Studies on the roles of apotransferrin and caeruloplasmin (EC 1.16.3.1) on iron absorption in copper-deficient rats using an isolated vascularly- and luminally-perfused intestinal preparation.

1. Studies have been made on the effects of dietary copper on the iron and Cu distribution in rats and on the metabolic activity and absorptive capacity of intestines perfused both vascularly and luminally. 2. Rats maintained for 4-5 weeks on a Cu-deficient diet (0.4 microgram Cu/kg) had significantly lower plasma, liver and intestinal Cu concentrations and significantly reduced plasma caeruloplasmin and liver cytochrome c oxidase (EC 1.9.3.1) activity compared with controls receiving a Cu-supplemented diet (5 micrograms Cu/kg). Disturbances in Fe metabolism in Cu-deficient rats were evident as shown by a mild anaemia, significantly elevated hepatic Fe concentrations and hypoferraemia. 3. Intestinal glucose uptake from both the luminal perfusion medium (LPM) and vascular perfusion medium (VPM) was unaffected by Cu deficiency despite a significant (25-30%) reduction in oxygen consumption. This was associated with a 40% decline in mucosal cytochrome c oxidase activity. 4. In studies of Fe absorption, Fe uptake from the LPM was unaffected by Cu deficiency while transfer of Fe to VPM was significantly reduced (50%) compared with control preparations. Addition of apotransferrin (1 g/l) to the VPM was without effect in preparations from control rats but significantly increased the transfer of Fe to the VPM in preparations from Cu-deficient rats without affecting Fe uptake from the LPM. 5. The addition of either human or porcine caeruloplasmin (together with apotransferrin) to the VPM, such that the resultant ferroxidase (EC 1.16.3.1) activity of the VPM supernatant fraction was four to five times that of normal rat plasma, was without effect on either Fe uptake, tissue retention or Fe transfer to the VPM by preparations from either Cu-deficient or control rats. 6. These findings offer no evidence in support of the proposed role for caeruloplasmin with its associated ferroxidase activity in Fe absorption in the rat.

Glucose uptake and iron absorption by an isolated, vascularly and luminally perfused preparation of rat small intestine.

Some characteristics of an isolated vascularly and luminally perfused rat intestinal preparation are described. Over 60 to 90 min perfusion, the vascular perfusion medium (VPM) 'arterial' pressure remained stable and between animals it varied between 22 and 47 mmHg while the VPM flow rate remained constant at 1.3 ml/min. Hypersecretion, as monitored by changes in the concentration of phenol red in the luminal perfusion medium (LPM), did not generally occur. Histological examination of the tissue post-perfusion showed that normal morphology was retained for at least 1 h. Total glucose uptake ranged between 85 and 155 mumol/(g dry wt. h) with greater uptake from the VPM than the LPM. Approximately 50% of the glucose taken up by the intestine appeared as lactate in the perfusion media, most of which was released to the VPM. The addition of phloridzin (5 x 10(-4) M) to the LPM significantly reduced the uptake of glucose from the LPM and its transfer to the VPM. Iron absorption was studied by adding FeCl2 (with 59Fe and ascorbate, 100 micrograms/ml) to the LPM to give a final concentration of 10-100 micrograms iron/ml. The appearance of iron in the VPM was investigated over a period of 1 h. At the two lowest concentrations (10 and 25 micrograms/ml) there was a lag of 20-40 min before iron appeared in the VPM. At the higher doses (50 and 100 micrograms/ml) the lag was 10 min. During the final 20 min the appearance of iron in the VPM plateaued to dose-dependent constant rates. The ratio of the specific radioactivity of 59Fe in the two perfusates (LPM:VPM) was unity when the initial iron concentration was 25 micrograms/ml or above. At the lowest dose (10 micrograms/ml) this ratio was 2.5 indicating that during transfer, iron taken up from the LPM had mixed with a small labile endogenous iron pool. Both amounts of iron retained by the intestinal tissue and transferred to the VPM increased exponentially with increasing luminal iron dose. The amount of iron retained by the tissue was always greater than that transferred to the VPM.

Studies on the effects of dietary zinc dose on 65Zn absorption in vivo and on the effects of Zn status on 65Zn absorption and body loss in young rats.

