Page 167 - Color Atlas of Biochemistry
P. 167
158 Metabolism
Regulation Glucocorticoids—mainly cortisol (see
p. 374)—induceall of thekey enzymes in-
volved in gluconeogenesis [4,6,8,9]. At the
A. Regulation of carbohydrate metabolism
same time, they also induce enzymes in-
In all organisms, carbohydrate metabolism is volved in amino acid degradation and thereby
subject to complex regulatory mechanisms provide precursors for gluconeogenesis. Reg-
involving hormones, metabolites, and ulation of the expression of PEP carboxy-
coenzymes. The scheme shown here (still a kinase, a key enzyme in gluconeogenesis, is
simplified one) applies to the liver, which discussed in detail on p. 244.
has central functions in carbohydrate metab- Metabolites. High concentrations of ATP
olism (see p. 306). Some of the control mech- and citrate inhibit glycolysis by allosteric reg-
anisms shown hereare noteffectivein other ulation of phosphofructokinase. ATP also
tissues. inhibits pyruvate kinase. Acetyl-CoA, an inhib-
One of the liver’smost important tasksisto itor of pyruvate kinase, has a similar effect. All
store excess glucose in the form of glycogen of these metabolites arise from glucose
and to release glucose from glycogen when degradation (feedback inhibition). AMP and
required (buffer function). When the glycogen ADP, signals for ATP deficiency, activate gly-
reserves are exhausted, the liver can provide cogen degradation and inhibit gluconeogene-
glucose by de novo synthesis (gluconeogene- sis.
sis; see p. 154). In addition, like all tissues, the
liver breaks glucose down via glycolysis.
These functions have to be coordinated with B. Fructose 2,6-bisphosphate
each other. For example, there is no point in Fructose 2,6-bisphosphate (Fru-2,6-bP) plays
glycolysis and gluconeogenesis taking place an important part in carbohydrate metabo-
simultaneously, and glycogen synthesis and lism. Thismetabolite isformed in small quan-
glycogen degradation should not occur simul- tities from fructose 6-phosphate and has
taneously either. This is ensured by the fact purely regulatory functions. It stimulates gly-
that two different enzymes exist for important colysis by allosteric activation of phospho-
steps in both pathways, each of which cata- fructokinase and inhibits gluconeogenesis by
lyzes only the anabolic or the catabolic reac- inhibition of fructose 1,6-bisphosphatase.
tion. The enzymes are also regulated differ- The synthesis and degradation of Fru-2,6-
ently. Only these key enzymes are shown bP are catalyzed by one and the same protein
here. [10a, 10b]. If the enzyme is present in an un-
Hormones. The hormones that influence phosphorylated form [10a], it acts as a kinase
carbohydrate metabolism include the pepti- and leads to the formation of Fru-2,6-bP. After
des insulin and glucagon; a glucocorticoid, phosphorylation by cAMP-dependent protein
cortisol; and a catecholamine, epinephrine kinase A (PK-A), it acts as a phosphatase [10b]
(see p. 380). Insulin activates glycogen and now catalyzes the degradation of Fru-2,6-
synthase ([1]; see p. 388), and induces several bP to fructose 6-phosphate. The equilibrium
enzymes involved in glycolysis [3, 5, 7]. At the between [10a] and [10b] is regulated by hor-
same time, insulin inhibits the synthesis of mones. Epinephrine and glucagon increase
enzymes involved in gluconeogenesis the cAMP level (see p. 120). As a result of
(repression; [4,6,8,9]). Glucagon, the antag- increased PK-A activity, this reduces the Fru-
onist of insulin, has the opposite effect. It 2,6-bP concentration and inhibits glycolysis,
induces gluconeogenesis enzymes [4, 6, 8, 9] while at the same time activating gluconeo-
and represses pyruvate kinase [7], a key en- genesis. Conversely, via [10a], insulin acti-
zyme of glycolysis. Additional effects of glu- vates the synthesis of Fru-2,6-bP and thus
cagonare based onthe interconversion of en- glycolysis. In addition, insulin also inhibits
zymes and are mediated by the second mes- the action of glucagon by reducing the cAMP
senger cAMP. This inhibits glycogen synthesis level (see p. 120).
[1] and activates glycogenolysis [2].
Epinephrine acts in a similar fashion. The in-
hibition of pyruvate kinase [7] by glucagon is
also due to interconversion.
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
All rights reserved. Usage subject to terms and conditions of license.
