradation of metabolites Modulation by ligands. An important vari-
to physiological requirements. An overview of able that regulates flow through a metabolic
the regulatory mechanisms is presented here. pathway is precursor availability (metabolite
Further details are shown on pp. 116ff. A in the case shown here). The availability of
Metabolite flow along a metabolic pathway precursor A increases along with the activity
is mainly determined by the activities of the of the metabolic pathways that form A (3)and
enzymes involved (see p. 88). To regulate the it decreases with increasing activity of other
pathway, it is suf cient to change the activity pathways that also consume A (4). Transport
of the enzyme that catalyzes the slowest step from one cell compartment to another can
in the reaction chain. Most metabolic path- also restrict the availability of A.
ways have key enzymes of this type on which Coenzyme availability can also often have a
the regulatory mechanisms operate. The ac- limiting effect (5). If thecoenzymeis regen-
tivity of key enzymes is regulated at three erated by a second, independent metabolic
independent levels: pathway, the speed of the second pathway
Transcriptional control. Here, Biosynthesis can limit that of the first one. For example,
of the enzyme protein is influenced at the glycolysis and the tricarboxylic acid cycle are
genetic level (1). Interventions in enzyme mainly regulated by the availability of NAD +
+
synthesis mainly affect synthesis of the cor- (see p. 146). Since NAD is regenerated by the
responding mRNA—i. e., transcription of the respiratory chain, the latter indirectly con-
gene coding for the enzyme. The term “tran- trols the breakdown of glucose and fatty acids
scriptional control” is therefore used (see (respiratory control, see p. 144).
pp. 118, 244). This mechanism is mediated by Finally, the activity of key enzymes can be
regulatory proteins (transcription factors) that regulated by ligands (substrates, products,
act directly on DNA. The genes have a special coenzymes, or other effectors), which as allo-
regulatory segment for this purpose, known steric effectors do notbindatthe active center
as the promoter region, which contains bind- itself, but at another site in the enzyme,
ing sites (control elements) for regulatory thereby modulating enzyme activity (6;see
proteins. The activity of these proteins is, in p. 116). Key enzymes are often inhibited by
turn, affected by metabolites or hormones. immediate reaction products, by end prod-
When synthesis of a protein is increased by ucts of the reaction chain concerned (“feed-
transcriptional control, the process is referred back” inhibition), or by metabolites from com-
to as induction; when it is reduced or sup- pletely different metabolic pathways. The
pressed, it is referred to as repression.Induc- precursors for a reaction chain can stimulate
tion and repression processes take some time their own utilization through enzyme activa-
and are therefore not immediately effective. tion.
Interconversion of key enzymes (2)takes
effect considerably faster than transcriptional
control. In this case, the enzyme is already
present at its site of effect, but it is initially
still inactive. It is only when needed that it is
converted into the catalytically active form,
after signaling and mediation from second
messengers (see p. 120) through an activating
enzyme (E 1 ). If the metabolic pathway is no
longer required, an inactivating enzyme (E 2 )
returns the key enzyme to its inactive resting
state.

118 119 120 121 122 123 124 125 126 127 128