Download 24.12 Control of glycogenolysis

24."12Control of Glycogenolysis
755
24.12 Controlof glycogenolysis
AIM: Todescribethe hormonol control of glycogenolysis.
Glucagon and epinephrine
stimulate glycogenolysis.
Recallfrom Section23.7that phosphorylase,an important enzyne catalyst
of glycogenolysis,is converted from an inactive form (phosphorylaseb) to
an active form (phosphorylasea) upon phosphorylation byATP This conversion is subject to hormonal control by glucagon, a peptide hormone.
lVhen levels ofblood glucoseare low glucagonproduced bythe pancreas
entersthe bloodstreamand is carried to its target cells-the primary target
of glucagonis liver cells.Glucagonstimulatesthe production of cAMP (Fig.
24.10),which activatesa protein kinaseby binding to it. The protein kinase
catalyzesthe phosphorylation of phosphorylaseb, producing phosphorylase a. Phosphorylasea then begins to catalyzethe breakdor,rrnof glycogen.
The end result of the action of glucagonis to raisethe level of glucosein the
blood.
Another hormone that stimulates the breakdo'ornof glycogen is epinephrine (adrenaline).Epinephrine is often cailed the "flight or flght" hormone becauseit is secretedby the adrenalglandsin responseto a threat of
bodily harm. The main effect of epinephrine is on muscle cells,which may
need energy to meet the threat. The nervous system is also mobilized
Stimulus
(low blood glucose)
+
Glucagon
F i g u r e2 4 . 1 0
Clucagonpromotesthe
breakdownof glycogen
stored in liver cellsto
glucose.Someof the
glucoseproducedby
livercellsis carriedby
the blood to other
tissues.
Liver cell
Glucose
[enters blood)
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24 Carbohydrates
CHAPTER
simultaneously.Within moments of the releaseof epinephrine, all systems
are go.You may have experienced the unique feeling that results-perhaps
at a crucial point in an athletic contest, in an automobile accident or nearaccident, or by stepping on a snake on a woodland trail.
The path leading from epinephrine production to glycogenolysisin
muscle is similar to the path used in the liver. There is, however, one major
difference. Becausemuscle cells lack the enzyme necessary to hydrolyze
glucose G-phosphateto glucose and glucose 6-phosphate cannot easily
pass through cell membranes, all the glucose 6-phosphate produced by
glycogenolysisin muscle cells is used for glycolysiswithin the muscle.
24.1t Glucoseobsorption
AIMS: To describethe productionond functionof insulin.To
nomethe termsfor low and high sugor levelsin the
blood, To describethe physiologic effectsof low and high
sugar levelsin the blood. To explain the phrose
"storvotionin the midstof plenty" os oPPliedto diobetes.
Insulin stimulates the
absorption of glucose by tissue
cells.
Although all cells degrade glucose, most carbohydrate mdtabolism occurs
in three places in the body: the muscle, the fatty tissue, and the liver. Liver
cells present no barrier to the entry of glucose from the blood. The passage
of blood glucose through the membranes of muscle and fat cells must be
stimulated bythe peptide hormone insulin (Fig.24.11).
Proinsulin, an inactive form of insulin, is synthesized as a single peptide chain in the pancreas. Proinsulin is packaged in granules and converted to active insulin within the granulesby the action of peptidases.The
activation of proinsulin to insulin is very similar to the activation of zymogens to active en4lmes.
Upon releaseinto the bloodstream, insulin initiates a chain of eventsby
which blood glucose is permitted to enter muscle and fat cells (Fig. 24.12).
Achain
Bchain
-
co2H
NHz
-
24.1I
Figure
structure
of human
Theprimary
insulin.
13 ta
co2H
24.13Glucose
Absorption 757
Stimulus
(high glucose concentration in blood)
n
Insulin
Tissue cell
.....i
::=
l : ::-:-:.
.:::.
Figure
24.12
lnsulinstimulates
the uptakeof
glucosebytissuecellsby starting
a process
that eventually
renders
thecellmembranes
permeable
to
glucose.
Thesecondmessenger
for the process
is probablycGMP
ratherthancAMP.
