Heme yog porphyrin, nyob rau hauv nruab nrab ntawm cov molecule uas muaj hlau ions Fe2+, uas muaj nyob rau hauv cov qauv los ntawm ob covalent thiab ob qho kev sib koom tes bonds. Porphyrins yog ib qhov system ntawm plaub fused pyrroles uas muaj methylene compounds (-CH=).
Lub heme molecule muaj cov qauv tiaj tus. Cov txheej txheem oxidation converts heme rau hauv hematin, xaiv Fe3+.
Siv gems
Heme yog ib pab pawg prostatic ntawm tsis yog hemoglobin thiab nws cov derivatives, tab sis kuj myoglobin, catalase, peroxidase, cytochromes, tryptophan pyrollase enzyme, uas catalyzes oxidation ntawm troptophan rau formylkynurenine. Muaj peb tus thawj coj hauv gemma cov ntsiab lus:
- erythrocytes, suav nrog hemoglobin;
- cov leeg nqaij uas muaj myoglobin;
- kab mob siab nrog cytochrome P450.
Nyob ntawm kev ua haujlwm ntawm cov hlwb, hom protein hloov pauv, nrog rau porphyrin hauv heme. Hemoglobin heme suav nrog protoporphyrin IX, thiab cytochrome oxidase muaj formylporphyrin.
Home is formed?
Protein ntau lawm tshwm sim nyob rau hauv tag nrho cov ntaub so ntswg ntawm lub cev, tab sis lub feem ntau tsim heme synthesis tshwm sim nyob rau hauv ob lub cev:
- pob txha pob txha tsim cov khoom tsis muaj protein ntau rau kev tsim cov hemoglobin;
- hepatocytes tsim cov ntaub ntawv raw rau cytochrome P450.
Nyob hauv mitochondrial matrix, pyridoxal-dependent enzyme aminolevulinate synthase yog ib qho catalyst rau kev tsim ntawm 5-aminolevulinic acid (5-ALA). Nyob rau theem no, glycine thiab sucinyl-CoA, ib yam khoom ntawm Krebs lub voj voog, koom nrog hauv kev sib txuas ntawm heme. Heme inhibits qhov tshuaj tiv thaiv no. Hlau, ntawm qhov tsis sib xws, ua rau cov tshuaj tiv thaiv hauv reticulocytes nrog kev pab los ntawm kev khi cov protein. Nrog rau qhov tsis muaj pyridoxal phosphate, cov haujlwm ntawm aminolevulinate synthase txo qis. Corticosteroids, non-steroidal anti-inflammatory tshuaj, barbiturates thiab sulfonamides yog stimulants ntawm aminolevulinate synthase. Cov tshuaj tiv thaiv yog tshwm sim los ntawm kev nce hauv kev noj heme los ntawm cytochrome P450 rau kev tsim cov tshuaj no los ntawm lub siab.
5-aminolevulinic acid, lossis porphobilinogen synthase, nkag mus rau cytoplasm los ntawm mitochondria. Qhov no cytoplasmic enzyme muaj, ntxiv rau cov porphobilinogen molecule, ob tug ntxiv molecules ntawm 5-aminolevulinic acid. Thaum lub sij hawm heme synthesis, cov tshuaj tiv thaiv yog inhibited los ntawm heme thiab lead ions. Yog vim li cas thiaj li nce qib hauv cov zis thiab cov ntshav ntawm 5-aminolevulinic acid txhais tau tias ua rau lom lom.
Deamination ntawm plaub molecules ntawm porphybilinogen los ntawm porphobilinogen deaminase rau hydroxymethylbilane tshwm sim hauv cytoplasm. Tsis tas li ntawd, cov molecule tuaj yeem tig mus rau hauv upoporphyrinogen I thiab decarboxylate rau hauv coproporphyrinogen I. Uroporphyrinogen III tau txais los ntawm cov txheej txheem ntawm lub cev qhuav dej ntawm hydroxymethylbilane siv cosynthase enzyme ntawm no.molecules.