Weanling male rats were maintained on diets containing 5, 10, 20, 40, 80 or 160 mg zinc/kg for 14 d. On day 15 they received 65Zn either by intraperitoneal injection or in a test meal containing 20 mg Zn/kg. After dosing, the rats were again maintained on the diets they had received previously. Whole-body 65Zn retention was measured immediately after dosing and daily for a further 9 d. From regression analysis of the semi-logarithmic plots of 65Zn retention from 0 to 192 h after 65Zn administration, the true extent of 65Zn absorption and the biological half-life (t1/2) of body 65Zn stores were calculated. At the end of the experiment, the rats were killed and the entire small intestines of some rats from each group were rapidly flushed out to remove food and faecal residues, frozen in liquid nitrogen and stored under an atmosphere of N2 at -20 degrees before separation of cytosolic Zn-binding fractions by gel filtration on Sephadex G-75. The results suggest that rats which received diets that were either deficient (5 mg Zn/kg), marginal (10 mg Zn/kg) or adequate (20-80 mg Zn/kg) in Zn achieved homeostatic regulation of body Zn by changes in both the extent of Zn absorption and excretion. However, when Zn supply was excessive, increasing from 80 to 160 mg Zn/kg, no further changes were seen in Zn absorption, and homeostatic control appeared to be effected entirely by changes in rates of body Zn loss. Gel chromatography of intestinal cytosol on Sephadex G-75 revealed that Zn was associated with two major fractions. The first (peak 1) had a molecular weight (MW) greater than 75 kdaltons and the second (peak 2), a MW of approximately 10 kdaltons and was assumed to be metallothionein. There was no obvious relation between the amount of Zn bound to peak 1 and dietary Zn content. In contrast, the amount of Zn recovered in peak 2 increased linearly with increasing dietary Zn content. Comparisons between the effect of dietary Zn content on Zn bound to peak 2 and 65Zn retention may, depending on the range of Zn intakes, indicate possible roles for intestinal metallothionein in the control of Zn absorption or excretion. A study of the effects of dietary dose of 65Zn on the extent of 65Zn absorption in rats of normal Zn status indicated a possible biphasic relation. At low doses (5-40 mg Zn/kg) 65Zn absorption appeared to exhibit a curvilinear response to increasing 65Zn dose, indicating possibly a saturable process.(ABSTRACT TRUNCATED AT 400 WORDS)

Hydatidiform mole coexisting with a live fetus: a dilemma of management. A recent review (1965-1985) and report of 2 new cases.

A review of 24 patients with a molar placenta and coexisting live fetus, including 2 new cases from the Queensland Trophoblastic Disease Registry, was made. The rate of fetal abnormalities was 33%; all 8 abnormal fetuses were female and in 5 of them in whom cultures were performed the chromosomal karyotype was triploidy 69XXX. There were 3 patients in whom malignant sequelae were detected (12%). After a confident ultrasound diagnosis of a molar placenta and a coexisting live fetus, the decision on whether the pregnancy should be terminated or allowed to continue should be based on the likelihood of the fetus being abnormal. It is recommended that the chromosomal karyotype and amniotic fluid alpha-fetoprotein level be determined by amniocentesis at about 16-18 weeks. This should allow those pregnancies in whom the fetus is potentially normal to be selected for conservative management.

Studies on the effect of copper deficiency on rat liver mitochondria. III. Effects on adenine nucleotide translocase.

Liver mitochondria from Cu-deficient rats exhibit impaired State 3 respiration (oxygen consumption in the presence of exogenous ADP) compared with Cu-adequate controls, whereas State 4 respiration (oxygen consumption after depletion of exogenous ADP) and ADP/O are unaffected. In view of previous observations (Davies, N.T., Lawrence, C.B., Mills, C.F. and Nicol, F. (1985) Biochim. Biophys. Acta 809, 351-361) it seemed that a decline in cytochrome c oxidase activity (EC 1.9.3.1) could not fully account for these findings. Cu deficiency resulted in a significant decline (40%, P less than 0.01) in [14C]ADP uptake by liver mitochondria which suggests there is a reduced activity of the adenine nucleotide translocase. The reduced translocase activity was not associated with any marked change in fatty-acid composition of either intact mitochondria or inner mitochondrial membranes. Inhibitor titrations with the irreversible inhibitor carboxyatractyloside showed that 'Cu-deficient' mitochondria required the same concentration of inhibitor to produce 100% inhibition of State 3 respiration as control mitochondria, suggesting that the amount of functional translocase enzyme present is unaffected. When the translocase assay was allowed to proceed until equilibrium was established between external and internal nucleotides, it was apparent that the exchangeable adenine nucleotide pool of Cu-deficient mitochondria was 36% lower than in controls. Analysis of mitochondria for their ATP, ADP and AMP contents showed that, whereas the AMP content was unaffected, ATP and ADP contents were 39 and 40% lower, respectively, which resulted in a significantly reduced pool of total adenine nucleotides (ATP + ADP + AMP) and a reduced 'energy charge' [(ATP + 0.5 ADP)/(ATP + ADP + AMP)]. These results are discussed in relation to current concepts of the regulation and control of mitochondrial respiration.

