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