Ebook The big picture: Medical biochemistry: Par 1

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CONTENTS
Dedications
Acknowledgements
About the Authors
SECTION I: THE BASIC MOLECULES OF LIFE
CHAPTER 1 Ami no Aci ds a nd Protei ns
Overvi ew
Ami no Aci ds —Structure a nd Functi ona l Groups
Es s enti a l a nd Non-Es s enti a l
Ba s i c Structure
Cha ra cteri s ti cs of R-Groups
Ba s i c Protei n Structure
Level s of Protei n Structure
Ca tegori es of Protei ns
Ami no Aci d a nd Pepti de-Deri ved Hormones a nd Neurotra ns mi tters

Enzymes
Structura l Protei ns
Motor Protei ns
Tra ns port/Cha nnel Protei ns
Revi ew Ques ti ons
CHAPTER 2 Ca rbohydra tes
Overvi ew
Ba s i c Ca rbohydra te Structure a nd Functi on
Monos a ccha ri des a nd Di s a ccha ri des
Gl ycogen a nd Sta rches
Gl ycoprotei ns
Gl ycos a mi nogl yca ns
Revi ew Ques ti ons
CHAPTER 3 Li pi ds
Overvi ew
Ba s i c Li pi d Functi ons
Ba s i c Membra ne Li pi d Structure
Compl ex Li pi ds
Gl ycol i pi ds /Sphi ngol i pi ds
Ei cos a noi ds
Chol es terol
Li poprotei ns
Bi l e Sa l ts
Li pi d-Deri ved Hormones /Vi ta mi n D
Corti cos teroi ds (Adrena l Gl a nd)
Androgens (Tes tes ) a nd Es trogens (Ova ri es )
Vi ta mi n D
Revi ew Ques ti ons
CHAPTER 4 Nucl eos i des , Nucl eoti des , DNA, a nd RNA
Overvi ew

Nucl eos i des a nd Nucl eoti des
Components of Nucl eos i des a nd Nucl eoti des
Synthes i s of Puri ne Nucl eos i des a nd Nucl eoti des
Synthes i s of Pyri mi di ne Nucl eos i des a nd Nucl eoti des
Forma ti on of Deoxy Nucl eos i des a nd Nucl eoti des
Brea kdown of Puri nes a nd Pyri mi di nes
RNA a nd DNA—Ba s i c Structure a nd Functi on
RNA
DNA
Revi ew Ques ti ons
SECTION I: Integra ted USMLE-Styl e Ques ti ons a nd Ans wers
Ques ti ons
Ans wers


SECTION II: FUNCTIONAL BIOCHEMISTRY
CHAPTER 5 Enzymes a nd Ami no Aci d/Protei n Meta bol i s m
Overvi ew
Enzymes
Enzyme Rea cti ons
Cofa ctors
Regul a ti on
Ami no Aci d Meta bol i s m
Ami no Aci d Synthes i s
Ami no Aci d Degra da ti on
The Urea Cycl e
Revi ew Ques ti ons
CHAPTER 6 Ca rbohydra te Meta bol i s m
Overvi ew
Gl ycol ys i s

Ci tri c Aci d Cycl e
Oxi da ti ve Phos phoryl a ti on
Gl uconeogenes i s
The Pentos e Phos pha te Pa thwa y
Gl ycogen Synthes i s
Gl ycogen Brea kdown
Modi fi ed Ca rbohydra tes (Gl ycoprotei ns , GAGs )
Revi ew Ques ti ons
CHAPTER 7 Li pi d Meta bol i s m
Overvi ew
Fa tty Aci d Meta bol i s m
Fa tty Aci d Synthes i s
Fa tty Aci d Degra da ti on
Meta bol i s m of Compl ex Li pi ds
Tri a cyl gl ycerol Synthes i s
Phos phogl yceri de Synthes i s
Ketone Body Synthes i s
Cera mi de/Sphi ngol i pi ds Synthes i s
Chol es terol Synthes i s
Revi ew Ques ti ons
CHAPTER 8 Membra nes
Overvi ew
Membra ne Structure
Li pi ds
Protei ns
Membra ne Functi ons
Membra ne Cha nnel s
Membra ne Si gna l i ng
Revi ew Ques ti ons
CHAPTER 9 DNA/RNA Functi on a nd Protei n Synthes i s

Overvi ew
Structure of the Nucl eus
Hi s tones
Nucl ea r Ma tri x/Sca ffol d
Nucl eol us a nd Ri bos ome Synthes i s
DNA Repl i ca ti on a nd Tra ns cri pti on
DNA Repl i ca ti on
Tra ns cri pti on
Protei n Synthes i s
Pos ttra ns l a ti ona l Tra ffi cki ng/Modi fi ca ti on
Control of Gene Expres s i on
Muta ti ons a nd Repa i r Mecha ni s ms
Regul a ti on of Cel l Growth a nd Di fferenti a ti on
Revi ew Ques ti ons
SECTION II: Integra ted USMLE-Styl e Ques ti ons a nd Ans wers
Ques ti ons