The phytic acid mineral, trace element, protein and moisture content of UK Asian immigrant foods.

A study has been made of the protein, phytate, calcium, magnesium phosphorus, zinc, copper, iron and manganese content of raw and cooked, whole and ground pulses, of chapatis and of three types of chapatis flour as purchased and consumed by Asian immigrants in the UK. The protein, mineral and trace element contents of raw products were similar to those published in a previous study. In general, partial (ground) or total removal of the seed coat of pulses (ground and washed) was without effect on composition. Soaking the pulses followed by cooking under pressure was without effect on the protein, mineral and trace element composition, although it resulted in variable losses of phytic acid. In all instances greater nutrient and phytate losses were observed when the seed coat was completely removed. With nutrient and phytate losses were observed when the seed coat was completely removed. With the exception of lentils, the phytate: Zn molar ratios of cooked pulses and chapatis was greater than 15 and the [Phytate] X [Ca]/[Zn] (mol/kg) ratios of the chapatis and four of the 13 cooked dishes were greater than 0.5. Both of these ratios may provide useful indices of the bioavailability of dietary Zn. The results are discussed in relation to the possible inadequacy of available dietary Zn in some sections of the UK, Asian community.

A novel, simple and rapid method for the isolation of mitochondria which exhibit respiratory control, from rat small intestinal mucosa.

A method is described for the isolation of functional mitochondria from rat intestinal mucosa. Its novel feature is the removal of mucus from the initial homogenate by treatment with DEAE-cellulose. The preparations exhibited acceptable ADP:O ratios, high State-3 respiration rates, and respiratory control ratios in excess of 3 when succinate, beta-hydroxybutyrate, glutamate/malate and glutamine were test substrates.

Studies on the effects of copper deficiency on rat liver mitochondria. II. Effects on oxidative phosphorylation.

Effects of dietary copper deficiency in rats on respiratory enzymes of isolated rat liver mitochondria have been studied. After 2 weeks of Cu-depletion, cytochrome c oxidase (EC 1.9.3.1) activity had declined by 42% and between 4 and 8 weeks exhibited between 20 and 25% of the activity of control mitochondria. Activities of NADH cytochrome c reductase (EC 1.6.99.3) and succinate cytochrome c reductase (EC 1.3.99.1), were unaffected initially but declined by 32 and 46%, respectively, after 8 weeks of Cu-depletion. After 4 weeks there was a significant (34%) decline in succinate supported state 3 respiration with only a modest (18%) decline in state 4 respiration. The ADP:O ratio was unaffected by Cu-depletion after 6 and 8 weeks of dietary Cu-restriction. State 3 respiration was significantly reduced after 6 weeks when glutamate/malate or beta-hydroxybutyrate were used as substrates, whereas state 4 respiration and ADP:O ratios were unaffected. The fall in state 3 respiration was of sufficient magnitude at 8 weeks to cause a significant decline in the respiratory control ratio with all substrates. Comparisons between the relative activities of cytochrome c oxidase and reductase activities in Cu-deficient preparations, the relatively specific effect of the deficiency on state 3 respiration with all substrates tested and the ability to increase significantly oxygen consumption in excess of maximal state 3 respiration by the uncoupler 2,4-dinitrophenol suggest that the defect in Cu-deficient mitochondria cannot be attributed solely to the decreased activity of cytochrome c oxidase.

Studies on the effects of copper deficiency on rat liver mitochondria. I. Changes in mitochondrial composition.

