LECTURE ON BIOLOGICAL CHEMISTRY FOR 2 YEAR STUDENTS OF

MEDICAL FACULTY ( 2005- 2006)

LECTURE 12
THEME: Dig!"i#$ %$& %'!#()"i#$ #* +%('#,-&(%"!. S-$",!i! %$& !)/i""i$g #*
g/-+#g$.
0LAN OF LECTURE
1. Bi#/#gi+%/ (#/ #* +%('#,-&(%"! i$ ", #(g%$i!1.
2. C/%!!i*i+%"i#$ #* +%('#,-&(%"!.
2. Dig!"i#$ #* +%('#,-&(%"!: /#+%/i3%"i#$4 (#/ #* $3-1!.
5. Dig!"i#$ #* +//6/#!.
5. T, 1+,%$i!1 #* 1#$#!%++,%(i&! %'!#()"i#$.
6. Di!"6('%$+! #* +%('#,-&(%"! &ig!"i#$.
7. M"%'#/i!1 #* g/-+#g$:
A. S-$",!i! #* g/-+#g$8
B. S)/i""i$g #* g/-+#g$8
C. T, 1+,%$i!1 #* ,#(1#$! %+"i#$ #$ ", g/-+#g$ !-$",!i! %$&
!)/i""i$g.
9. G/-+#g$ !"#(%g &i!%!!
As the word carbohydrate indicates, these are the compound usually made up of
Carbon, Hydrogen and Oxygen. Sometimes they may also contain itrogen and
Sulphur in their molecules.
Bi#/#gi+%/ (#/ #* +%('#,-&(%"! i$ ", #(g%$i!1
!ithout carbohydrates " life as we #now it would not exist. Carbohydrates are the
most abundant molecules in nature. $hey ha%e a wide range of functions, including&
pro%iding a significant fraction of the energy ' about ()* of all energy+ for most
li%ing cells, they are #ey component of such thing as blood group substances on the
surface of red blood cells, and of receptor molecules on the surfaces of cells, they
ser%e as cell membrane components that mediate some forms of intercellular
communication. Carbohydrates also ser%e as a structural component of many
organisms, including the cell walls of bacteria, the exos#eleton of many insects, and
the fibrous cellulose of plants. Carbohydrates are used for the nucleic acids synthesis.
C/%!!i*i+%"i#$ #* +%('#,-&(%"!
Carbohydrates are di%ided into - ma.or groups&
/+ 0onosaccharides
$hey cannot be hydrolysed into a simpler form. $hey subdi%ided into
a+ According to the number of carbon atoms& trioses, tetroses, pentoses, hexoses,
heptoses.
b+ According to the functional group present& aldoses' contain aldehydic group+
and #etoses'contain #etonic group+
1xamples of monosaccharides & glucose, galactose , fructose.
2+ Oligosaccharides
they yield 2 to /) monosaccharides units on hydrolysis. $he most wide spread are
disaccharides 'consists of 2 monosaccharides units .oined by glycosidic lin#ages+
3or example& lactose, maltose, sucrose.
-+ 4olysaccharides
$hey yield more than /) molecules of monosaccharides on hyrolysis. $hey are
subdi%ided into 2 groups&
a+ homopolysaccharides 5 contain only / type of monosaccharides. 1g. Starch,
dextrins, glycogen, cellulose
b+ heteropolysaccharides 'mucopolysaccharides+ 5 they are di%ided into 2
subgroups & eutral and Acidic 'hyaluronic acid, heparin, chondroitin sulfates+
Dig!"i#$ #* +%('#,-&(%"!: /#+%/i3%"i#$4 (#/ #* $3-1!
3ood is the basic and essential re6uirement of man for his %ery existence. $he food
we eat consists of carbohydrates, proteins, lipids, %itamins and minerals. $he bul# of
food ingested is in a complex macromolecular form 'except %itamins, minerals,
monosaccharides and free amino acids+ which cannot, as such, be absorbed by the
body.
Dig!"i#$ i! a process in%ol%ing the hydrolysis of large and complex organic
molecules of foodstuffs into smaller and preferably water7soluble molecules which
can be easily absorbed by the gastrointestinal tract for utili8ation by the organism.
