Rat heart pyrophosphate phosphohydrolase activities. Sub-cellular distribution, catalytic properties, and hormonal responses

• 1.

  1. Inorganic pyrophosphate metabolism in cardiac tissue homogenates has been investigated.

• 2.

  2. A sub-cellular distribution study indicated that the predominant PP_i-metabolizing activity is Mg²⁺-stimulated soluble-fraction phosphohydrolase which is maximally active in the range pH 7–7.5.

• 3.

  3. Relatively small amounts of activity also were detected in particulate fractions at pH 7.3 in the presence of Mg²⁺. Activity was essentially absent from all fractions at pH 5.6 without added Mg²⁺.

• 4.

  4. PP_i-glucose phosphotransferase activity¹ could not be detected in any sub-cellular fraction or in homogenates.

• 5.

  5. Catalytically, the soluble fraction activity resembles a number of other PP_i phosphohydrolases with respect to (a) absolute requirement for Mg²⁺, (b) alkaline pH optimum (pH 7.3 for the heart enzyme), and (c) marked sensitivity to Ca²⁺ inhibition.

• 6.

  6. Alloxan diabetes produced an approx. 33% drop in PP_i phosphohydrolase activity. Insulin administration, adrenalectomy, or cortisone treatment did not produce statistically significant changes in levels of enzymic activity.

• 7.

  7. Inhibition due to Ca²⁺ was reversed by EDTA or additional Mg²⁺, but not by supplemental PP_i. Citrate inhibited the system both in the presence and absence of Ca²⁺.

• 8.

  8. A feedback mechanism for retardation of calcification in the vascular system of and near the heart is suggested based on the observations that (a) heart PP_i phosphohydrolase is extremely sensitive to Ca²⁺ inhibition, and (b) calcification of the aorta is inhibited by PP_i (ref. 2).