As part of an investigation of the lesions of copper (Cu) deficiency a study was undertaken of the copper, iron, cytochrome and fatty acid composition of liver mitochondria from Cu deficient and Cu-adequate control rats. Cu concentrations were significantly decreased in whole liver, liver mitochondria and in blood plasma. Total iron was significantly increased in whole liver but remained at the normal level in mitochondria. Cytochrome c oxidase (EC 1.9.3.1) and its component cytochromes a and a3 were significantly reduced in liver mitochondria from Cu-deficient rats, whereas there was no effect on the concentration of cytochromes b, c1 and c. Evidence from comparisons between cytochrome c oxidase activity and the amount of enzyme present, as assessed from the mitochondrial cytochrome a and a3 content, suggests that in addition to an absolute loss of enzyme, Cu-deficiency adversely affects the efficiency of the residual enzyme. Severe Cu deficiency had no effect on 'ageing' or 'swelling' properties of liver mitochondria, indicating no marked effects on fatty acid composition. Fatty acid analyses demonstrated a slight but significant increase in docosapentenoic acid (22:5) of Cu-deficient mitochondria, but since this represents a minor component there was no change observed in the 'unsaturation index'. It was concluded that, in contrast to previous reports, Cu deficiency of the severity reported did not have a deleterious effect on the integrity and permeability of the inner mitochondrial membrane as exemplified by any qualitative modification of fatty acid constitution per se.

Some nutritional aspects of trace metals.

A brief outline of the known biochemical roles of manganese and chromium is given before the problems of determining human trace metal status are discussed. The factors predisposing to trace metal deficiency are reviewed but particular emphasis is placed upon those which alter the bioavailability of essential trace metals from natural and synthetic diets. This is illustrated by practical examples which show the importance of investigating the bioavailability of the trace metal content of artificial diets used in paediatric care. The results of such studies highlight the need to assess similarly the adequacy of the trace element composition of the many meat substitutes and extenders available currently. Finally, some aspects of trace metal supplementation of intravenous feeding regimens are described.

Pancreatic atrophy in copper-deficient rats: histochemical and ultrastructural evidence of a selective effect on acinar cells.

Copper deficiency had a differential effect between tissues in the rat pancreas. There was marked loss and atrophy of acinar cells, in which both hypertrophied and degenerating mitochondria were present. Cytochrome oxidase activity in acini was greatly depleted while monoamine oxidase activity was enhanced. Atrophy of acinar cells was accompanied by extensive degeneration of the rough endoplasmic reticulum, and by a failure of zymogen granule synthesis. These changes contrasted strongly with the appearance of non-acinar tissues, in which hypertrophy and degeneration of mitochondria were rarely observed. Islet tissue, pancreatic ducts and blood vessels showed no atrophic changes. Cytochrome oxidase activity in islet tissue, and in the epithelium of the main pancreatic ducts, appeared unaffected.

Noradrenaline concentrations in gut muscle and mucosa of the copper-deficient steer and rat.

1. Noradrenaline (NA) concentrations in the duodenum and colon of copper-deficient and Cu-adequate steers and rats were determined. 2. In Cu-deficient steers exhibiting diarrhoea, there were significant decreases (P less than 0.05) in duodenal and colonic muscle NA concentrations. Duodenal and colonic mucosal NA concentrations in the steer were also diminished by Cu deficiency but this effect was not statistically significant. 3. Rat intestinal musculature had a higher NA concentration than that of the steer. Rat duodenal muscle NA was not influenced by Cu deficiency, but increased markedly with age. 4. It is suggested that the decline in NA concentration of cattle musculature in copper deficiency may have a role to play in the aetiology of diarrhoea in such animals.

An appraisal of the newer trace elements.

For an element to be considered essential it should satisfy three criteria: (1) it must be present in living matter; (2) it must be able to interact with living systems; (3) a dietary deficiency must consistently result in a reduction of a biological function, preventable or reversible by physiological amounts of the element. Ideally, essentiality should be established in more than one species and confirmed in more than one laboratory. Since 1970, vanadium, fluorine, silicon, nickel and arsenic have been shown to meet all the criteria listed above, and evidence from one laboratory has indicated that tin may have an essential biological role in the laboratory rat. A review is presented of the evidence on which the essentiality of these elements has been established and, when known, an indication of their biochemical functions. The possible significance of these 'newer' trace elements to the health of man and animals is discussed.

Studies on the absorption of zinc by rat intestine.

