ENZYMES OF CLINICAL SIGNIFICANCE Creatine Kinase (CK) Characteristics Its molecular weight is approximately 82,000.

It is a dimer comprised of two subu its the !, or brai subu it, a d the ", or muscle subu it), #his results i three CK isoe $ymes. i. CK%!! (CK&) isoe $yme , (brai type) ii. CK%"! (CK2) isoe $yme, (hybrid type) iii. CK%"" (CK') isoe $yme, (muscle type) ( electrophoretic separatio ) CK%!! will migrate fastest toward the a ode a d is therefore called CK-1. CK%!! is followed by CK%"! (CK%2), a d, fi ally, by CK "" (CK%' which exhibits the slowest mobility (. It is ge erally associated with *#+ rege eratio i co tractile or tra sport systems. Its predomi a t physiologic fu ctio occurs i muscle cells, where it is i ,ol,ed i the storage of high e ergy creati e phosphate. -,ery co tractio cycle of muscle results i creati e phosphate use. #his is accompa ied with the productio of *#+ by CK reactio #his results i relati,ely co sta t le,els of muscle *#+. #he re,ersible reactio cataly$ed by CK is show i -.uatio &0%/.

Creati e 0 *#+ CK creati e phosphate 0 *1+ Tissue Source Highest acti,ities are fou d i s2eletal muscle heart muscle brai tissue.

Smaller .ua tities are fou d i 2id ey the bladder prostate gastroi testi al tract li,er pa creas splee uterus place ta thyroid lu g . Lactate Dehydr genase 3actate dehydroge ase (31) is a e $yme that cataly$es the i terco ,ersio of lactic a d pyru,ic acids. It is a hydroge %tra sfer e $yme that uses the coe $yme 4*10 . #issue Source 31 is widely distributed i the body. 5igh acti,ities are fou d i the heart, li,er, s2eletal muscle, 2id ey, a d erythrocytes6 lesser amou ts are fou d i the lu g, smooth muscle, a d brai . As!artate Amin trans"erase *spartate ami otra sferase (*7#) is a e $yme belo gi g to the class of tra sferases. It is commo ly referred to as a tra samilase a d is i ,ol,ed i the tra sfer of a ami o group betwee aspartate a d a%2eto acids. #he older termi ology, serum glutamic%oxaloacetic tra sami ase (78(#, or GOT), may also be used. +yridoxal phosphate fu ctio s as a coe $yme. #he tra sami atio reactio is importa t i i termediary metabolism because of its fu ctio i the sy thesis a d degradatio of ami o acids. #he 2etoacids formed by the reactio are ultimately oxidi$ed by the tricarboxylic acid cycle to pro,ide a source of e ergy. #issue Source

*7# is widely distributed i huma tissue. #he highest co ce tratio s are fou d i cardiac tissue, li,er, a d s2eletal muscle, with smaller amou ts fou d i the 2id ey, pa creas, a d erythrocytes. Alanine Amin trans"erase *la i e ami otra sferase (*3#) is a tra sferase with e $ymatic acti,ity similar to *7#. 7pecifically, it cataly$es the tra sfer of a ami o group from ala i e to a2etoglutarate with the formatio of glutamate a d pyru% ,ate. #he older termi ology was serum glutamic%pyru,ic tra sami ase (78+#, or GPT). Tissue Source *3# is distributed i ma y tissues, with comparati,ely high co ce tratio s i the li,er. It is co sidered the more li,er%specific e $yme of the tra sferases. Al#aline $h s!hatase *l2ali e phosphatase (*3+) belo gs to a group of e $ymes that cataly$e the hydrolysis of ,arious phosphomo oesters at a al2ali e p5. Co se.ue tly, *3+ is a o specific e $yme capable of reacti g with ma y differe t substrates. 7pecifically, *3+ fu ctio s to liberate i orga ic phosphate from a orga ic phosphate ester with the co comita t productio of a alcohol. #he optimal p5 for the reactio is 9.0%&0.0, but optimal p5 ,aries with the substrate used. #he e $yme re.uires "g0 as a acti,ator. %iss&e Source *3+ acti,ity is prese t o cell surfaces i most huma tissue. #he highest co ce tratio s are fou d i the i testi e, li,er, bo e, splee , place ta, a d 2id ey. I the li,er, the e $yme is located o both si usoidal a d bile ca alicular membra es6 acti,ity i bo e is co fi ed to the osteoblasts, those cells i ,ol,ed i productio of bo e matrix. #he specific locatio of the e $yme withi this tissue accou ts for the more predomi a t ele,atio s i certai disorders. Acid $h s!hatase *cid phosphatase (*C+) belo gs to the same group of phosphatase e $ymes as *3+ a d is a hydrolase that cataly$es the same type of

