262 



UNITY AND DIVERSITY IN BIOCHEMISTRY 



enzymes can act equally well in either direction, but the other two are 

 characteristic of the particular direction in which the reaction is taking 

 place ; this is shown in Fig. 79. 



The first stage of the synthesis is phosphorylation by ATP, hexokinase 

 being the catalyst. It is here that a major expenditure of energy occurs; a 

 pyrophosphate bond (12,000 calories) forms a glucose-6-phosphate bond 

 (3000 cal) and by means of this reaction, which in practice is irreversible, 

 the glucose molecule is activated and prepared for a variety of metabolic 

 sequels. In the case we are considering, under the influence of phospho- 

 glucomutase an equilibrium is established between G — 6 — P and G — 1 — P, 

 in fact this equilibrium is part of the steady state in the cell and varies from 

 one cell to another as the steady state varies. 



In the third stage, two enzymes act simultaneously, phosphorylase and 

 the branching enzyme. The glucose portion of a molecule of glucose- 1- 

 phosphate is added to the terminal glucose residue of a chain, with loss of 

 phosphate. The phosphate on Ci is exchanged for a glucoside linkage with 

 the fourth carbon atom of the terminal glucose residue, with little change in 

 free energy. In this synthesis the two substrates therefore are glycogen 



glycogen + phosphate 

 phosphorylase I phosphorylase 



amylo-(l ,4-*- 1 ,6)-transglucosidase 

 (branching enzyme) 



amlyo-1 ,6-glucosidase 



(unbranching enzyme) 



G— 1— P (+ glucose) 



ATP + glucose 



oxidative 

 phosphorylation 



phosphoglucomutase 

 hexokinase 



phosphoglucomutase 



G — 6 — phosphatase 

 G — 6 — P > glucose + phosphate 



phosphohexose 

 -isomerase 



ADP +P 



\G — 6 — P dehydrogenase 

 \ 

 \ 

 \ 



6 — phosphogluconate 



glycerol >• Fructose — 6 — P 



lactic acid ?==^ pyruvic acid < amino acids 



Fig. 79 (G. Cori) — Synthesis and degradation of glycogen in the liver. 



and glucose -1- phosphate. It is the ratio of the concentrations of inorganic 

 phosphate and glucose- 1 -phosphate which determines the direction of the 

 reaction. Since, at pH 7*0, the equilibrium ratio for the reversible reaction 

 is 3 '2, the synthesis of glycogen will occur if there is more than one mole- 

 cule of glucose- 1 -phosphate for every three molecules of inorganic phos- 

 phate. Hence factors tending to lower the concentration of inorganic 

 phosphate will tend to favour synthesis taking place. When, in the branched 

 structure of the glycogen macromolecule, a side-chain has been formed 