1. A technique is described for the measurement of the extent of 65Zn absorption by different regions of the intestine in the intact rat. Using this technique it was shown that the duodenum contributed 60%, the ileum 30% and the jejunum 10% to the over-all absorption of 65Zn. Negligible absorption of 65Zn occurred from the caecum and colon. 2. Using ligated loops of rat duodenum in situ, 65Zn absorption was shown to be rapid, with 1% of a 5 microgram dose being transferred to the carcase within 1 min of intraluminal dosing. 3. When 65Zn was injected into ligated loops in a dose range of 1--200 microgram Zn/ml the rate of absorption was linear with respect to time over the first 15 min. The rates of 65Zn absorption v. dose of 65Zn exhibited saturation kinetics indicating absorption by a 'carrier' or enzyme-mediated process. 4. The binding of 65Zn to loop tissue showed biphasic kinetics which suggested that at low intraluminal concentrations of Zn (1--50 microgram Zn/ml) binding was to specific sites whereas, at higher concentrations (50--200 microgram Zn/ml), non-specific binding occurred. 5. A study of the fate of mucosally bound 65Zn showed that over the first 30 min a proportion of the 65Zn was rapidly transferred to the carcase and this was probably associated with the rapid phase of 65Zn absorption described previously. From 30 min up to 6 h after the initial binding, 65Zn was also transferred to the carcase albeit at a much slower rate indicating a slow phase of Zn absorption. A study of the kinetics of this slow phase indicated that the loss of bound 65Zn to the body was a saturable process indicating an enzyme- or 'carrier'-mediated process. A comparison of the kinetics of the slow and rapid phases of 65Zn absorption suggests that these processes are distinct. 6. Histological examination of mucosal tissue of loops exposed to 200 microgram Zn/ml revealed to discernable diamage. Similarly, no effect was observed on either arginine or glucose uptake by isolated duodenal loops in situ, although this concentration of Zn completely abolished fluid uptake. A study of the effect of different doses of Zn showed that 50 microgram Zn/ml inhibited mucosal fluid uptake by more than 50% and 100 microgram Zn/ml by more than 90%. It was concluded that these effects were due to a specific action on the fluid-transfer process and not due to a general poisoning of the mucosa.

An evaluation of the phytate, zinc, copper, iron and manganese contents of, and zn availability from, soya-based textured-vegetable-protein meat-substitutes or meat-extenders.

1. A study has been made of the zinc, copper, iron, manganese, protein (nitrogen X 6.25) and phytic acid contents of nineteen soya-bean-based textured-vegetable-protein (TVP) meat-extenders and meat-substitutes and of three "ready-prepared" canned meals containing TVP. 2. Phytate analysis was performed using a newly-developed method based on Holt's (1955) procedure. This method enabled the phytate content of milligram quantities of TVP to be estimated, with an SD for six replicates of 3%. 3. The Fe, Cu and Mn contents (mg/kg) of the meat extenders or meat-substitutes varied, with values of 59.4-144, 14.1-19.7 and 19.5-29.1 respectively. The protein content of these products was approximately 500 g/kg. 4. The phytate content of the meat-extenders and meat-substitutes ranged from 11.0 to 20.2 g/kg and the Zn content from 35.0 to 49.4 mg Zn/kg. The calculated molar ratio, phytate: Zn varied from 25 to 42. 5. The trace element, phytate and protein contents of the "ready-prepared" canned meals were 30-50% lower than the meat-extenders and meat-substitutes. 6. Cooking the "ready-prepared" meals as specified by the manufacturers was without effect on the trace element or phytate content. 7. When TVP was fed to rats as the only protein source, they had significantly lower growth rates and plasma Zn concentrations than rats given an egg-albumen-based diet of similar Zn content (14.5 mg Zn/kg). Supplementation of the TVP diet with Zn (100 mg Zn/kg) significantly increased growth rate and plasma Zn concentration whereas Zn supplementation of the albumen diet was without effect. 8. The possible implications of consumption of TVP products in relation to Zn status of the human population is discussed.

Studies on the phytate: zinc molar contents in diets as a determinant of Zn availability to young rats.