Decarboxylation ntawm uroporphyrinogen rau coproporphyrinogen III txuas ntxiv hauv cytoplasm ntxiv rov qab mus rau mitochondria ntawm cov hlwb. Nyob rau tib lub sijhawm, coproporphyrinogen III oxidase decarboxylates molecules ntawm protoporphyrinogen IV (+ O2, -2CO2) los ntawm kev ntxiv oxidation (-6H +) rau protoporphyrin V nrog kev pab ntawm protoporphyrin oxidase. Kev koom ua ke ntawm Fe2 + nyob rau theem kawg ntawm ferrochelatase enzyme rau hauv protoporphyrin V molecule ua tiav heme synthesis. Hlau los ntawm ferritin.
Ntawm ntawm hemoglobin synthesis
Kev tsim cov hemoglobin yog tsim cov heme thiab globin:
- heme yog hais txog cov pab pawg kws kho hniav uas kho qhov rov qab khi ntawm cov pa oxygen rau hemoglobin;
- globin yog cov protein uas nyob ib puag ncig thiab tiv thaiv heme molecule.
Hauv heme synthesis, enzyme ferrochelatase ntxiv cov hlau rau lub nplhaib ntawm protoporphyrin IX qauv los tsim heme, qib qis uas cuam tshuam nrog ntshav ntshav. Hlau deficiency, raws li feem ntau ua rau anemia, txo heme ntau lawm thiab dua txo cov theem ntawm hemoglobin nyob rau hauv cov ntshav.
Ib tus naj npawb ntawm cov tshuaj thiab cov co toxins ncaj qha thaiv heme synthesis, tiv thaiv cov enzymes los ntawm kev koom nrog hauv nws cov biosynthesis. Tshuaj inhibition ntawm synthesis muaj ntau nyob rau hauv cov me nyuam.
Globin formation
Ob qhov sib txawv globin chains (txhua tus nrog nws tus kheej heme molecule) ua ke los tsim hemoglobin. Hauv thawj lub lim tiam ntawm embryogenesis, alpha saw txuas nrog gamma saw. Tom qab yug me nyuam, kev sib koom ua ketshwm sim nrog beta saw. Nws yog kev sib xyaw ua ke ntawm ob txoj hlua alpha thiab ob qho tib si uas ua kom tiav hemoglobin molecule.
Kev sib xyaw ntawm alpha thiab gamma chains tsim cov fetal hemoglobin. Kev sib xyaw ntawm ob alpha thiab ob beta chains muab "tus neeg laus" hemoglobin, uas muaj nyob hauv cov ntshav rau 18-24 lub lis piam txij thaum yug los.
Kev sib txuas ntawm ob txoj hlua sib txuas ua ib qho dimer - ib qho qauv uas tsis thauj cov pa oxygen zoo. Ob lub dimers tsim ib qho tetramer, uas yog daim ntawv ua haujlwm ntawm hemoglobin. Lub complex ntawm biophysical yam ntxwv tswj cov uptake ntawm oxygen los ntawm lub ntsws thiab nws tso tawm nyob rau hauv cov ntaub so ntswg.
Genetic mechanisms
Genes encoding alpha globin chains nyob ntawm chromosome 16, thiab tsis yog alpha chains - ntawm chromosome 11. Raws li, lawv hu ua "alpha globin locus" thiab "beta globin locus". Cov kab lus ntawm ob pawg ntawm cov noob tau zoo sib npaug rau kev ua haujlwm ntawm erythrocyte. Kev tsis txaus ntseeg ua rau muaj kev loj hlob ntawm thalassemia.
Txhua chromosome 16 muaj ob hom alpha globin uas zoo ib yam. Txij li thaum txhua lub cell muaj ob lub chromosomes, plaub ntawm cov noob no ib txwm muaj. Txhua tus tsim ib lub hlis twg ntawm globin alpha chains xav tau rau hemoglobin synthesis.
