L3 Hb,Mb,enzs

Question 1

LO2: contrast O bind props Mb and Hb, expl why Hb most suited to role as O carrier.

Answer 1

-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.

Question 2

LO3: desc maj struc diffs btw oxy and deoxy Hb and molec basis of coop. T and R.

Answer 2

• 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.

Question 3

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

Answer 3

• 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.

Question 4

LO5: mut in globin genes can=dis eg sickle cell anaem/thalassaemia. molec basis.

Answer 4

• 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.

Question 5

LO1: expl phys roles Mb and Hb.

Answer 5

• transp O, non pol so not diss. Mb in nusc, acc O from Hb. Hb carry co2 to lungs.
• O binds heam grp= protoporphyrin ring, fe centre. fe bound cov to Hb/Mb prot via histid on other side of ring to O.