Owen, Charles A.

SummaryWhen 125I-labeled canine prothrombin was given to normal adult dogs intravenously, it was calculated that 240% of the plasma prothrombin crossed the capillary barrier per day, 410% of the interstitial prothrombin returned to the blood stream daily, and 79% of the plasmatic prothrombin was catabolized per day. These data are in close agreement with those observed for bovine prothrombin in calves by Takeda (1970).When derived from normal dog prothrombin, prethrombin-1 is a mixture of 2 polypeptides, one larger than the other, and both present in about equal amounts. The longer peptide, “prethrombin-1-long,” was catabolized twice as fast as prothrombin, and the shorter, “prethrombin-1-short,” 4 times faster. Prothrombin fragment-1 was catabolized by the normal dog still more rapidly.The catabolism of prothrombin was not accelerated in 3 dogs receiving continuous infusions of a thromboplastic emulsion of dog brain. Nor was the level of prothrombin in their plasma remarkably altered.

Copper-laden Bedlington terriers were found to absorb copper normally, based on the ratio of 64Cu in bile and in plasma ceruloplasmin after oral and intravenous doses of the radionuclide. The excessive accumulation of the copper in Bedlington terriers was due to impaired biliary excretion of the metal, The abnormal Bedlington pattern was simulated in normal dogs by biliary obstruction. Although the Bedlington terriers excreted more copper in their urine than normal, the amount was far less than that accumulated secondary to inadequate biliary excretion. These abnormalities are shared by patients with Wilson's disease, both conditions being inherited on an autosomal recessive basis. copper absorption; copper excretion; radiocopper; Wilson's disease Submitted on May 5, 1981 Accepted on March 30, 1982

About 100 µg of copper as cupric acetate-Cu64 was given iv to adult, male rats. Maximal concentrations of Cu64 were reached quickly in the excretory organs—liver, kidney, and gastrointestinal tract—which then slowly released their radioactivity. In most of the other organs a progressive accumulation of Cu64 began after the disappearance of most of the nonceruloplasminic Cu64 from the plasma and after ceruloplasmin-Cu64 emerged in the plasma, suggesting that ceruloplasmin may be the copper donor for the tissues. The disappearance of plasmatic Cu64 tended to parallel that from the liver after the first 48 hr.

The concentrations of copper in organs of white male rats were measured. Highest concentrations were in the kidney (5.1 µg/g wet wt.), liver (4.4), heart (4.5), and pituitary (about 5). Hair contained about 30 µg/g. From the weights of the organs and their copper concentrations, the total copper contents of the organs and of the whole rat were calculated. The whole rat (250 g) contained slightly less than 0.5 mg, of which about half was in the skin and muscle. Balance studies indicated that approximately 300 µg of copper was excreted daily, almost exclusively in the feces. Relatively small amounts of copper were excreted in urine. When expressed as proportion of body weight, the weights of testes, pancreas, skin, and eyes were larger in the rat than in man, and adrenals, brain, and thyroid were considerably smaller.

Varying doses of Cu64-labeled cupric acetate were given orally or intravenously to adult male rats. The urinary and fecal excretion of Cu64 was measured in intact rats and in rats with obstruction of the common duct. In addition, the biliary Cu64 was assayed in rats with biliary fistula. Only about half to two-thirds of doses up to 1 µg of copper were absorbed; the site of absorption seemed to be the upper portion of the small intestine. With larger doses, the percentage absorbed fell, but the absolute amount increased. Much less copper was excreted in the feces when the rat had a biliary fistula, the difference being accounted for by the biliary Cu64. Fecal excretion was not prevented by duodenostomy below the pancreatic and biliary ducts and therefore presumably reflects excretion through the gut mucosa. Significantly more copper was excreted in the bile and in the urine when the Cu64 was given intravenously. Very little of the biliary Cu64 was absorbed from the gut of intact rats when it was given by stomach tube.

The isolated, perfused rat liver has been used to study the metabolic pathways of I131-labeled l-thyroxine (T4), l-3,5,3'-triiodothyronine (T3), their partially deiodinated derivatives, and d-thyroxine. l-Thyroxine was metabolized less rapidly than the l-thyronines with fewer iodine atoms. l-T4 accumulated in the liver more rapidly than l-3,3',5'T3 or l-3,3'T2 but less rapidly than l-3,5,3'T3 or d-T4. Conjugation with glucuronic acid proceeded in the liver most rapidly from 3,5,3'T3 and at much lower rates from d-T4, l-T4, l-3,3',5'T3, and l-3,3'-diiodothyronine (T2). Deiodination of l-3,3',5'T3 and l-3,3'T2 proceeded most rapidly.