L5 Regul of prot activ

Question 1

LO1: list maj regul mechs that contr enz activ (and egs).

Answer 1

ST:
-[S] and [P]. isoenz eg GK and HK. some coenz lim avail. accum of prod can comp inhib eg G6P inhib HK.
-allosteric- sigm rate vs [S]. multip su. low affin T state, high R.
allost activs bind outs AS, stabil R, alt conf 1 su=incr bind S, incr affin and rate, shift L. inhibs opp.
PFK!!
-cov modif- post ransl add grps. eg P, acetylat, gamma carboxylat, ubiquitinat, methylat, palmitoylat, myristoylat, ribosyl.
phosphorylat- P from ATP to OH of ser, thr, tyr by kinase. hydrol by phosphatase.
-proteolytic cleav.
LT:
- change rate prot synth or deg.

Question 2

LO2: disc allost props of key regul enz.

Answer 2

-PFK see diags.

Question 3

LO3: disc concept of enz cascs and use PKs and Pases to reg activ.

Answer 3

• amplif sig by sev orders mag in ms. multip kinases activ by Plat.
• glycog breakd recip regul- casc forms enz to breakd glycog. if gluc high want rev make glycog so P glycog synthase.

Question 4

LO4: define zymogen and egs.

Answer 4

• zymog=inactiv prot precurs. activ by rem part pp. so not active in wrong place.
• dig enzs synth as zymog in stom and panc eg pepsinogen to pesin by cleav. panc chymotrypsinogen, trypsinogen, procarboxypeptiase, proelastase.
• some horms eg insulin.
  -blood clott med by casc proteolytic activ= rap and amplif resp.
  -dev procs to contrib to tiss remod.
  -apop prog cell death med by caspases synth as procaspase.
  often master molec eg trypsin
  reg often master molec eg trypsin.

Question 4

LO5: how activat clott casc=format fibrin.

Answer 4

• inrinsic and extrinsic both activ fX. this cleaves prothrombin to active thrmbin 2 chains s-s link. this chops off neg N termin of alpha and beta peps, allows C termin glob doms to interact=aggreg= soft clot non cov elecstat interac, then other cf form cov.
  glutamine + lysine x linked by transglutaminase activ by thrombin, amide bonds btw sc’s.

Question 5

LO6: mechs inv in reg clot form and breakd.

Answer 5

• gla resids- COOH added to glutamine in ER by carboxylase. allows interac with sites of dam- exposed Plip. brings cf’s togeth. ca x bridge btw neg regs on cf.
  -thrombin allost activ- feedb to speed up cofac form. ensures contin clott. enhances activ of fV, fVIII, fXI.
  -stop clott proc by rem activ prots/ proteolytic dig/bind inhibs-
  localisat prothrombin- dilut cf by blood flow, rem by liv. slow.
  dig by protease- eg fVa and VIIIa deg by prot C activ by thrombin.
  -specif inhibs- antithrombin III enhanced by heparin bind. v tight bind thrombin and fX.
  -inactiv zymog at low conc.
• proteolytic activ amplif sig by cas.
• clot breakd contr by proteolytic activ- fibrinolysis by plasmin breaks into frags. plasmin aciv from plasminogen by tiss plasminogen activator, and streptokinase.