9igestion of macromolecules also promotes the absorption of fat soluble %itamins
and certain minerals. Coo#ing the food, and mastication 'in the mouth+ significantly
impro%e the digestibility of foodstuffs by the en8ymes.
3rancis Syl%ius, who identified the Syl%ian fissures in brain, recogni8ed the
importance of sali%a and pancreatic .uice in the digestion of carbohydrates. :alenine
in /;<< showed the action of pancreatic .uice on starch. Sali%ary amylase 'old name,
4tyalin+was isolated by 0ailhe in /;<= and pancreatic amylase ' old
name,amylopsin+ by Claude >ernard in /;<?. Coo#ing helps in brea#ing of
glycosidic lin#ages in polysaccharides and thus ma#es the digestion process easier.
$he carbohydrate diet mainly consist of polysaccharides 'starch and glycogen+ and
disaccharides 'sucrose and lactose+. @t also contains indigestible cellulose.
9igestion of carbohydrates in the mouth& sali%ary amylase ' ptyalin+ starts the
digestion of coo#ed starch in the mouth.
>ut %ery little digestion ta#e place in the mouth since the food remains there for a
%ery short period of time ' only about = * +
Starch is decompose into maltose through amylodextrin, erythrodextin, achrodextrin.
4tyalin catalyses the hydrolysis of A7/7< lin#ages of polysaccharides.
9igestion of carbohydrates in the stomach& since the food gets mixed with the gastric
.uice the action of amylase stop due to high acidity. @n stomach we ha%e no special
en8ymes for carbohydrates digestion. Sali%ary A7amylase is inacti%ated by HCB. >ut
before all food with amylase will mix with gastric .uice about -)*7<)* of starch is
hydrolyse.
9igestion of carbohydrates in the small intestines& the pancreatic A7amylase in the
small intestines con%ert starch and glycogen into maltose. $hen maltose, sucrose and
lactose present in the diet are digested by the different disaccharidases into the
following monosaccharides. 9isaccharide maltose is con%erted into 2 glucose
molecules under influence of en8yme maltase. 9isaccharide sucrose is con%erted into
glucose and fructose molecules under influence of en8yme sucrase.
9isaccharide lactose is con%erted into glucose and galactose molecules under
influence of en8yme lactase.
Dig!"i#$ #* +//6/#!
Cellulose is a polymer of C797Dlucose, which in contrast to starch, is oriented with
-CH
2
OH groups alternating abo%e and below the plane of the cellulose molecule thus
producing long, unbranched chains. $he absence of side chains allows cellulose
molecules to lie close together and form rigid structures. Cellulose is the ma.or
structural material of plants. !ood is largely cellulose, and cotton is almost pure
cellulose. Cellulose can be hydroly8ed to its constituent glucose units by
microorganisms that inhabit the digesti%e tract of termites and ruminants. Cellulose
may be modified in the laboratory by treating it with nitric acid 'HO
-
+ to replace all
the hydroxyl groups with nitrate groups '-OO
2
+ to produce cellulose nitrate
'guncotton+ which is an explosi%e component of smo#eless powder.
9igestion of cellulose.
Cellulose is not digested in human gastrointestinal tract due to the absence of
en8yme cellulase. $he final products of carbohydrates digestion will be fructose,
glucose and galactose. @t occurs in large intestines. 1n8yme cellulase 'C7amylase+
which is synthesi8ed by microorganisms 'bacterias+ decomposed cellulose partially to
cellobiose and glucose, which brea#7down with formation of different organic acids
'butaric, lactic+.
>iological role of cellulose.
/+ ta#es place in the %itamin >
/)
, >
/2
, E synthesis in large intestine 'by the
bacterias+.
2+ @t adds bul# to the intestinal contents there by stimulating peristalsis and
elimination of food residues.
1xcess of cellulose may cause diarrhea, %iolation in food digestion and absorption.
9eficiency of cellulose may cause constipation.
3ood products which contain a lot of cellulose& apples, pump#ins, plums, beetroots.
T, 1+,%$i!1 #* 1#$#!%++,%(i&! %'!#()"i#$
$he principal monosaccharides produced by the digestion of carbohydrates are
glucose, fructose and galactose. Of these, glucose accounts for nearly ;)* of the
total monosaccharides.$he absorption of sugars mostly ta#es place in the duodenum
and upper .e.unum of small intestine.