Cov noob ntawm beta-globin locus ntawm lub chaw nyob yog nyob ua ntu zus, pib ntawm qhov chaw nquag thaum lub sij hawm embryonic txoj kev loj hlob. Cov kab ke yog raws li nram no: epsilon gamma, delta thiab beta. Muaj ob daim ntawv theej ntawm gamma geneTxhua chromosome 11, thiab cov seem muaj nyob rau hauv ib daim ntawv luam. Txhua lub xovtooj ntawm tes muaj ob lub noob beta globin, qhia txog cov protein ntau uas haum txhua tus ntawm plaub alpha globin noob.
YHemoglobin transformation
Txoj kev ntsuas ntsuas ntawm qib caj ces tseem tsis paub txog tshuaj. Ib qho tseem ceeb ntawm tus menyuam hauv plab hemoglobin khaws cia hauv lub cev ntawm tus menyuam rau 7 - 8 lub hlis tom qab yug menyuam. Feem ntau cov tib neeg tsuas muaj cov lej xwb, yog tias muaj, ntawm tus menyuam hauv plab hemoglobin tom qab menyuam mos.
Kev sib xyaw ntawm ob alpha thiab beta noob ua rau cov neeg laus hemoglobin A. Cov noob delta, nyob nruab nrab ntawm gamma thiab beta ntawm chromosome 11, tsim cov delta globin me me hauv cov menyuam yaus thiab cov neeg laus - hemoglobin A2, uas tsawg dua. tshaj 3% squirrel.
ALK ratio
Tus nqi ntawm heme tsim yog cuam tshuam los ntawm kev tsim cov aminolevulinic acid, lossis ALA. Lub synthase uas pib cov txheej txheem no yog tswj nyob rau hauv ob txoj kev:
- allosterically nrog kev pab los ntawm effector enzymes uas tau tsim thaum lub sij hawm cov tshuaj tiv thaiv nws tus kheej;
- ntawm qib caj ces ntawm kev tsim cov enzyme.
Kev sib txuas ntawm heme thiab hemoglobin inhibits kev tsim cov aminolivulinate synthase, tsim cov lus tsis zoo. Cov tshuaj steroids, cov tshuaj uas tsis yog-steroidal anti-inflammatory, tshuaj tua kab mob sulfonamides txhawb kev tsim cov synthase. Tawm tsam keeb kwm yav dhau los ntawm kev noj tshuaj, kev nce ntawm heme nyob rau hauv cytochrome P450 system, uas yog ib qho tseem ceeb rau kev tsim cov tshuaj no los ntawm lub siab, nce.
Heme production factor
NyobKev tswj hwm ntawm heme synthesis los ntawm qib ntawm ALA synthase yog cuam tshuam los ntawm lwm yam. Glucose slows tus txheej txheem ntawm ALA synthase kev ua. Tus nqi ntawm cov hlau hauv cell cuam tshuam rau kev sib txuas ntawm qib ntawm kev txhais lus.
MRNA muaj lub voj plaub hau ntawm qhov chaw pib txhais lus - lub ntsiab lus hlau-rhiab. Kev txo qis hauv qib ntawm cov hlau synthesis nres, nyob rau theem siab, cov protein cuam tshuam nrog cov hlau, cysteine thiab inorganic sulfur, uas ua tiav qhov sib npaug ntawm kev tsim cov heme thiab ALA.
Synthesis disorders
Kev ua txhaum hauv cov txheej txheem ntawm heme synthesis ntawm biochemistry yog qhia nyob rau hauv ib qho tsis txaus ntawm ib qho ntawm cov enzymes. Qhov tshwm sim yog kev loj hlob ntawm porphyria. Daim ntawv keeb kwm ntawm tus kab mob no cuam tshuam nrog kev mob caj ces, thaum daim ntawv tau txais kev txhim kho nyob rau hauv kev cuam tshuam ntawm cov tshuaj lom thiab ntsev ntawm cov hlau hnyav.
