COPPER

INTRODUCTION - Transition metal with 3 oxidation states: Cu0, Cu1+, Cu2+. Most often found in biologi s!stems as Cu 2+ - " need for Cu in higher animals has been suggested be ause hemo !anin, the ox!gen- arr!ing mole ule of in#ertebrates, was found to ontain Cu. - $n human, Cu %otensial essentialit! was re ogni&ed in 1'2(: )art et al found that Cu to be essential for er!thro%oiesis in rats fed a mil*-based diet. - The essentialit! Cu for humans was first shown during the 1'+0s in malnourished hildren from ,eru.

- These hildren had an anemia refra tor! to iron thera%!, neutro%enia - bone abnormalities that were res%onsi#e to Cu su%%l. DIETARY SOURCES - Con entration of Cu in food are highl! #ariable - .rgan meats, o!sters - ho olate ri hest sour es. )uman - ow mil* %oor sour es/ howe#er, 0M1CM - Cu on entration in 0M de lines with the time of la tation: olustrum ha#e the highest #alues. - Most infant formulas are su%%l. with Cu. The Cu ontent #aries de%ending on the need of the infant 2full3%reterm4

DEFICIENCY OF COPPER IN HUMAN 1. 5e reased Cu stores at birth %remature infant 607 are mu h more %rone to de#elo% Cu defi ien ! be ause of their redu ed storage of li#er Cu 2. $nade8uate Cu su%%l! - 6ow dietar! Cu $nfant fed ow mil* ex lusi#el! be ause of the minor ontent - low absor%tion CM om%ared 0M - 9hort breast-feeding time - 6ow bioa#ailabilit! of dietar! Cu - Total %arenteral or enteral nutrition with inade8uate Cu su%%l.

3. $n reased re8uirement )igh rate of growth during the rehabilitation %eriod :. $nade8uate Cu absor%tion - )igh oral inta*es of ;n, <e or =it C - Malabsor%tion s!ndrome 2 elia disease, !sti fibrosis, tro%i al - nontro%i al s%rue4 - 9ub>e t who re ei#ed %eni illamine - high doses of oral al*ali thera%! ?. $n reased losses - @e%eated or %rolonged e%isodes of diarrhea - "bnormal bile loss +. Aeneti Cu defi ien ! Men*es s!ndrome is an Blin*ed re essi#e disorder.

DIETARY FACTORS AFFECTING CU BIOAVAILABILITY $ron - Cu absor%tion ma! be affe ted b! high le#el of dietar! iron. @edu tion in li#er Cu on entrations when dietar! iron was in reased 10 fold - $n iron defi ien !, enhan ed iron absor%tion ma! interfere with Cu absor%tion - )igh dietar! iron affe ts Cu absor%tion onl! when Cu status is low or marginal. ,h!tate - fiber - 9e#eral studies in animal ha#e shown negati#e effe t - in human do not de rease Cu absor%tion

;n - ex essi#e ;n the Cu status of animals - humans is im%aired/ the effe t is re#ersed b! Cu su%%l. - )igh dietar! ;n indu es intestinal MT. Cu doesnCt %la! an im%ortant role in the indu tion MT but it has a stronger affinit! for MT than ;n. $t dis%la es ;n in intestinal MT - is tra%%ed. Carboh!drates $n rats, dietar! fru tose a%%ears to worsen the effe ts of Cu defi ien ! in that fe al urinar! ex retion Cu are ele#ated. "s orbid a id has negati#e effe t on Cu absor%tion. This effe t is a hie#ed b! redu tion of Cu2+ ions to Cu+ - that the latter form is less well absorbed.

FUNCTIONS 1. 0io hemi al as a %art of a number of %rotein, in luding man! im%ortant en&!mes. 1.1. Cu- ontaining en&!mes found in humans - "mine oxidases - Monoamine oxidase 2ina ti#ation ate holamine4, diamine oxidase 2ina ti#ates histamine4 - 6!s!l oxidase formation of onne ti#e tissue, in luding bone, blood #essels, s*in, lungs - teeth - <erroxidases erulo%lasmin - C!to hrome .xidase in mito hondria, ele tron trans%ort hain.

- 5o%amine -h!drox!lase on#ersion do%amine to the neurotransmitter nore%ine%hrine in the brain - 9.5 as a s a#enger of su%eroxide radi als %rote ts against oxidati#e damage - T!rosinase on#ersion of t!rosine to do%amine - the oxidation of do%amine to do%a8uinone, ste%s in the s!nthesis of melanin. 1.2. Cu-binding %rotein - Metallothionein Da h mole ule an bind 11 or 12 Cu atoms as well as ;n - Cd. The! a%%ear to %la! a role in metal storage - se8uester ex ess metal ions, %re#enting toxi it!.