$here exists a considerable %ariation in absorption of different monosaccharides.$he
relati%e rates of absorption of important monosaccharides in comparison with glucose
are gi%en below& glucose7/)), galactose7//), fructose7<-, mannose72), xylose7/=,
arabinose7?. @t is obser%ed that hexoses are more rapidly absorbed than pentoses.
3urther among the monosaccharides galactose is most efficiently absorbed followed
by glucose and fructose. @nsulin has no effect on the absorption of sugars.
0echanism of absorption 9ifferent sugars passes different mechanisms for their
absorption. Dlucose is transported into the intestinal mucosal cells by a carrier
mediated and energy re6uiring process.
Dlucose and a
F
share the same transport system 'symport+.$he concentration of a
F
is higher in the intestinal lumen compared to mucosal cells. a
F
, therefore, mo%es
into the cells along its concentration gradient and simultaneously glucose is
transported into the intestinal cells.$his is mediated by the same carrier system.$hus,
a
F
diffuses into the ell and it drags glucose along with it. $he intestinal a
F

gradient is the immediate energy source for glucose transport. $his energy is
indirectly supplied by A$4 since the reentry of a
F
'againt the concentration gradient+
into the intestinal lumen is an energy 5 re6uiring acti%e process. $he en8yme a
F
7 E
F

A$4ase is in%ol%ed in the transport of sodium in exchange of potassium against the
concentration gradient.$he reabsorption of glucose that occurs in the proximal
con%oluted tubules of #idney is also mediated by sodium and the mechanism is
similar that described.
Once within the mucosal cell, glucose is transported into the capillaries by a facilited
passi%e diffusion.$he maximum rate of glucose absorption is about /2)gGh.
$he mechanism of absorption of galactose is similar to that of glucose. $he inhibitor
phlori8in bloc#s the sodium dependant transport of glucose and galactose.
Absorption of fructose& fructose absorption is relati%ely simple. @t does not re6uire
energy and is independant of sodium transport. 3ructose is transported by facilitated
diffusion mediated by a carrier. @nside the epithelial cell, most of the fructose is
con%erted to glucose.$he latter then enters the circulation.
4entoses are absorbed by a process of simple diffusion.
Di!"6('%$+! #* +%('#,-&(%"! &ig!"i#$
@n general, humans possess an efficient system of carbohydrate digestion and
absorption. Since only the monosaccharides are absorbed, any defect in the acti%ities
of disaccharidases results in the passage of undigested disaccharides into the large
intestine. $he disaccharides draw water from the intestinal mucosa by osmosis and
cause osmotic diarrhea. 3urther, bacterial action of these undigested carbohydrates
leads to flatulence. 9isaccharidases are the intestinal brush border en8ymes. Any
alteration in the mucosa of the small intestine caused by se%ere diarrhea,
malnutrition, intestinal diseases or drug therapy will lead to a temporary ac6uired
deficiency of disaccharidases. $he patients with such disorders are ad%ised to restrict
the consumption of sucrose and lactose. Hereditary disorder with deficiency of
indi%idual disaccharidases in infants and children causes intolerance of specific
disaccharides. L%+"#! i$"#/(%$+: defect in the en8yme lactase 'C7galactosidase+ is
the most common disaccharidase deficiency in humans. @t is estimated that more than
half of the worldHs adult population is affected by lactose intolerance. @t is more
commonly found in Africans 'blac#s+ and Asians compared to 1uropeans.
Surprisingly, according to a recent estimate, about ?)* of the adult Asians are lactase
deficient. $he mechanism of how lactase is lost in adults is not clear. @t is howe%er,
#nown that there is a reduced production of lactase rather than an alteration in
en8yme acti%ity. $he treatment of lactose intolerance is 6uite simple. 1limination of
lactose from the diet 'se%ere restriction of mil# and dairy products+ will sol%e the
problem. Continued consumption of lactose by lactose intolerant indi%iduals causes
typical symptoms of flatulence. S6+(%! &*i+i$+-: the deficiency of the en8yme
sucrase causes intolerance to dietary sucrose. @t is estimated that about /)* of
1s#imos of Dreenland and 2* of orth Americans are affected by this disorder. $he
treatment is to remo%e sucrose from the diet.
T, )(#'/1 #* */%"6/$+:
3latulence is characteri8ed by increased intestinal motility, cramps and irritation.