Cov enzyme deficiency tau tshwm sim hauv daim siab lossis erythrocytes, uas cuam tshuam rau lub ntsiab lus ntawm pawg porphyria - kab mob siab lossis erythropoietic. Tus kab mob tuaj yeem tshwm sim hauv cov mob hnyav lossis mob ntev.
Kev cuam tshuam hauv heme synthesis yog txuam nrog cov khoom sib txuas ntawm cov khoom nruab nrab - porphyrinogens, uas yog oxidized. Qhov chaw ntawm tsub zuj zuj nyob ntawm localization - nyob rau hauv erythrocytes los yog hepatocytes. Qib ntawm tsub zuj zuj ntawm cov khoom yog siv los kuaj porphyria.
Toxic porphyrinogens tuaj yeem ua rau:
- neuropsychiatric mob;
- daim tawv nqaij mob vim photosensitivity;
- cuam tshuam ntawm reticuloendothelial system ntawm daim siab.
Cov zis hloov ntshav nrog cov porphyrins ntau dhauntxoov ntxoo. Ib qho dhau ntawm aminolevulinate synthase nyob rau hauv kev cuam tshuam ntawm cov tshuaj lossis kev tsim cov tshuaj steroid thaum lub hnub nyoog hluas tuaj yeem ua rau muaj tus kab mob hnyav dua.
Porphyria hom
Tus mob porphyria cuam tshuam nrog qhov tsis xws luag hauv cov noob uas sau rau deaminase thiab ua rau 5-ALA thiab porphobilinogen tsub zuj zuj. Cov tsos mob yog cov zis tsaus, paresis ntawm cov leeg ua pa, lub plawv tsis ua haujlwm. Tus neeg mob yws ntawm qhov mob plab, cem quav, ntuav. Tus kab mob tuaj yeem tshwm sim los ntawm kev noj tshuaj analgesics thiab tshuaj tua kab mob.
Congenital erythropoietic porphyria yog txuam nrog qis uroporphyrinogen-III-cosynthase kev ua haujlwm thiab qib siab ntawm uroporphyrinogen-I-synthase. Cov tsos mob yog photosensitivity, uas yog manifested los ntawm tej kab nrib pleb nyob rau hauv daim tawv nqaij, bruising.
Hereditary coproporphyria yog txuam nrog qhov tsis muaj coproporphyrinogen oxidase, uas koom nrog kev hloov pauv ntawm coproporphyrinogen III. Yog li ntawd, lub enzyme yog oxidized nyob rau hauv lub teeb rau coproporphyrin. Cov neeg mob raug kev txom nyem los ntawm lub plawv tsis ua hauj lwm thiab photosensitivity.
Mosaic porphyria yog ib qho teeb meem nyob rau hauv uas muaj ib feem ntawm cov enzymatic hloov dua siab tshiab ntawm protoporphyrinogen rau heme. Cov cim qhia yog cov zis fluorescence thiab rhiab heev rau lub teeb.
Tardor cutaneous porphyria tshwm nrog lub siab puas tsuaj rau keeb kwm ntawm cawv thiab ntau hlau. Cov concentrations siab ntawm hom I thiab III uroporphyrins raug tso tawm hauv cov zis, muab cov xim pinkish thiab ua rau fluorescence.
Erythropoietic protoporphyria yog provoked los ntawm qisferrochelatase enzyme kev ua hauv mitochondria, ib qhov chaw ntawm hlau rau heme synthesis. Cov tsos mob yog mob urticaria nyob rau hauv kev cuam tshuam ntawm ultraviolet hluav taws xob. Cov qib siab ntawm protoporphyrin IX tshwm sim hauv erythrocytes, ntshav thiab quav. Cov qe ntshav liab tsis paub qab hau thiab tawv nqaij feem ntau fluoresce nrog lub teeb liab.
