Intracellular Distribution of Hepatic Cooper in Normal and Copper-Loaded Sheep

Corbett, W. S.; Saylor, W. W.; Tan, Lei; Leach, R. M.

doi:10.2527/jas1978.4751174x

Cited by 13 publications

(10 citation statements)

References 12 publications

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“…However, earlier studies by our research group [ 56 ] indicate that cattle have a poor capacity to induce metallothionein and accumulate metallothionein-bound copper. In addition, copper distribution in the different subcellular fractions in cattle [ 57 , 58 ] is very similar to that described in sheep, in which the proportion of copper is generally highest in the large-granule fraction, followed by the cytosol and the nucleus, with only a small proportion in the microsomal fraction [ 44 , 45 , 46 , 49 ]. In many other mammalian species, most copper in the liver (i.e., 50% or more) occurs in the cytosol, and only a small proportion (20%) occurs in the large-granule fraction [ 44 , 45 ].…”

Section: Hepatic Copper Accumulation In Ruminantssupporting

confidence: 55%

“…In addition, copper distribution in the different subcellular fractions in cattle [ 57 , 58 ] is very similar to that described in sheep, in which the proportion of copper is generally highest in the large-granule fraction, followed by the cytosol and the nucleus, with only a small proportion in the microsomal fraction [ 44 , 45 , 46 , 49 ]. In many other mammalian species, most copper in the liver (i.e., 50% or more) occurs in the cytosol, and only a small proportion (20%) occurs in the large-granule fraction [ 44 , 45 ]. Differences in the intracellular distribution of copper in sheep, cattle and other species that are less susceptible to copper toxicity may be explained by the limited metallothionein-synthesizing capacity of ruminants [ 44 ].…”

Section: Hepatic Copper Accumulation In Ruminantssupporting

confidence: 55%

“…Because of the susceptibility of sheep to chronic copper toxicity and the clinical similarity to copper disorders in humans, hepatic copper metabolism has been widely studied in sheep [ 43 , 45 , 46 , 47 , 48 , 49 ] and susceptibility is considered to be related to the inability of sheep to accumulate large amounts of copper as metallothionein in the liver. While the role of metallothionein in copper metabolism has not been completely elucidated, it is generally considered to act as a storage buffer protecting the cell against free copper [ 24 ].…”

Section: Hepatic Copper Accumulation In Ruminantsmentioning

confidence: 99%

“…While the role of metallothionein in copper metabolism has not been completely elucidated, it is generally considered to act as a storage buffer protecting the cell against free copper [ 24 ]. Studies of hepatic subcellular distribution in sheep [ 44 , 45 , 46 , 49 ] have shown that, as in most mammals, copper mainly accumulates in the cytosol bound to metallothionein during the early stages of copper accumulation; however, unlike other species, sheep have a limited capacity to accumulate large amounts of Cu-metallothionein in the liver, and saturation occurs very quickly. If there is a large influx of copper into the liver, the capacity of the metallothionein to bind copper and of the lysosomes to remove copper from the cytosol can be exceeded, and copper starts to accumulate at a higher rate in other organelles (mainly in the nucleus), while if accumulation is greater, copper may even remain as free copper ions in the cytosol; in both cases copper is responsible for major changes in liver structure and function [ 41 , 50 , 51 ].…”

Section: Hepatic Copper Accumulation In Ruminantsmentioning

confidence: 99%

“…The greatest difference is observed in the large-granule fraction, in which there is a gradual decrease in the rate of increase in copper concentration per unit increase in total liver copper concentration; the amount plateaus at around 450 mg/kg, i.e., at 4.5 times the generally accepted safe-adequate total liver concentration of copper in cattle [ 57 ]. Subcellular studies have shown that in sheep the large-granule fraction begins to plateau at hepatic copper levels of between 160 and 180 mg/kg wet weight, i.e., less than two times the safe-adequate concentration [ 44 , 45 , 46 ]. Other species such as rats are not as susceptible to copper toxicity, and the large-granule fraction becomes saturated at hepatic copper concentrations between 210 and 300 mg/kg wet weight, i.e., at almost 100 times the normal hepatic concentration [ 45 , 59 ].…”

Section: Hepatic Copper Accumulation In Ruminantsmentioning

confidence: 99%

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Copper Supplementation, A Challenge in Cattle