$his occurs after ingestion of certain carbohydrates and is explained as follows.
$he carbohydrates 'di7, oligo7, and polysaccharides+ not hydrolysed by A7amylase
and other intestinal en8ymes cannot be absorbed. Bactose is not hydrolysed in some
indi%iduals due to the deficiency of lactase. $he di7, and oligosaccharides can be
degraded by the bacteria present in ileum 'lower part of small intestine+ to liberate
monosaccharides. $he latter can be metaboli8ed by the bacteria. 9uring the course of
utili8ation of monosaccharides by the intestinal bacteria, the gases such as hydrogen,
methane and carbon dioxide besides lactate and short chain fatty acids"are
released. $hese compounds cause flatulence.
$he occurrence of flatulence after the ingestion of leguminous seeds 'bengal gram,
redgram, beans, peas, soya bean+ is %ery common. $hey contain
&
se%eral nondigestible oligosaccharides by human

intestinal en8ymes. $hese
compounds are degraded and utilised by intesntinal bacteria causing flatulence.
Iaffinose containing galactose, glucose and fructose is a predominant
oligosaccharide found in leguminous seeds.

S-$",!i! #* g/-+#g$
Dlycogen is the storage form of glucose in animals, as is starch in plants. @t is
stored mostly in li%er '(7;*+ and muscle '/72*+. 9ue to more muscle mass, the
6uantity of glycogen in muscle '2=) g+ is about three times higher than that in the
li%er 'J= g+. $he prime function of li%er glycogen is to maintain the blood glucose
le%els, particularly between meals. Bi%er glycogen stores increase in a well7fed state
which are depleted during fasting. 0uscle glycogen ser%es as a fuel reser%e for the
supply of A$4 during muscle contraction. Structure of glycogen& glycogen is a
homopolysaccharide composed of A 797glucose 'up to /)),))) residues may be
present+. $he glucose units are held together by A 7/, < lin#ages. After ;7/) residues
of glucose, a branch is formed with A 7/, ( glycosidic lin#age. Dlycogen is stored as
granules in the cytosol, where most of the en8ymes of glycogen synthesis and
brea#down are present.
$he synthesis of glycogen from glucose is glycogenesis. Dlycogenesis ta#es place
in the cytosol and re6uires A$4 and K$4, besides glucose.
/. Synthesis of K947glucose & $he en8ymes hexo#inase 'in muscle+ and
gluco#inase 'in li%er+ con%ert glucose to glucose (7phosphate. 4hospho7glucomutase
catalyses the con%ersion of glucose (7phosphate to glucose /7phosphate. Kridine
diphosphate glucose 'K94D+ is synthesi8ed from glucose /7phosphate and K$4 by
K947glucose pyrophosphorylase. 4yrophosphate '44i+ produced in this reaction is
hydrolysed to inorganic phosphate '4i+ by pyrophosphatase. $his will ensure the
optimal synthesis of K94D.
2. Ie6uirement of primer to initiate glycogenesis & A small fragment of pre7
existing glycogen must act as a HprimerH to initiate glycogen synthesis. @t is recently
found that in the absence of glycogen primer, a specific protein"namely
HglycogeninH" can accept glucose from K94D. $he hydroxyl group of the amino
acid tyrosine ot glycogenin is the site at which the initial glucose unit is attached.
$he en8yme glycogen initiator synthase transfers the first molecule of glucose to
glycogenin. $hen glycogenin itself ta#es up a few glucose residues to form a fragment
of primer which ser%es as an acceptor for the rest of the glucose molecules.
-. Dlycogen synthesis by glycogen synthase & glycogen synthase is responsible for the
formation of /, <7glycosidic lin#ages. $his en8yme transfers the glucose from K947
glucose to the non7reducing end of glycogen to form A 7/, < lin#ages. $he K94
released can be con%erted bac# to K$4 by nucleoside diphosphate #inase.
