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Limiting Factors for Glycogen Storage in Tumors

I. Limiting Enzymes^*

Vijai N. Nigam, Helen L. MacDonald and A. Cantero

( Montreal Cancer Institute, Research Laboratories, Notre Dame Hospital and Université de Montreal, Montreal, Canada)

The paper presents a study of various enzymes involved in the final accumulation of glycogen in tumor tissues. The solid tumors used are: Novikoff hepatoma, Walker 256 carcinosarcoma, Sarcoma 37, leukemia, and melanoma. It was observed that tumor tissues showed lower activity of phosphoglucomutase and glycogen synthetase as compared with that of normal liver and muscle. All tumors studied except melanoma also showed decreased UDPG¹ pyrophosphorylase levels. Activities for ATP- and UTP-regenerating enzymes—namely, pyruvate kinase and nucleoside disphosphokinase—in tumors were close to those found in normal tissues, thus providing sufficient quantities of cofactors (ATP and UTP) and energy for the polymerization process. UDPG was not diverted to UDPGA in tumors because of the absence of UDPG dehydrogenase. The lesion could be best described as a defective system for glycogen synthesis, owing to low activities of the enzymes involved in the synthetic process (phosphoglucomutase and glycogen synthetase) which were unable to accomplish efficient transformation of G-6-P to G-1-P and of UDPG to glycogen, in the presence of competing high rates of tumor glycolysis and normal polysaccharide degradation by phosphorylase.

^* This work was supported by grants from the National Cancer Institute of Canada.

Presented at the meeting of American Society of Biological Chemists in Atlantic City, April 10, 1961.

¹ The abbreviations used are: AMP, adenosine monophosphate; ADP, adenosine diphosphate; ATP, adenosine triphosphate; UDP, uridine diphosphate; UTP, uridine triphosphate; UDPG, uridine diphosphate glucose; UDPGA, uridine diphosphate glucuronic acid; G-1-P, glucose-1-phosphate; G-6-P, glucose-6-phosphate; DPN, diphosphopyridine nucleotide; TPN, triphosphopyridine nucleotide; GDP, guanosine diphosphate; CDP, cytidine diphosphate; IDP, inosine diphosphate.

Technical assistant.

Received 5/22/61.