Ttl Ttl O L-O-L-O-I-.-V

744 CHAPTER24 Carbohydratesin LivingOrganisms

24,9 Glucosestoroge

AIM: To describehow excessglucose is tempororily storedin the body.

Foods containing carbohydrates Focus are one source of the glucose used for energy production in the cell. As you have seen, another source of glucose Glucose is stored as glycogen. is gluconeogenesis.Glucose that is not required to meet the immediate energy needs of the body is assembled into glycogen, the animal form of starch; this anabolic processis called glycogenesis. Glycogenesisrequires two enzyffres: glycogen synthetase and branching enzyme. Glycogen synthetase promotes the formation of the a(l----+4)glycosidic bonds that form the straight-chainportions of glycogen.As its name implies, the branching en4/rne promotes the formation of a(l.+6) glycosidic linkages at branch points of the bushy glycogen molecule. Glucose adds to an existing glycogen chain only if it is fust activated to uridine diphosphate glucose (UDP-glucose).The starting materials for the activation are glucose1-phosphate and uridine triphosphate (UTp),one of the nucleotide triphosphates used in the synthesis of RNA. The glucose 1- phosphate comes from glucose 6-phosphate by way of the following enzvme-catalvzed reaction:

CH,O-@ CH2OH t-ot- t/' \ \gH / Ho \_JoH o-@ ll OH OH GlucoseG-phosphate Glucose 1-phosphate

The glucose1-phosphate nowreacts with the UTP to form UDp-glucose and inorganic pyrophosphate (P4).

o O

HN,.\ HN,\ ttl ttl oarv/ CH,OH ooo ,[o lttl T\' t/' \r o + o .o- | pp. \qHlil l-o-l-o-i-.-v I o- o- o- .r-lH,o 2D. 4L "oHo-l-o- I oH o- OH OH Glucose 1-phosphate Uridine triphosphate Uridine diphosphate glucose (UDP-glucose) (UTP)

Note that the hydrolysis of the high-energy anhydride bond of the PP; 24.10Glycogen Breakdown 749

releasessubstantial energy and therefore helps drive the formation of the UDP-glucose.Once the UDP-glucoseis formed, its glucoseunit attachesto the end of an existing glycogen chain by an cx(l----+4)linkage.

,tr-u,l1:' F""' / \ o o lUridinel* l/' \ \oH / lt il \gH,/ Hot+o-l-o-l-o HoF_r o* OHOO-OH UDP-glucose Glycogenchain

oo I uridine I iltl o-P-o-P- o oA Figure24.5 o-o Livercell of a rat fed a high-carbo- OH OH hydratediet. The dark areasare Uridine diphosphate (UDP) Glycogenchain plus I new glucoseunit massesof glycogen. No high-energy phosphoric acid anhydride bonds are b-roken in this reaction, so the cell's total investment for each molecule of glucose incorporated into glycogenis two high-energy phosphate bonds-one to make glucose6-phosphate from glucoseand one in the hydrolysis of PP; to 2Pi. A typical runner can call on his or Glycogen is temporarily stored in muscle cells and liver cells until glu- her glycogen reservesto provide cose is needed (Fig. 24.5).The amount of liver glycogenis seldom more glucose for energy for 2 to 3 hours. than 5% of the weight of fresh liver tissue. Muscle glycogen seldom exceeds Once the glycogen reservesare 1% of the weight of fresh muscle. gone, a runner "hits the wall" and is unableto maintain the previous level ofactivity. PRACTICEEXERCISE 24.6 In glycogenesis,the glucose1-phosphate comes from glucose6-phosphate by way of an enzyme-catalyzedreaction. Where does the glucose 6-phosphatecome from?

24.10 Glycogenbreokdown AIM: To distinguish betweenthe body's aseof liver glycogenond muscleglycogen.

lVhen your body's glucosesupply getslow, glycogenis broken dourn to meet energy needs. The process by which glycogen is broken down is called Stored glycogen is degraded to glycogenolysis ("splittingof glycogen'). Glycogenolysisstartswiththe con- meet glucose needs. version of glycogen into glucose l-phosphate. The enzyrne phosphorylase catalyzesthis conversion. 750 CHAPTER24 Carbohydtatesin LivingOrganisms

CH,OH o ,f-q Pi /' \ ttot--f\ori A OH OH OH OH Glycogenchain CH2OH CH2OH )t-o /-o - t1'--\ I/' \ - NOH nnOH n

"oF_ro\-_-J/o*OH GlucoseI-phosphate Glucosechain minus I glucoseunit In the processof cleaving glycogen,a phosphoryl group of inorganic phosphate (4) is transferredto glucose.To enter glycolysis,the glucose1- phosphatemust be convertedto glucose6-phosphate. The catalysisof this reactionis accomplishedby a reversalof the reactionused to make glucose 1-phosphate.

- J=-o ;- /-o,, l/^'' \'/ N*OH KoH ) HoY_!ro-@ HoY_1oH OH OH Grucoser-phosphate %;?::.r#;ii,lJ"

Negativelycharged glucose 6-phosphate cannot readily pass through the membranesof cells.In muscle cells,all the glucose6-phosphate produced by glycogenolysisis used for glycolysis.Liver cells have a broader responsi- bility: They must distribute glucoseto other tissuesvia the blood. There- fore, liver cells, but not muscle cells, contain an enzyrne that catalyzesthe hydrolysisof glucose6-phosphate to glucoseand 8. Glucose6-phosphate + H2O - Glucose* P; The glucose leavesthe liver cells and enters the blood, which deliyers it to tissueswhere it is urgently needed. Stored glycogen does not last ldng. After a Z4-}:'or;r'fast, there is virtually no glycogen left in either the liver or the muscle. In the preceding section we noted that the synthesis of glycogen requires the expenditure of two high-energy phosphate bonds for each molecule of glucose incorporated into glycogen (the equivalent of convert- ing two moleculesof AIP to ADP).Since the aerobiccatabolism of eachglu- cosemolecule produces38 ATPmolecules, a net total of 36 AIP molecules is produced from each glucosemolecule stored as muscle glycogen.Thus glycogen is nearly as good a source of cellular energy as glucose itself. Ath- 24.10 GlycogenBreakdown 751

2ADP Glycogenesis Glycogenolysis 2.,4+t Gluconeogenesis

?$TF.(used) Glycolysis 4*jEF,(produced) 2 NAD+ ?NADH

Citric acid 6 NAD+ rycle 6,NAbt{, (2turns) 2 FAD 2 FADH2 Figute24.5 Themany pathways of glucose metabolism.

letic endeavorsrequire energy.Barbara, the biochemically sawy cross- country coach from the Casein Point earlier in this chapter, would like her athletes to store as much glycogen as possible before a meet. In the Follow- up to the Casein Point, below, we will learn more about this strategy. An overview of the metabolic pathways we have discussedis presented in Figure24.6.

Folrow-upro rHECnse rr Portr: Carbohydrateloading r Athletes, especially those involved in long-distance gen wili be available to meet the glucose nJa" ot running, often try to improve their performances by their muscle cells during the meet. Because these maximizing the amount of stored muscle glycogen. glycogen stores are fairly small and rapidly depleted, The practice of eating large amounts of carbohy- they must be built up within a day or two of the ath- drate-rich foods such as pasta before strenuous letic event. The maximum amount of glycogen that activities is known as carbohydtate loading. By pre- can be stored is different among individuals and is scribing a pasta diet to her team, Barbara, the college determined by genetics, but people can approach cross-country coach, ls attempting to maximize her thelr personal maximum by physical condltioning. runners' stores of muscle glycogen so that the glyco-