<. 3ormation of branches in glycogen &
Dlycogen synthase can catalyse the synthesis of a linear unbranched molecule with
/, < A7glycosidic lin#ages. Dlycogen, howe%er, is a branched treeli#e structure. $he
formation of branches is brought about by the action of a branching en8yme, namely
glucosyl A 7<7( transferase, 'amylo A /, < "L /, ( transglucosidase+. $his en8yme
transfers a small fragment of fi%e to eight glucose residues from the non7reducing end
of glycogen chain 'by brea#ing A 7/, < lin#ages+ to another glucose residue where it is
lin#ed by A 7/, ( bond. $his leads to the formation of a new non7reducing end,
besides the existing one. Dlycogen is further elongated and branched, respecti%ely,
by the en8ymes glycogen synthase and glucosyl <7( transferase. $he o%erall reaction
of the glycogen synthesis for the addition of each glucose residue is
'Dlucose+
n
F Dlucose F 2 A$4 M 'Dlucose+
nF/
F 2 A94 F 4
i
Of the two A$4 utili8ed, one is re6uired for the phosphorylation of glucose while
the other is needed for con%ersion of K94 to K$4.
S)/i""i$g #* g/-+#g$
$he degradation of stored glycogen in li%er and muscle constitutes glycogenolysis.
$he pathway for the synthesis and degradation of glycogen are not re%ersible. An
independent set of en8ymes present in the cytosol carry out glycogenolysis.
Dlycogen is degraded by brea#ing A 7/, <7 and A 7/, (7glycosidic bonds. /. Action of
glycogen phosphorylase & $he A 7/, < glycosidic bonds 'from the non7reducing
ends+ are clea%ed se6uentially by the en8yme glycogen phosphorylase to yield
glucose /7phosphate. $his process" called phosphorolysis"continues unti@ four
glucose residues remain on either side of branching point 'A 7/, (7glycosidic
lin#+. $he glycogen so formed is #nown as limit dextrin which cannot be further
degraded by phosphorylase. Dlycogen phosphorylase possesses a molecule of
pyridoxal phosphate, co%alently bound to the en8yme. 2. Action of debranching
en8yme & $he branches of glycogen are clea%ed by two en8yme acti%ities present
on a single polypeptide called debranching en8yme, hence it is a bifunctional
en8yme.
Dlycosyl < & < transferase 'oligo A 7/, < 7N /,< glucan transferase+ acti%ity remo%es
a fragment of three or four glucose residues attached at a branch and transfers them
to another chain. Here, one A 7/, <7bond is clea%ed and the same A 7/, < bond is
made, but the places are different.
Amylo A7l, (7glucosidase brea#s the A 7/, ( bond at the branch with a single
glucose residue and releases a free glucose. $he remaining molecule of glycogen is
again a%ailable for the action of phosphorylase and debranching en8yme to repeat the
reactions stated in / and 2.
-. 3ormation of glucose (7phosphate and glucose & $hrough the combined action
of glycogen phosphorylase and debranching en8yme, glucose /7phosphate and free
glucose in ratio of ; & / are produced. Dlucose /7phosphate is con%erted to glucose (7
phosphate by the en8yme phospho7glucomutase. $he fate of glucose (7phosphate
depends on the tissue. $he li%er, #idney and intestine contain the en8yme glucose (7
phosphatase that clea%es glucose (7phosphate to glucose. $his en8yme is absent in
muscle and brain, hence free glucose cannot be produced from glucose (7
phosphate in these tissues. $herefore, li%er is the ma.or glycogen storage organ to
pro%ide glucose into the circulation to be utilised by %arious tissues.
@n the peripheral tissues, glucose (7phosphate produced by glycogenolysis will be
used for glycolysis. @t may be noted that though glucose (7phosphatase is absent in
muscle, some amount of free glucose ';7/)* of glycogen+ is produced in
glycogenolysis due to the action of debranching en8yme 'A7/,(7glucosidase acti%ity+.
Rg6/%"i#$ #* g/-+#g$#!i! %$& g/-+#g$#/-!i!
A good coordination and regulation of glycogen synthesis and its degradation is
essential to maintain the blood glucose le%els. Dlycogenesis and glycogenolysis are,
respecti%ely, controlled by the en8ymes glycogen synthase and glycogen phos7
phorylase. Iegulation of these en8ymes is accomplished by three mechanisms&
/.Allosteric regulation
2.Hormonal regulation
-.@nfluence of calcium.
