Flashcards in L3 Hb,Mb,enzs Deck (5)
LO2: contrast O bind props Mb and Hb, expl why Hb most suited to role as O carrier.
-Mb struc- 153 aa, compact, 75% alpha helic, His on 8th alpha helix linked to fe, haem unit centre, sing su prot, can bind 1 O2.
upon O bind- deoxy Fe slight below plane, O bind=move into plane= move His F8 and small change on conf, less imp than in Hb!
hyperbol dep on [O]. constant affin. incr ppO= incr %sat Mb.
- Hb sigm chars, low pp= rel low affin, most in T state. incr pp= incr affin R. O bind incrs affin.
2 alpha chains 141 aa, 2 beta 146. tetramer. each chain heam prosthet grp. each pp aa seq simil Mb.
O bind- deoxy can be low affin T or high affin R state. O bind proms stabil of R. R rotated 15 deg so diff interacs, holds in R. haem grp more exposed.
LO3: desc maj struc diffs btw oxy and deoxy Hb and molec basis of coop. T and R.
- O bind= ferrous to centre, in Hb this pulls rest su, eff whole molec, proms R.
- coop- 1 bind proms subseq. sigm effic lung to tiss. more sensit to small diff in [O]. low in tiss=Hb likely give up O, decr sat. high in lung= prom bind to Hb, sat. su's coop. pick up 2x more in lung than if no coop.
LO4: eff co2, H+, 2'3'-bisphosphoglycerate, and CO on bind O by Hb and physiol sig.
- allost activs shift curve L enhance/stabil R. inhibs shift R, enhance T, decr affin
- BPG 5mM RBC. bi prod glycol. Hb wo BPG=main hyperbol, shift L. with BPG= R, lower affin. allost inhib. occs normally! neg P ionic interac pos grps in beta su. too high affin otherwise. in altit BPG incr allow transp more O to tiss.
-CO2 and H+- bind Hb decr affin. BOHR. prod of metab. coup deliv to demand.
-CO- combs ferroHb and Mb blocks O transp. binds 250x more readilt than O. fatal when COHb over 50%. it incr affin for O in unaff su's. anaemic can have 50% blocked, others change to R but that decr rel in tiss.
LO5: mut in globin genes can=dis eg sickle cell anaem/thalassaemia. molec basis.
- ad 90% HbA alpha2 beta2. Some HbF has gamma2, HbA2 delta2. glycosylat= HbA1C marker for diab. chrom 16 alpha 1 and 2. chrom 11 beta globin like genes.
alpha lot at birth. gamma as foetus, off when born. foetal main HbF higher affin than mat HbA.
-sickle- glu to val in bta glob (HbS). neg acidic to neut npol. glu norm surf su but val phob so beta clust to excl water, form chains, bind cell mem= rigis so cant bend through capills. block=pain, lyse=anaem. sticky phob pock allows deoxy HbS polymerise.
-thalass- imbal no alpha and beta chains. prod more/ deg one faster.
beta: decr or absent beta glob chain prod. norm 2 alleles. minor= 1 copy miss, maj=both. excess alpha cant form stab func tetram, some join and precip out. symps after birth. Barts when gamma only.
alpha: same. each chrom 2 copies so 4 alleles. sev diff levs dis. excess beta can form stab tetram, some precip, some bind O v high affin so not rel in tiss. onset bef birth.