Ans wers
SECTION III: APPLIED BIOCHEMISTRY
CHAPTER 10 Meta bol i s m a nd Vi ta mi ns /Mi nera l s
Co-authors/Editors: Maria L. Valencik and Cynthia C. Mastick
Overvi ew
Meta bol i c Rol es of Ma jor Bi ochemi ca l Mol ecul es
Integra ti on a nd Regul a ti on of Meta bol i s m
Gl ucos e-6-phos pha te
Pyruva te
Acetyl -CoA
Hormona l Control of Meta bol i s m
Ins ul i n

Gl uca gon
Ca techol a mi nes
Gl ucocorti coi ds
Di a betes Mel l i tus (DM)
Vi ta mi ns a nd Mi nera l s
Vi ta mi ns
Mi nera l s
Revi ew Ques ti ons
CHAPTER 11 The Di ges ti ve Sys tem
Editor: Kshama Jaiswal
Overvi ew
Summa ry of the Di ges ti ve Sys tem
Mouth
Stoma ch
Li ver
Li pi d Meta bol i s m i n the Li ver
Ga l l Bl a dder
Pa ncrea s
Sma l l Intes ti ne (Duodenum, Jejunum, a nd Il eum)
La rge Intes ti ne/Anus
Revi ew Ques ti ons
CHAPTER 12 Mus cl es a nd Moti l i ty
Co-author/Editor: Darren Campbell
Overvi ew
The Ba s i c Components of Mus cl e
Acti n
Tropomyos i n–Troponi ns
Myos i n
Myos i n Li ght Cha i ns
Acti n-Bi ndi ng Protei ns

Exci ta ti on–Contra cti on Coupl i ng
Skel eta l Mus cl e
Structure a nd Genera l Overvi ew
Skel eta l Mus cl e Types
Ca rdi a c Mus cl e
Smooth Mus cl e
Energy Producti on a nd Us e i n Mus cl es
Mi crotubul e-Ba s ed Moti l i ty
Intermedi a te Fi l a ments
Nonmus cl e Cel l s
Revi ew Ques ti ons
CHAPTER 13 Connecti ve Ti s s ue a nd Bone
Editor: Jacques Kerr, BSc, MB, BS, FRCS, FCEM
Overvi ew
Connecti ve Ti s s ue
Components of Bone
Bone Growth a nd Remodel i ng
Regul a ti on of Ca l ci um Level s


Ma rkers of Bone Forma ti on a nd Res orpti on
Revi ew Ques ti ons
CHAPTER 14 Bl ood
Co-authors/Editors: Matthew Porteus, MD, PhD and Tina Mantanona
Overvi ew
Ba s i c Components of Bl ood
Red Bl ood Cel l (RBC) Functi ons
Di s ea s es As s oci a ted wi th Ina dequa te Synthes i s of Hemogl obi n Components
Oxygen Bi ndi ng
Tens e a nd Rel a xed Hgb

Al l os teri c Bi ndi ng of O2 by Hgb
Regul a ti on of O2 Bi ndi ng
Phys i ol ogi c Res pons e to Ina dequa te O2 Del i very
Si ckl e Cel l Di s ea s e (SCD)
Iron
Iron Meta bol i s m
Tra ns ferri n
Ferri ti n
Regul a ti on of Iron Ava i l a bi l i ty by Hepci di n
Cl otti ng
Pl a tel et Pl ug Forma ti on Cons i s ts of Adhes i on, Aggrega ti on, a nd Acti va ti on of Pl a tel ets
The Cl otti ng Ca s ca de
The Fi bri n Mes hwork
Di fference between Pl a tel et Pl ug Forma ti on a nd Cl ot Forma ti on
Regul a ti on of Cl ot Forma ti on
Pl a s mi n a nd Cl ot Di s s ol uti on
Revi ew Ques ti ons
CHAPTER 15 The Immune Sys tem
Editor: Eric L. Greidinger, MD
Overvi ew
Overvi ew of the Immune Sys tem
Anti gen
Anti body
Cel l s As s oci a ted wi th the Immune Sys tem
T Lymphocytes
B Lymphocytes /Pl a s ma Cel l s
Na tura l Ki l l er (NK) Cel l s
Monocytes a nd Ma cropha ges
Neutrophi l s
Eos i nophi l s

