Metabolism of Carbolrydrates
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I MetabolismofCarbolrydrates HO-C-H I H-C-OH I HO*C-H I H-C-OH I h-u I cH2-oH Glucose energy Major pathways f arbohydratesare the major sourceof t \.-for the living cells.As such,carbohydrates of carbohydrate metabolism are the firstcellular constituents, synthesized by The important pathways of carbohydrate green plantsduring photosynthesisfrom carbon metabolismare listed dioxide and water, on absorptionof light. Thus, (Embden-Meyerhofpathway) : { light is the ultimate source of energy for all 1. Glycolysis I biologicalprocesses. The oxidationof glucoseto pyruvateand lactate. I The monosaccharide glucose is the central 2. Citric acid cycle (Krebs cycle or molecule in carbohydrate metabolism since all tricarboxylicacid cycle) : The oxidationof acetyl the major pathwaysof carbohydratemetabolism CoA to CO2. Krebs cycle is the final common are connected with it (Fig.l3,1). Clucose is oxidative pathway for carbohydrates,fats or utilizedas a sourceof energy,it is synthesized amino acids, through acetYlCoA. from non-carbohydrateprecursors and storedas : The synthesis of glycogen to releaseglucose as and when the 3. Gluconeogenesis glucosefrom non-carbohydrateprecursors (e.9. need arises. The other monosaccharides glyceroletc.). important in carbohydrate metabolism are amino acids, fructose,galactose and mannose. 4. Glycogenesis: The formation of glycogen The fasting blood glucose level in normal from glucose. individualsis 70-100 mg/dl (+.5-5.5mmol/l) and 5. Glycogenolysis : The breakdown of is very efficientlymaintained at this level (for it glycogento glucose. details reler Chapter 35). Liver plays a key role in monitoring and stabilizing blood glucose 6. Hexose monophosphate shunt (pentose fevels. Thus liver may be appropriately phosphatepathway or directoxidative pathway) : considered as glucostat monitor. This pathway is an alternativeto glycolysisand Chapter 13: METABOLISMOF CABBOHYDRATES 245 OXDATIVE PATHWAYS SYNTHETIC PATHWAYS 2. Insulin-dependenttransport system : This occurs in muscle and adiposetissue. Othercarbohydrates Glycolysis (galactose,fructose) Glucose transporters : In recent years,at least six glucosetransporters (CLUT-l to CLUT-5 and Glycogenesis Hexosemono- CLUT-7) in the cell membranes have been phosphateshunt identified. They Lipogenesis exhibit tissue specificity. For synthesisof fat) instance,CLUT-I is abundant in erythrocytes whereas Uronicacid Non-essential GLUT-4 is abundant in skeletalmuscle pathway aminoacids and adiposetissue. Insulin increasesthe number and oromotes Flg. 13.1: Overuiewof glucosemetabolism. the activitv of CLUT-4 in skeletalmuscle and (Note : For majoity of the pathways, glucose adipose tissue. In type 2 diabetes mellitus, insulin resistanceis observed in these tissues. This is due to the reduction in the quantity of CLUT-4 in insulindeficiency. TCA cyclefor the oxidationof glucose(directly to carbon dioxide and water). Z. Uronic acid pathway : Clucose is convertedto glucuronic acid, pentosesand, in someanimals, to ascorbicacid (notin man).This pathwayis also an alternativeoxidative pathway Clycolysis is derived from the Creek words (glycose-sweet for glucose. or sugar;lysis-dissolution). lt is a universal pathway in the living cells. The 8. Galactose metabolism : The pathways complete pathway of glycolysiswas elucidated concernedwith the conversionof galactoseto in 1940. This pathway is often referred to as glucoseand the synthesisof lactose. Embden-Meyerhof pathway (E.M, pathway) in 9. Fructose metabolism : The oxidation of honour of the two biochemistswho made a fructose to pyruvate and the relation between major contribution to the knowledge of glycolysis. fructoseand glucosemetabolism. Glycolysis 10. Amino sugar and mu.opotyr"ccharide is defined as the sequence of reactions (or metabolism: The synthesisof amino sugarsand converting glucose glycogen) to pyruvate other sugars for the formation of mucopoly- or lactate, with the production of ATP. saccharidesand glycoproteins. Salient features Entry of glucose into cells 1. Clycolysistakes place in all cells of the body. The enzymes of this pathway are present Clucoseconcentration is very low in the cells in the closomal fraction of the cell. comparedto plasma (for humans< 100 mg/dl). However, glucose does not enter the cells by 2. Clycolysisoccurs in the absenceof oxygen simple diffusion.Two specifictransport systems (anaerobic) or in the presence of oxygen are recognizedfor the entry of glucoseinto the (aerobic). Lactate is the end product under cells anaerobic condition. In the aerobic condition, .l pyruvate is formed, which is then oxidized to . Insulin-independent transport system of CO2 and H2O. glucose : This is a carrier mediated uptake of glucosewhich is not dependenton