/. Allosteric regulation of glycogen metabolism & $here are some metabolites
that allosterically regulate the acti%ities of glycogen synthase and glycogen
phosphorylase. $he control is carried out in such a way that glycogen synthesis is
increased when substrate a%ailability and energy le%els are high. On the other hand,
glycogen brea#down is enhanced when glucose concentration and energy le%els
are low. @n a well7fed state, the a%ailability of glucose (7phosphate is high which
allosterically acti%ates glycogen synthase for more glycogen synthesis. On the other
hand, glucose (7phosphate and A$4 allosterically inhibit glycogen phosphorylase.
3ree glucose in li%er also acts as an allosteric inhibitor of glycogen phosphorylase.
2. Hormonal regulation of glycogen metabolism & $he hormones, through a
complex series of reactions, bring about co%alent modification, namely
phosphorylation and dephosphorylation of en8yme proteins which, ultimately control
glycogen synthesis or its degradation. Cyclic A04 'cA04+ is the intracellular second
messenger through which many hormones exert their action. @t is synthesi8ed from
A$4 by the en8yme adenylate cyclase, present on the inner surface of cell
membrane. $he hormones li#e epinephrine and norepinephrine and glucagon 'in
li%er+ acti%ate adenylate cyclase to increase the production of cA04. $he en8yme
phosphodiesterase brea#s down cA04. $he hormone insulin increases the
phosphodiesterase acti%ity in li%er and lowers the cA04 le%els.
Iegulation of glycogen synthesis by cA04 & $he glycogenesis is regulated by
glycogen synthase. $his en8yme exists in two forms"glycogen synthase HaH"
which is not phosphorylated and most acti%e, and, secondly, glycogen synthase
HbH as phosphorylated inacti%e form. Dlycogen synthase HaH can be con%erted to
HbH form 'inacti%e+ by phosophorylation. $he degree of phosphorylation is
proportional to the inacti%e state of en8yme. $he process of phosphorylation is
catalysed by a cA047dependent protein #inase. $he protein #inase phosphorylates
and inacti%ates glycogen synthase by con%erting HaH form to HbH form. $he glycogen
synthase HbH can be con%erted bac# to synthase 'aH by protein phosphatase @.
Iegulation of glycogen degradation by cA04 &
$he hormones li#e epinephrine and glucagon bring about glycogenolysis by their
action on glycogen phosphorylase through cA04 as illustrated in 3ig. /-./J.
Dlycogen phosphorylase exists in two forms, an acti%e 'a' form and inacti%e form
'b'. $he cA04"formed due to hormonal stimulus" acti%ates cA04 dependent
protein #inase. $his acti%e protein #inase phosphorylates inacti%e form of
glycogen phsophorylase #inase to acti%e form. '$he en8yme protein phosphatase
remo%es phosphate and inacti%ates phosphorylase #inase+. $he acti%e phosphorylase
#inase phosphorylates inacti%e glycogen phosphorylase HbH to acti%e glycogen
phosphorylase HaH which degrades glycogen. $he en8yme protein phosphatase @ can
dephosphorylate and con%ert acti%e glycogen phosphorylase Ha
O
to inacti%e HbH form.
-. 1ffect of Ca
2F
ions on glycogenolysis & $he re6uirement for A$4 is
tremendously increased during muscle contraction which is met from the glycogen
stores in muscle. !hen the muscle contracts, Ca
2F
ions are released from the
sarcoplasmic reticulum. Ca
2F
binds to calmodulin and directly acti%ates
phosphorylase #inase without the in%ol%ement of cA047dependent protein
#inase. Calmodulin or calcium modulating protein 'mol. wt. /J,)))+ is a protein
which is similar to one of the subunits 'C subunits+ of glycogen phosphorylase
#inase 'with A CP subunits+. 0ost of the action of Ca
2F
related to ner%e conduction
and muscle contraction are mediated through Ca
2F
binding to calmodulin.
@n the muscle, it has been reported that when A$4 is depleted, A04 'note & not
cA04+ directly acti%ates glycogen phosphorylase HbH without phosphorylation.
$he o%erall effect of hormones in glycogen metabolism is that an ele%ated
glucagon or epinephrine le%el increases glycogen degradation whereas an ele%ated
insulin results in increased glycogen synthesis.
G/-+#g$ S"#(%g Di!%!!
Since glycogen molecules can become enormously large, an inability to degrade
glycogen can cause cells to become pathologically engorged, it can also lead to the
functional loss of glycogen as a source of cell energy and as a blood glucose buffer.
