Copper Metabolism in Cattle

• first shown to be essential for growth/development/haemoglobin production in lab rats in 1920s • grazing ruminants with chronic wasting diseases found to respond to copper therapy (e.g Sawyback - ataxic disease of newborn lambs, neuromuscular condition unable to stand) • copper deficient soils affecting livestock and vegetation

Yes required in small quantities (mg/kg DM) cattle need 15-30mg/kgDM of copper

a chemical compound required by an enzyme as a catalyst

enzyme that requires copper for respiration in the electron transport chain as an electron acceptor responsible to generate energy for all tissues antioxidant - prevent tissue damage from free radicles and get rid of waste produced during respiration

Hepheastin - transport of iron from intestines, influx of iron across basolateral membrane into cells of intestinal tract

• copper dependant enzyme required for generation of appetite regulating hormones gastrin and CCK serum/tissue of • activity in PAM rats positively correlated with dietary intake of copper

• occurs in duodenum • enters enterocytes ACTIVE transport from lumen • exits by active transport into blood • Cu2+ to Cu by brush boarder metalloenzymes at apical surface then transported across apical membrane of enterocyte by CTR1 (high affinity copper transporter • Cu transported into golgi network = synthesis of metalloenzymes (e.g hepheastin) OR shuttled by atox1 to ATP7A into bloodstream

to the liver(copper homeostasis main organ) Cu bound to serum albumin with transcuprien and histidine

storage organ regulates copper excretion in bile secrete copper into blood for transport to tissues

• liver • Cu uptake into hepatocytes mediated by CTR1 • Cu binds to cytosolic copper chaperones for intracellular transport • after transfer across gut = enter portal vein • free intracellular copper stored in vesicular copper pools • liver fluke infestations can limit how much Cu liver can store

• storage (mainly in MT) • excretion (transpored into bile) • transit (enters enzymes)

ATP7B translocates to the cell membrane and pumps copper out of cell

Ceruloplasmin (CP)= main transport protein - binds 6 Cu ions consists of 90% plasma Cu CP produced at steady rate however studies in mice found after gene deletion for CP still metabolise copper

• change coat colour (black to white wool), swayback in lambs • infertility (anoestrus, lack of oestrus behaviour), Reduced growth rate poor FCR (feed conversion efficiencies) • uneven bone growth = osteochondrosis • connective tissue dysfunction (e.g. lesions in ligamentum nuchse supporting neck lead to dislocation causing head to drop and create a ‘hump’ • heart func, immune func, • RBC formation (haemoglobin synthesis declines)

• primary - lack of Cu in diet (unlikly problem in UK, tolerate low Cu) • Secondary - antagonists affecting Cu metabolism (e.g. molybdenum, sulphur, iron, zinc) lead to copper responsive disorders Suttle (1990) concluded Mo+S interactions main cause of Cu deficiency

may look clinically well and give it copper supplementation and its health may improve if clinically or sub clinically deficient, respond to copper treatment

Thiomolybdates (MoS4) prevents absorption of copper can cause copper deficiency - sulphide formed by ruminal microorg from dietary sulphate/organic sulphate compounds molybdenum only exerts limiting effect on copper retention in presence of sulphur

• Mo and S form monothiomolybdates (TM1) - breakdown acidity of abomasum • become TM3 • become TM4 (tetra-thiomolybdates) collect copper, dont allow absorption • further along sequence = more stable • more Mo and S in diet = further along sequence TM formed

• excreted in faeces • absorbed into blood and excreted through bile or stored in liver. exert systematic effect on Cu metabolism in excess • go into tissues - thiomolybdate removes Cu, inactivates enzymes = toxic

mass release of Cu into the bloodstream, excess copper induce production of superoxide radicals which cause RBC membrane damage mass hepatic degeneration, liver breaks down, metabolic shut down

• jaundice (excessive breakdown of rbc leading to bile accumulation) • dark urine • blood dullness • death

higher copper absorption in young decreased copper absorption in adults can still look clinically heathy with build up of copper

10-15 mg Cu/kg DM

• pasture/food/crops depending on soil Cu, drainage, herbage species • normal pasture range = 4-8mg/kg DM • low in milk