Page 129 - Color Atlas of Biochemistry

120 Metabolism

Hormonal control glycogen breakdown, releasing glucose, and
at the same time inhibits glycogen synthesis.
In higher organisms, metabolic and other Glucagon binds to receptors in the plasma
processes (growth, differentiation, control of membrane (bottom left) and, with mediation
the internal environment) are controlled by by a G-protein (see p. 386), activates the
hormones (see pp. 370ff.) enzyme adenylate cyclase, which forms the
second messenger 3,5 -cyclo-AMP (cAMP)
from ATP. cAMP binds to another enzyme,
A. Principles of hormone action
protein kinase A (PK-A), and activates it.
Depending on the type of hormone, hormone PK-A has several points of attack. Through
signals are transmitted to the target cells in phosphorylation, it converts the active form
different ways. Apolar (lipophilic) hormones of glycogen synthase into the inactive form,
penetrate the cell and act in the cell nucleus, thereby terminating the synthesis of glyco-
while polar (hydrophilic) hormones act on the gen. Secondly, it activates another protein
external cell membrane. kinase (not shown), which ultimately con-
Lipophilic hormones, which include the verts the inactive form of glycogen phosphor-
steroid hormones, thyroxine, and retinoic ylase into the active form through phosphor-
acid, bind to a specific receptor protein inside ylation.Theactive phosphorylase releases glu-
their target cells. The complex formed by the cose 1-phosphate from glycogen, which after
hormone and the receptor then influences conversion into glucose 6-phosphate supplies
transcription of specific genes in the cell nu- free glucose. In addition, via an inhibitor (I) of
cleus (seepp. 118, 244). Thegroup of hydro- protein phosphatase (PP), active PK-A inhibits
philic hormones (see p. 380) consists of hor- inactivation of glycogenphosphorylase. When
mones derived from amino acids, as well as the cAMP level falls again, phosphoprotein
peptide hormones and proteohormones. phosphatases become active, which dephos-
Their receptors are located in the plasma phorylate the various phosphoproteins in the
membrane. Binding of the hormone to this cascade described, and thereby arrest glyco-
type of receptor triggers a signal that is trans- gen breakdown and re-start glycogen synthe-
mitted to the interior of the cell, where it sis. Activation and inactivation of proteins
controls the processes that allow the hor- through phosphorylation or dephosphoryla-
mone signal to take effect (signal transduc- tion is referred to as interconversion.
tion; see pp. 384ff.) In contrast to glucagon, the peptide
hormone insulin (see p. 76) increases glyco-
gen synthesis and inhibits glycogen break-
B. Hormonal regulation of glucose
down. Via several intermediates, it inhibits
metabolism in the liver
protein kinase GSK-3 (bottom right; for de-
The liver plays a major role in glucose homeo- tails, see p. 388) and thereby prevents inacti-
stasis in the organism (see p. 310). If glucose vation of glycogen synthase. In addition, in-
deficiency arises, the liver releases glucose sulin reduces the cAMP level by activating
into the blood, and when blood sugar levels cAMP phosphodiesterase (PDE).
are high, it takes glucose up from the blood Regulation by transcriptional control (top).
and converts it into different metabolites. If the liver’s glycogen reserves have been ex-
Several hormones from both groups are in- hausted, the steroid hormone cortisol main-
volved in controlling these processes. A very tains glucose release by initiating the conver-
simplified versionofthe way inwhich they sion of amino acids into glucose (gluconeo-
work is presented here. Glycogen is the form genesis; see p. 154). In the cell nucleus, the
in which glucose is stored in the liver and complex of cortisol and its receptor (see
muscles. The rate of glycogen synthesis is p. 378) binds to the promoter regions of var-
determined by glycogen synthase (bottom ious key enzymes of gluconeogenesis and
right), while its breakdown is catalyzed by leads to their transcription. The active en-
glycogen phosphorylase (bottom left). zymes are produced through translation of
Regulation by interconversion (bottom). If the mRNA formed. Control of the transcrip-
theblood glucoselevel falls, thepeptide tion of the gluconeogenesis enzyme PEP car-
hormone glucagon is released. This activates boxykinase is discussed on p. 244.

Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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