Although glycogen storage diseases are 6uite rare, their effects can be most dramatic.
$he debilitating effect of many glycogen storage diseases depends on the se%erity of
the mutation causing the deficiency. @n addition, although the glycogen storage
diseases are attributed to specific en8yme deficiencies, other e%ents can cause the
same characteristic symptoms. 3or example, $ype @ glycogen storage disease '%on
Dier#eHs disease+ is attributed to lac# of glucose7(7phosphatase. Howe%er, this
en8yme is locali8ed on the cisternal surface of the endoplasmic reticulum '1I+, in
order to gain access to the phosphatase, glucose7(7phosphate must pass through a
specific translocase in the 1I membrane. 0utation of either the phosphatase or the
translocase ma#es transfer of li%er glycogen to the blood a %ery limited process.
$hus, mutation of either gene leads to symptoms associated with %on Dier#eHs
disease, which occurs at a rate of about / in 2)),))) people.
Se%eral glycogenoses are the result of deficiencies in en8ymes of glycolysis
whose symptoms and signs are similar to those seen in type : glycogen storage
disease. $hese include deficiencies in muscle phosphglycerate #inase and muscle
pyru%ate #inase as well as deficiencies in fructose /,(7bisphosphatase, lactate
dehydrogenase and phosphoglycerate mutase.
T%'/ #* G/-+#g$ S"#(%g Di!%!!
T-): N%1
E$3-1
A**+"&
0(i1%(-
O(g%$
M%$i*!"%"i#$!
$ype )
glycogen
synthase
li%er
hypoglycemia, early death,
hyper#etonia
$ype @a&
%on Dier#eHs
glucose7(7
phosphatase
li%er
hepatomegaly, #idney
failure, thrombocyte
dysfunction
$ype @b
microsomal
glucose7(7
phosphate
translocase
li%er
li#e @a, also neutropenia,
bacterial infections
$ype @c microsomal 4
i
li%er li#e @a
transporter
$ype @@&
4ompeHs
lysosomal A
7/,<7glucosidase,
lysosomal acid A
7glucosidase
acid maltase
s#eletal and
cardiac
muscle
infantile form Q death by 2,
.u%enile form Q myopathy,
adult form Q muscular
dystrophy7li#e
$ype @@@a&
CoriHs or
3orbeHs
li%er and muscle
debranching
en8yme
li%er, s#eletal
and cardiac
muscle
infant hepatomegaly,
myopathy
$ype @@@b
li%er debranching
en8yme
normal muscle
en8yme
li%er, s#eletal
and cardiac
muscle
li%er symptoms same as type
@@@a
$ype @:&
AndersonHs
branching
en8yme
li%er, muscle
hepatosplenomegaly,
cirrhosis
$ype :&
0cArdleHs
muscle
phosphorylase
s#eletal
muscle
excercise7induced cramps
and pain, myoglobinuria
$ype :@&
HerHs
li%er
phosphorylase
li%er
hepatomegaly, mild
hypoglycemia,
hyperlipidemia and #etosis,
impro%ement with age
$ype :@@&
$aruiHs
muscle 43E7/
muscle,
I>CHs
li#e :, also hemolytic
anemia
$ype :@a,
:@@@ or $ype
@R
phosphorylase
#inase
li%er,
leu#ocytes,
muscle
li#e :@
$ype R@&
3anconi7
>ic#el
glucose
transporter72
'DBK$72+
li%er
failure to thri%e,
hepatomegaly, ric#ets,
proximal renal tubular
dysfunction
R*($+!.
/. Sohn !. Suttie. @ntroduction to >iochemistry. 5 ew Tor#& Holt, Iinehart and
!inston, @nc., /??2.7 -(< p.
2. Sohn 0c 0urry, 0ary 1. Castellion. Deneral, Organic and >iological Chemistry.7
ew Sersy& 4rentice Hall, /??2.7 J(< p.
-. Iobert E. 0urray, 9aryl E. Dranner. HarperUs illustrated >iochemistry. 5 @ndia&
@nternational 1ducation, 2))-.7 (?- p.
4repared by @nna Erynyts#a
Ie%ised
Adopted at the Chair Sitting /J.)(.)=
0inutes V /2