the hormone 3. Clycolysis is a major pathway for ATP insulin.This is operativein hepatocytes,erythro- synthesisin tissues lacking mitochondria, e.g. cltes and brain. erythrocytes,cornea, lens etc. 246 BIOCHEMISTFIY 4. Clycofysis is very essentialfor brainwhich acts only at higher levels of glucose is dependenton glucosefor energy.The glucose i.e., after a meal when blood glucose in brain has to undergo glycolysisbefore it is concentrationis above 100 mg/dl. oxidized to CO2 and H2O. Glucose i-phosphate is impermeable 5. Clycolysis(anaerobic) may be summarized to the cell membrane. lt is a central by the net reaction molecule with a variety of metabolic glycogenesis,gluco- Clucose + 2ADP + 2Pi ------+2lactate + 2ATP fates-glycolysis, neogenesis and pentose phpsphate pathway 6. Clycolysisis a central metabolic pathway. with many of its intermediatesproviding branch point to other pathways.Thus, the intermediates 2. Clucose6-phosphate undergoes isome- give in of glycolysisare usefulfor the synthesisof amino rization to fructose 6-phosphate phospho- acids and fat. the presenceof the enzyme hexosdisomerase and Mg2*. 7. Reversal of glycolysis along with the alternate arrangements at the irreversible 3. Fructose6-phosphate is phosphorylated steps, will result in the synthesisof glucose to fructose1,6-bisphosphate by phospho- (gluconeogenesis). fructokinase(PFK). This is an irreversible and a regulatorystep in glycolysis. Reactions of glycolysis B. Splitting phase The sequence of reactions of glycolysis is 4. The six carbon fructose 1,6- given in Fig.l3.2. The pathway can be divided bisphosphateis split (hencethe name into three distinct phases glycolysis) to two three-carbon A. Energyinvestment phase or priming stage compounds, glyceraldehyde 3-phos- B. Splittingphase phate and di hydroxyacetonephosphate by the enzyme aldolase(fructose 1,6- C. Energygeneration phase. bisphosphatealdolase). The sequence of reactions are discussed 5. The enzyme phosphotrioseisomerase below. catalysesthe reversibleinterconversion A. Energy investment phase of glyceraldehyde 3-phosphate and 1. Glucose is phosphorylatedto glucose dihydroxyacetone phosphate. Thus, 6-phosphate by hexokinase or tvvo molecules of glyceraldehyde glucokinase (both are isoenzymes). 3-phosphate are obtained from one This is an irreversible reaction, moleculeof glucose. dependent on ATP and Mg2+. The C. Energy generation phase enzymehexokinase is presentin almost 6. Glyceraldehyde3-phosphate dehydro- all the tissues. lt catalyses the genase converts glyceraldehyde phosphorylation of various hexoses 3-phosphateto 1,3-bisphosphoglycerate. (fructose, mannose etc.), has low K,.n This stepis importantas it is involvedin for substrates(about 0.1 mM) and is the formationof NADH + H+ and a high inhibited by glucose6-phosphate. energy compound 1,3-bisphospho- Clucokinasepresent in liver, catalyses gfycerate. lodoacetate and arsenate the phosphorylationof only glucose, inhibit the enzyme glyceraldehyde has high K. for glucose(10 mM) and is 3-phosphatedehydrogenase. ln aerobic not inhibited by glucose6-phosphate. condition, NADH passesthrough the Due to high affinity (low K.), glucose electron transport chain and 6 ATP is utilized by hexokinaseeven at low (2 x 3 ATP)are synthesizedby oxidative concentration, whereas glucokinase phosphorylation. *irapEer "?*8: METABOLISMOF CARBOHYDBATES 247 HO-C\ H-c-oH I HO-C-H O H-J-oHI tl H-C ' Phosphotriose H-C:O ?H'-o-(P isomerase I 6nr-or-r H-C-OH Glucose F=o cH20H cHr-o-@ Dihydroxyacetone . Glyceraldehye phosphate I 3-phosphate Pi. NAD* NADH+ H ? ?-o-<z H_C_OH cnr-o-@ Glucose G-phosphate 1,3-Bisphosphoglycerate t ADP.I I Phosphohexose Fomerase M1 J cH2oH ATPI ?-or , coo- Ho-c-H H-C-OH I H-C-OH O 6Hr-o-@ H--C I 3-Phosphoglycerate Cur-o-@ I Fructose 6-phosphate J coo- H-E-o-O Phosohofructokinase t- cH2-oH 2-Phosphoglycerate I Mg2* l---,---tsnolase ?H'-o-O Hro4 ?-or j Ho-c-H , I coo- H-C-OH O I J-o-l>v *-C 8*, Jirr-o-@ Phosphoenolpyruvate Fructose 1,6-bisphosphate . ADP- I Mg' I J ATP+ Fig 13.2 contd, next column Fig 13,2 contd, next page 248 E|IOCHEMISTFIY coo- 10. The enzyme pyruvatekinase catalyses I phosphate c-oH the transferof high energy tl from phosphoenol PYruvateto ADR CHe leading to the formation of ATP.This Pyruvate(enol) step also is a substrate level phosphorylation. (Pyruvate kinase I SPontaneous Mn2*.) + t requiresK+ and either Mg2+ or coo- This reaction is irreversible. I C:O I Gonversion of pyruvate to CHg Pyruvate(keto) lactate-signilicance f pyruvate produced in glycolysis NADH+ H-\ The fate of Lacrare presence absenceof oxygen dehydrogenas€ dependson the or NAD++,j + in the cells.Under anaerobic conditions (lack of coo- Oz), pyruvateis reducedby NADH to lactatein I presenceof the enzyme lactatedehydrogenase H-Q-OH I (competitive inhibitor-oxamate). The NADH