reactio s. #he ma:or differe ce betwee *C+ a d *3+ is the p5 of the reactio . *C+ fu ctio s at a optimal p5 of approximately ;.0. %iss&e Source *C+ acti,ity is fou d i the prostate, bo e, li,er, splee , 2id ey, erythrocytes, a d platelets. #he prostate is the richest source, with ma y times the acti,ity fou d i other tissue. '(Gl&tamyltrans"erase ' %8lutamyltra sferase (88#) is a e $yme i ,ol,ed i the tra sfer of the ' %glutamyl residue from ' %glutamyl peptides to ami o acids, 52(, a d other small peptides. I most biologic systems, glutathio e ser,es as the ' glutamyl do or. #he specific physiologic fu ctio of 88# has ot bee clearly established, but it is suggested that 88# is i ,ol,ed i peptide a d protei sy thesis, regulatio of tissue glutathio e le,els, a d the tra sport of ami o acids across cell membra es. #issue Source 88# acti,ity is fou d primarily i tissue of the 2id ey, brai , prostate, pa creas, a d li,er. Cli ical applicatio s of assay, howe,er, are co fi ed mai ly to e,aluatio of li,er a d biliary system disorders. Amylase *mylase (*"7) is a e $yme belo gi g to the class of hydrolases that cataly$e the brea2dow of starch a d glycoge . 7tarch co sists of both amylose a d amylopecti . *mylose is a lo g, u bra ched chai of glucose molecules, li 2ed by < &%/ glycosidic bo ds6 amylopecti is a bra ched% chai polysaccharide with < &%= li 2ages at the bra ch poi ts. #he structure of glycoge is similar to that of amylopecti but is more highly bra ched. <%*"7 attac2s o ly the < &%/ glycosidic bo ds to produce degradatio products co sisti g of glucose6 maltose6 a d i termediate chai s, called dextrins, which co tai < &%= bra chi g li 2ages. Cellulose a d other structural polysaccharides co sisti g of li 2ages are ot attac2ed by <% *"7. *"7 is therefore a importa t e $yme i the physiologic digestio of starches. *"7 re.uires calcium a d chloride io s for its acti,atio .

%iss&e Source #he aci ar cells of the pa creas a d the sali,ary gla ds are the ma:or tissue sources of serum *"7. 3esser co ce tratio s are fou d i s2eletal muscle a d the small i testi e a d fallopia tubes. *"7 is the smallest e $yme, with a molecular weight of ;0,000%;;,000. !ecause of its small si$e, it is readily filtered by the re al glomerulus a d also appears i the uri e. 1igestio of starches begi s i the mouth with the hydrolytic actio of sali,ary *"7. 7ali,ary *"7 acti,ity, howe,er, is of short duratio because, o swallowi g, it is i acti,ated by the acidity of the gastric co te ts. +a creatic *"7 the performs the ma:or digesti,e actio of starches o ce the polysaccharides reach the i testi e. Li!ase 3ipase (3+7) is a e $yme that hydroly$es the ester li 2ages of fats to produce alcohols a d fatty acids. 7pecifically, 3+7 cataly$es the partial hydrolysis of dietary triglycerides i the i testi e to the 2%mo oglyceride i termediate, with the productio of lo g%chai fatty acids. #he e $ymatic acti,ity of pa creatic 3+7 is specific for the fatty acid residues at positio s & a d ' of the triglyceride molecule, but substrate must be a emulsio for acti,ity to occur. #he reactio rate is accelerated by the prese ce of colipase a d a bile salt. Tissue Source 3+7 co ce tratio is fou d primarily i the pa creas, although it is also prese t i the stomach a d small i testi e. Gl&c se()($h s!hate Dehydr genase 8lucose%=%phosphate dehydroge ase (8%=%+1) is a oxidoreductase that cataly$es the oxidatio of glucose =phosphate to =%phosphogluco ate or the correspo di g lacto e. #he reactio is importa t as the first step i the pe tose%phosphate shu t of glucose metabolism with the ultimate productio of 4*1+5. Tissue Source 7ources of 8%=%+1 i clude the adre al cortex, splee , thymus, lymph odes, lactati g mammary gla d, a d erythrocytes. 3ittle acti,ity is fou d i ormal serum.