López‐Alonso

Miranda

2020

Animals

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Ensuring adequate copper supplementation in ruminants is a challenging task due to the complexity of copper metabolism in these animals. The three-way interaction between copper, molybdenum and sulphur (Cu-Mo-S) in the rumen makes ruminants, particularly cattle, very susceptible to suffering from secondary copper deficiency. Paradoxically, excessive copper storage in the liver to prevent deficiency becomes a hazard when ruminants are fed copper-supplemented diets even slightly above requirements. While cattle were traditionally thought to be relatively tolerant of copper accumulation, and reports of copper poisoning were until recently somewhat rare, in recent years an increased number of episodes/outbreaks of copper toxicity in cattle, particularly in dairy cattle, have been reported worldwide. The growing number of lethal cases reported seems to indicate that copper intoxication is spreading silently in dairy herds, urging the development of strategies to monitor herd copper status and improve farmers’ awareness of copper toxicity. In fact, monitoring studies carried out on numerous samples collected from culled animals in slaughterhouses and/or diagnostic laboratories have demonstrated that large numbers of animals have hepatic copper concentrations well above adequate levels in many different countries. These trends are undoubtedly due to copper supplementation aimed at preventing copper deficiency, as dietary copper intake from pasture alone is unlikely to cause such high levels of accumulation in liver tissue. The reasons behind the copper overfeeding in cattle are related both to a poor understanding of copper metabolism and the theory of “if adding a little produces a response, then adding a lot will produce a better response”. Contrary to most trace elements, copper in ruminants has narrow margins of safety, which must also be formulated considering the concentrations of copper antagonists in the diet. This review paper aims to provide nutritionists/veterinary practitioners with the key points about copper metabolism in cattle to guarantee an adequate copper supply while preventing excessive hepatic copper loading, which requires à la carte copper supplementation for each herd.

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Section: Hepatic Copper Accumulation In Ruminantssupporting

confidence: 55%

Section: Hepatic Copper Accumulation In Ruminantssupporting

confidence: 55%

Section: Hepatic Copper Accumulation In Ruminantsmentioning

confidence: 99%

Section: Hepatic Copper Accumulation In Ruminantsmentioning

confidence: 99%

Section: Hepatic Copper Accumulation In Ruminantsmentioning

confidence: 99%

See 3 more Smart Citations

Copper Supplementation, A Challenge in Cattle

López‐Alonso

Miranda

2020

Animals

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Absorption, Transport and Distribution of Copper

Bremner¹

1980

Novartis Foundation Symposia

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Influence of zinc on copper binding in tissue proteins of steers

Whanger

Deagen

1991

Biol Trace Elem Res

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Two experiments were conducted with steers fed diets containing 270 ppm copper either with or without 2050 ppm zinc. Liver biopsies were taken from steers biweekly for 10 wk for analysis. The steers were then killed; tissues were removed, homogenized, and centrifuged, and the pellets were extracted with mercaptoethanol (BME), and selected cytosols and extracts were subjected to gel filtration (Sephadex G-75). Copper and zinc were determined on the BME extracts, pellets after extraction, cytosols, and gel-filtration fractions. Copper accumulated at about the same rate in BME extract and in the extracted pellet, with the smallest amount in the cytosol. In contrast, over 70% of the zinc was present in the hepatic cytosols. Gel filtration of BME extracts revealed the greatest amount of copper in a low-mol-wt (MW) peak in addition to three minor peaks of copper. Within the hepatic cytosols, the greatest amount of copper accumulated in proteins of MW greater than 75,000, the next greatest amount in 30,000-MW proteins, and the least amount with metallothionein (MT) of steers fed the diet with only copper added. In contrast, the greatest amount of copper was present with MT in hepatic cytosols of the steer fed a diet that included copper plus zinc. Hence the zinc status of steers influences the deposition of copper in the cytosolic proteins (as demonstrated by liver, kidney, and pancreas), but not in the intracellular fractions.

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Intracellular Distribution of Hepatic Cooper in Normal and Copper-Loaded Sheep

Cited by 13 publications

References 12 publications

Copper Supplementation, A Challenge in Cattle

Copper Supplementation, A Challenge in Cattle

Absorption, Transport and Distribution of Copper

Influence of zinc on copper binding in tissue proteins of steers

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