Ba s ophi l s
Dendri ti c Cel l s (DCs )
Cytoki nes
Inna te Immuni ty
Compl ement s ys tem
Hypers ens i ti vi ty Rea cti ons
Revi ew Ques ti ons
CHAPTER 16 The Ca rdi ova s cul a r Sys tem
Editor: Ralph V. Shohet, MD
Overvi ew
Ca rdi a c Mus cl e Structure a nd Functi on
Si noa tri a l a nd Atri oventri cul a r Nodes
The Ca rdi a c Cycl e
Bl ood Ves s el s
Endogenous Chol es terol /Li poprotei n Meta bol i s m a nd Tra ns port
VLDL
Intermedi a te-Dens i ty Li poprotei n (IDL) a nd LDL
HDL
Atheros cl eros i s
Bi ochemi ca l Mecha ni s ms As s oci a ted wi th Hea rt Atta ck
Revi ew Ques ti ons


CHAPTER 17 The Res pi ra tory Sys tem
Editor: Howard J. Huang, MD
Overvi ew
Ba s i c Ana tomy a nd Devel opment
Pul mona ry Surfa cta nt a nd the Devel opi ng Lung
O2 –CO2 Excha nge i n the Lung a nd Aci d–Ba s e Ba l a nce
Noni nfecti ve Di s ea s es of the Res pi ra tory Sys tem

Obs tructi ve Di s ea s es —Emphys ema
Obs tructi ve Di s ea s es —Bronchi ti s
Obs tructi ve Di s ea s es —As thma
Bi ochemi ca l Ba s i s of As thma Medi ca ti ons
Res tri cti ve Di s ea s es —Acute Res pi ra tory Di s ea s e Syndrome
Res tri cti ve Di s ea s es —Occupa ti ona l Expos ures
Res tri cti ve Di s ea s es —Inters ti ti a l Lung Di s ea s es
Infecti ve Di s ea s es of the Res pi ra tory Sys tem
Revi ew Ques ti ons
CHAPTER 18 The Uri na ry Sys tem
Editor: Armando J. Lorenzo, MD, MSc, FRCSC, FAAP Overvi ew
Ba s i c Ana tomy a nd Phys i ol ogy
Rena l Fi l tra ti on
The Rena l Corpus cl e
Nephron
Inul i n/Crea ti ni ne Cl ea ra nce
Reni n–Angi otens i n–Al dos terone Sys tem (RAAS)
Reni n a nd Bl ood Pres s ure
Ma cul a Dens a a nd Bl ood Fl ow/Os mol a ri ty
Angi otens i nogen/Angi otens i n I a nd II
Al dos terone
Va s opres s i n
Atri a l Na tri ureti c Pepti de (ANP)
Aci d–Ba s e Ba l a nce
NH 3 a nd Aci d–Ba s e Ba l a nce
Syntheti c Functi ons
Synthes i s of Erythropoi eti n
Rol e i n Vi ta mi n D Synthes i s
Revi ew Ques ti ons
CHAPTER 19 The Nervous Sys tem

Editor: Kathryn Beck-Yoo, MD
Overvi ew
Components of the Nervous Sys tem
Nerve Impul s e Conducti on
Neuron a t Res t
Nerve Impul s e
Repol a ri za ti on
Autonomi c Nervous Sys tem
Sympa theti c Nervous Sys tem
Pa ra s ympa theti c Nervous Sys tem
Neurotra ns mi tters
Dopa mi ne
NE/Epi nephri ne
Serotoni n
Acetyl chol i ne (Ach)
Regul a ti on of Ca techol a mi nes
Gl yci ne, Gl uta ma te, a nd GABA
Neuropepti des
Bi ochemi s try of Vi s i on
Anes thes i a
Revi ew Ques ti ons
CHAPTER 20 The Reproducti ve Sys tem
Editor: Catrina Bubier, MD
Overvi ew


Ba s i c Ana tomy a nd Devel opment
Fema l e Reproducti ve Sys tem
GnRH
FSH

LH
Es trogens
Proges terone
hCG
The Mens trua l Cycl e
Mens trua ti on (Da ys 1–4)
Fol l i cul a r/Prol i fera ti ve Pha s e (Da ys 5–13)
The Lutea l /Secretory Pha s e (Da ys 15–28)
Ferti l i za ti on
Brea s t Devel opment a nd La cta ti on
Oxytoci n
Prol a cti n
Ma l e Reproducti ve Sys tem
Tes tos terone
FSH a nd LH
Revi ew Ques ti ons
SECTION III: Integra ted USMLE-Styl e Ques ti ons a nd Ans wers
Ques ti ons
Ans wers
SECTION IV: APPENDICES
APPENDIX I: Bi ochemi ca l Ba s i s of Di s ea s es
Contributing Editor: Harold Cross, MD, PhD
Ami no Aci d Synthes i s /Degra da ti on
Ami no Aci d Tra ns port
Urea Cycl e Di s orders
Structura l Protei ns
Ca rbohydra tes
Gl ycogen Stora ge
Mi tochondri a l Enzymes (Excl udi ng Urea Cycl e a nd Fa tty Aci d Oxi da ti on)
Li pi ds a nd Fa tty Aci d Oxi da ti on Errors