1. Studies were carried out in vitro to examine the effects of phytate on the solubility of the trace elements zinc, copper and manganese. Appropriate volumes of a solution of sodium phytate were added to a mineral solution to achieve phytate: Zn values of from 0 : 1 to 45 : 1. In a second series the same values for phytate: Zn were achieved by varying the amount of added Zn at a fixed phytate concentration. 2. In both experiments greater than 85% of the Zn was rendered insoluble at pH 6.5 even at the lowest value for phytate: Zn (5 : 1). The effect of phytate on Zn solubility was greater than effects on Cu or Mn. 3. In a dietary study, rats were offered a semi-synthetic egg-albumin-based diet with added phytate. Two series of diets were prepared, the first had a constant Zn content (18.5 mg Zn/kg) and the amount of sodium phytate varied so as to achieve values for phytate: Zn of from 0 : 1 to 40 : 1 (series 1). In the second series, the same values for phytate: Zn were achieved by adding a fixed amount of phytate (7.4 g phytic acid/kg) while the amount of Zn was varied (series 2). 4. Dietary phytate caused significant reductions in growth rates, plasma Zn concentrations and hair Zn concentrations and greying of the coat at values for phytate: Zn of 15 : 1, 10 : 1, 15 : 1 and 15 : 1, respectively. 5. While phytate was apparently slightly more effective in reducing Zn status when phytate: Zn values were achieved at the lower absolute levels of phytate and zn (series 1 diets), the differences at equivalent phytate: Zn values were small. It was concluded that phytate: Zn values can be used as an indicator of Zn availability from phytate-rich diets. 6. Rats offered three diets containing soya-bean-based textured-vegetable-protein (TVP) exhibited low rates of weight gain compared with rats offered an egg-albumen-based diet of similar Zn content (14.5 mg Zn/kg). Additional Zn supplied in drinking-water (25 mg Zn//l) was without effect on rats consuming the egg-albumin diet but significantly improved the weight gain of rats on the TVP diets. 7. It was concluded that phytate naturally present in TVP behaves similarly to phytate added to an otherwise phytate-free diet and that the reduced availability of Zn in TVP diets can be accounted for entirely by their phytate contents.

Perinatal changes in the absorption of trace elements.

Fetal demands for many of the essential trace elements change markedly during the terminal stages of development. Susceptibility to deficiency during early postnatal life is influenced by the extent of fetal trace element reserves, by inadequacies in the supply of some elements in maternal milk and by postnatal changes in the efficiency of trace element absorption. The efficiency with which essential and some toxic trace elements are absorbed after birth is a function both of age and of diet. Homeostatic mechanisms for the control of iron absorption are poorly developed in the newborn. There are indications that pinocytotic absorption of iron, copper, lead and cadmium may occur at this stage and account for the high efficiency with which these elements are absorbed from a liquid diet. Evidence of developmental changes in the enterohepatic recirculation of such metals is considered and an account is given of our very inadequate understanding of the processes of trace metal absorption in the weaned animal.

Metabolism of 35S-labelled copper-, zinc-and cadmium-thionein in the rat.

A comparative study has been made of the metabolism in the rat of intravenously-administered hepatic copper-, zinc- and cadmium-thioneins. In all cases the 35S-labelled protein was rapidly removed from the circulation. About 20% of the 35S was present in the kidneys after 30 min byt only small amounts of 35S were found in the liver, intestinal mucosa or pancreas. In the case of copper-thionein, 30% of the injected 35S was recovered in the urine within 2 h, mainly as intact copper-thionein. The 35S which appeared in the kidneys was also present initially as metallothionein but this was degraded very rapidly, especially when zinc-thionein was give. Both copper and cadmium from the injected proteins accumulated in the kidneys as metallothionein, but there was no increase in renal zinc concentrations in the rats dosed with zinc-thionein. These findings are discussed in relation to the development of renal damage in chronic cadmium and copper toxicity.

Effect of zinc status of rats on the synthesis and degradation of copper-induced metallothioneins.

Injection of Zn2+-adequate and Zn2+-deficient rats with Cu2+ stimulated the incorporation of l-[35S]cysteine into a low-molecular-weight Cu2+-binding protein in both liver and kidney. No significant incorporation of l-[4,5-3H]leucine into this protein occurred, confirming the previous claim that it was metallothionein and not some other leucine-rich protein. The half-life of the protein was found to be 16.9 +/- 1.0 (S.E.)h in the liver of Zn2+-adequate rats but only 12.3 +/- 0.5h in Zn2+-deficient animals. The degradation rate of the metallothionein was similar to the rate of disappearance of Cu2+ and Zn2+ from the protein, indicating that the release of mental from the protein and its catabolism occurred simultaneously. There was no significant difference in the half-lives of the hepatic or renal copper-thioneins in Zn2+-adequate rats.