INHIBITION BY MACROIONS 463 



tible to macroanions. A striking difference was demonstrated by Nishitnura 

 (1960), bovine ribonuclease being readily inhibited by polyvinyl sulfate to 

 which Bacillus subtilis ribonucleases are completely resistant. 



Lipoprotein Lipase 



Macroions inhibit lipoprotein lipase but affect other lipases little or not 

 at all. The enzyme from chicken fat is inhibited by macrocations in a purely 

 noncompetitive fashion and the inhibition is rapidly reversible either by 

 dialysis or the addition of a macroanion (Korn, 1962). Poly-L-lysines of 

 increasing chain length are progressively more effective, which is one of the 

 few observations relating polymer size to inhibition. The degree of inhibition 

 by various copolymers of tyrosine and lysine depends on the content of 

 lysine, indicating purely electrostatic binding. The enzyme is also inhibited 

 by macroanions, which may act noncompetitively or competitively (e.g., 

 heparin and polyglucose sulfate). The lipoprotein from mouse heart is inhi- 

 bited by many polysaccharide sulfates as long as there is at least 0.6 sulfate 

 group per repeat unit (Bernfeld and Kelley, 1963). The potency of the inhi- 

 bition is independent of the configuration of the polysaccharide, whereas 

 in the case of the chicken enzyme the highly branched polymers are less 

 effective than the more linear ones. 



Polynucleotide Phosphorylase 



This enzyme, usually obtained from Azotobacter vinelandii or Micrococcus 



lysodeikticus , catalyzes the synthesis of polynucleotides, such as polyade- 



nylate: 



ADP + (A.AIP)„ ^ P, + (AMP)„^i 



The synthesis of a particular polynucleotide may be inhibited by another 

 polynucleotide; thus polyuridylate inhibits the synthesis of poly adenylate, 

 and polyuridylate, poly adenylate, and RNA inhibit the synthesis of poly- 

 cytidylate (Mii and Ochoa, 1957). The formation of polyadenylate has been 

 shown to be inhibited by variously degraded yeast RNA and polyadenylate 

 (Hendley and Beers, 1959, 1961; Beers, 1961). Increase in substrate con- 

 centration reduces the inhibition but not in a strictly competitive fashion. 

 Competition with primers or activators was considered to be the most likely 

 mechanism. If the polynucleotides are too extensively depolymerized, the 

 inhibitory activity falls, indicating a certain minimal chain length for op- 

 timal inhibition. It was also established that phosphate groups on or adja- 

 cent to the 3'-position of the terminal ribose units are necessary. It is im- 

 portant to remember in such systems that interactions between different 

 polynucleotide chains, perhaps through hydrogen bonding, can occur (Warn- 

 er, 1957); the possible role of such interactions in the inhibitions observed is 

 not yet completely understood. 