Dseenlers
scientists believe that the second messengerfor insulin is cyclic guanosine
monophosphate lcGMl), a compound similar in structure to cAMp \fhen
glucoseenterstissuecells,the blood glucoseconcentration decreases.The
drop in blood sugar is th.ehypoglycemiceffectofinsulin. A flaw in any rink of
the chain-from the production of insulin to the uptake of glucose by tissues-is a serioushealth problem.
Hypoglycemia
Hlpoglycemia
hypo(Greek): below
glyc: glucose
haima (Greek): blood
Hyperglycemia
hyper(Greek): above
glyc: glucose
haima (Greek): blood
Glycosuria
glyco (Greek): sweet
uria (Greek): urine
and hyperglycemia
A blood glucoselevel between 70 and 90 mg/100 mL of blood is normal.
And it is important that the blood sugar concentration be kept in this range.
People who experience mild hypoglycemia-low
blood sugar-may
become pale, weak, and nervous. Severehypoglycemia, a blood sugar level
of lessthan 20 mg of glucoseper 100 mL of blood, leads to shock, conr,,ulsions, coma, and finally death. There also can be too much of a good thing.
Hyperglycemia-high blood sugar-for a short time is not usually harmful,
but prolonged hyperglycemia is a syrnptom of diabetes mellitus.
Diabetes
mellitus
Diabetes mellitus is afamily of diseasesin which the uptake of btood gtucoseby tissuesis impaired. Blood glucose levels may become so high that
glycosuria-the appearanceof glucosein the urine-begins to occur. Loss
of body water that is needed to eliminate excessglucose can severely
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Glycosuriaoccasionallyoccurs
during pregnancybecauseofhormonal changes.As long as blood
glucoselevelsare normal, this is
usually not a seriouscondition.
dehydrate a patient with untreated diabetes.The name diabetesmellitusliterally means "sweet siphon." Although there is plenty of glucose in the
blood, glucose cannot reach tissueswhere it is urgently needed' Thus these
untreated patients experienceweight loss and constant hunger. This is
nothing more or lessthan starvation in the midst of plenty.
There are many causesof diabetes,not all of which arewell understood'
In type I (insulin-dependent or juvenile-onset) diabetes,which usually
appears in children before age 10, practically no insulin is produced by the
victim's pancreas.Type I diabetes is usually treated by daily injections of
insulin. The insulin dose must be carefully regulated,though; too much
insulin produces insulin shock. Caused by seuerehypoglycemla, insulin
shock bears the potential for corna and death. Diabetics often carry candy
bars to eat if they feel the onset of insulin shock. Type II (non-insulindependent or maturity-onset) diabetics, those in whom q,Tnptoms appear
during young adulthood or middle age, appear to produce insulin but the
releaseis delayed. About 20Toof type II diabetics require insulin. In many
others, releaseof their o'orninsulin can be stimulated by drugs such as
tolbutamide.
H
cH3-cH2-cH2-cHz
HO
llll
-N-C-N-S
lttl
oo
CHs
Tolbutamide
Diabetes has many more effects on metabolism and health than the few
mentioned here.More of theseeffectsare consideredin the next chapter.
The insulin used to treat human diabetics formerly came from rabbits
and cattle. The amino acid sequencesof the insulin of these speciesand
humans are similar enough that no severe allergic response usually
occurred.Today,human insulin is being produced on a commercial scale
by bacteria. A functional gene for the sgrthesis of human insulin was
insertedinto the bacteriaby the gene-splicingmethod describedin Section
20.13.The genetically engineered bacteria are a convenient source of
human insulin for treatment of diabetes.
24.8
EXERCISE
PRACIICE
Insulin is a peptide of 51 amino acid residues.Explain why this hormone cannot be administeredorally to patientswith diabetesbut must
be given intravenously.
sq$tu€3w&ffiY
Glucoseis a major source of energy for living creatures, and some of the reactions by which it is oxidized to carbon dioxide provide a common pathway for the oxidation of fats and amino acids.
Glucoseis oxidized in three stages:(1) oxidation to
pyruvate in glycolysis, (2) formation of acetyl CoA
from pyruvate,and (3) oxidation ofthe acetyl group
of acetyl CoA to carbon dioxide in the citric acid
cycle.
For eachmolecule of glucoseoxidized,the citric
acid cyclealsoproducessixmoleculesof NADH, two
of FADH2,and two of AIP'vVhen oxygen is available,