- "lbumin binds - trans%orts Cu - Trans u%rein binds - trans%orts Cu 2. ,h!siologi - Conne ti#e tissue formation Cu is essential for ross-lin*ing of ollagen - elastin 2bone formation s*eletal minerali&ation4 - $ron metabolism erulo%lasmin - Central ner#ous s!stem re8uired for formation or maintenan e of m!elin, a %rote ti#e la!er o#ering neurons, ate holamine metabolism 2im%lies a fun tion in normal neurotransmission4. - Melanin %igment formation - Cardia fun tion

METABOLISM "bsor%tion - %rimaril! in the small intestine, with small amount in the stoma h - " ti#e trans%ort me hanism at lower le#els of dietar! Cu/ at high le#el of dietar! Cu, %assi#e diffusion %la!s a role. - "bsor%tion de lined from E?F at 0,: mg Cu3d to 12F at E,? mg Cu3d. 9torage: - "nimal data suggest that Cu is stored in the li#er, bound to MT-li*e %roteins - Cu ma! also be held, at least tem%oraril!, bound to intestinal MT

Trans%ort - Cu is trans%orted bound %rimaril! to albumin, transu%rein - low-mole ular-weight ligands - "lbumin was a ma>or binder of ioni Cu in the %lasma - .nl! 1(0 g Cu asso iated with albumin in human %lasma. The rest of the 1000 g Cu 2%er liter %lasma4 is bound to erulo%lasmin 2+?F4, trans u%rein 212F4 - om%onents of low mole ular weight - Cerulo%lasmin is not %art of ex hangeable %lasma Cu %ool - Ce% doesnCt dire tl! bind or in or%orate the

metal when ex%osed to Cu ion. Cu is added during the s!nthesis of Ce% b! the li#er - The affinit! of trans u%rein for Cu2+ must be higher than that of albumin be ause trans u%rein an hold almost as mu h Cu while %resent in mu h lower on entrations Dx retion - The %rimar! route of Cu ex retion is #ia bile into the A$ tra t. 6ittle of this Cu is reabsorbed. - .ther routes of ex retion ontribute little to total Cu losses. .nl! 10 G 30 g of Cu in the urine.

ASSESSMENT OF COPPER STATUS 1. Serum / pla ma Cu !"#!e#$ra$%"# - @outinel! measured for lini al assessment of se#ere Cu defi ien !, but not sensiti#e - s%e ifi enough to be used as an index of Cu status in health! indi#iduals. - $nfluen ed b! man! onfounding fa tors ex: women ta*ing oral ontra e%ti#e agents, %regnant women, infe tion, leu*emia, m!o ardial infar tion. - 5iurnal #ariation in nonfasting sub>e ts. The highest le#els in nonfasting sub>e t in the morning

- Hormal serum Cu on entration for adults are E0 G 1:0 g3d6 for men - (0 G 1?? g3d6 for women &. Serum !erul"pla m%# !"#!e#$ra$%"# Hot re ommended as an index of Cu status in rossse tional sur#e!/ the on entration in the serum #aries mar*edl! among normal health! indi#iduals '. Cu/(# SOD - "%%roximatel! +0F of the Cu found in @0C is %resent as Cu3;n 9.5. @0C Cu le#els - er! Cu3;n 9.5 le#els or a ti#it! an ser#e as a measure of longterm Cu nutrition

- 70C ha#e shorter turno#er rate - also ontain 9.5. Their use ould %ro#ide information on more re ent Cu inta*e - status. - Dr!. Cu,;n-9.5 a ti#it! is a %arti ularl! sensiti#e index of Cu de%letion. $n an ex%erimental Cu de%letion stud! in male adults, er! Cu, ;n-9.5 a ti#it! was redu ed, des%ite there being no dete table de rease in serum Cu or erulo%lasmin ). O$*er Cu+,epe#,e#$ e#-.me C!to hrome oxidase and l!s!l oxidase /. O$*er mea ure

9e#eral other measures ha#e been in#estigated but ha#e not been onsidered useful or reliable. The! in lude Cu on entration in urine, sweat, sali#a - hair COPPER TO0ICITY - Cu inta*e of 10 to 1? mg an result in metalli state, diarrhea - #omitting - 9e#ere Cu inta*es ma! result in intra#as ular hemol!sis, >aundi e, renal failure, #as ular olla%se death - Most instan es of Cu toxi it! ha#e been related to en#ironmental ex%osure, in luding a indental inges-

tion of Cu 2b! hildren4, water - foods %re%ared or stored in o%%er #essels - industrial ex%osures to Cu