Nucl eoti de Meta bol i s m
Defecti ve DNA
Bi l i rubi n Meta bol i s m
Bl ood Cl otti ng Fa ctor Defects
Steroi d Hormone Synthes i s
Vi ta mi ns /Mi nera l s a nd El ectrol ytes
APPENDIX II: Bi ochemi ca l Methods
Pol ya cryl a mi de Gel El ectrophores i s (PAGE) [Sodi um Dodecyl Sul fa te (SDS)/Non-SDS]
Immunoa s s a ys
RIA
ELISA or EIA
Chroma togra phy
Thi n La yer (Pa per) Chroma togra phy (TLC)
Col umn Chroma togra phy
Gel Fi l tra ti on Chroma togra phy
Ion-Excha nge Chroma togra phy
Affi ni ty Chroma togra phy
Hi gh-Performa nce/Pres s ure Li qui d Chroma togra phy (HPLC)
Protei n a nd Deoxyri bonucl ei c Aci d (DNA)/Ri bonucl ei c Aci d (RNA) Preci pi ta ti on
DNA a nd RNA Sequenci ng
Southern, Northern, a nd Wes tern Bl ots
Southern Bl otti ng
Northern Bl otti ng
Wes tern Bl otti ng
PCR
Cl oni ng


Fl ow Cytometry
La bora tori es

APPENDIX III: Orga ni c Chemi s try Pri mer
Overvi ew
Introducti on
The Si x Orga ni c El ements (C, H, N, O, P, a nd S)
Ca rbon (C)
Hydrogen (H)
Ni trogen (N)
Oxygen (O)
Phos phorus (P)
Sul fur (S)
Bi ochemi ca l Functi ona l Groups (H, OH, COOH, NH 3 , PO3 , S—S, COH, a nd
+

Hydrogen (Pa rti a l l y Cha rged a nd Ioni c Forms , H )
Hydroxyl Group (—OH −)
Ca rboxyl Group (—COOH)
Ami ne Group (—NH 2 )
Phos pha te Group (PO3 a nd PO4 )
Sul fur–Sul fur Bonds (—S—S—)
Al dehyde Group (—COH)
Ketone (—
Summa ry
Index

)

)


DEDICATIONS

To my fa mi l y: my dea r wi fe, Meryl , who ha s unfa i l i ngl y s upported my profes s i ona l endea vors a nd endured my countl es s eveni ng hours a t the
computer on thi s project; my da ughters , Rebecca , La ura , a nd Mi ri a m, who bri ng me i ncredi bl e “na ches ”; my mother a nd fa ther (ma y they res t i n
pea ce) for thei r s upport i n my forma ti ve yea rs ; my brothers Howa rd a nd Ma tthew; my mother-i n-l a w Ma rtha for her ever-pres ent a ccol a des ; my
fa ther-i n-l a w Ed (ma y he res t i n pea ce); a nd my fa ther-i n-l a w Lou for the profes s i ona l res pect a l wa ys a ccorded me.
Fi na l l y to the more tha n 3000 medi ca l s tudents I ha ve ta ught who i ns pi red my s ucces s a s a tea cher a nd educa tor a nd who preceded thos e
s tudents who I trus t wi l l benefi t from thi s textbook
— Ma rc E. Ti s chl er
To my pa rents , fa mi l y, a nd fri ends who pers evered throughout the wri ti ng, proofi ng, a nd publ i ca ti on of thi s book a s wel l a s the ma ny
i ns tructors , from hi gh s chool to uni vers i ty to gra dua te s chool to medi ca l s chool a nd beyond, who i ns ti l l ed i n me not onl y a l ove for l ea rni ng
but a l s o for tea chi ng.
Thi s book i s pers ona l l y dedi ca ted to one s uch pers on, Ca s s i e Murphy-Cul l en, PhD (ma y s he res t i n pea ce), who s erved a s a tea cher, couns el or
a nd, mos t-of-a l l , cons ta nt a nd dedi ca ted fri end to a l l of her s tudents , i ncl udi ng mys el f.
— Lee W. Ja ns on


ACKNOWLEDGEMENTS
Si ncere tha nks to the current a uthors of Ha rper’s Il l us tra ted Bi ochemi s try for thei r revi ews a nd comments wi th s peci a l tha nks to Dr. Robert
Murra y, edi tor of Ha rper’s , for hi s pa ti ence, ki ndnes s , a nd excepti ona l efforts i n revi ewi ng thi s book. The a uthors a l s o wi s h to tha nk Andrea
Agui rre, Chi neyne Ana ko, Ma rti n Benja mi n, Na ta s ha Bhuya n, Jos eph Ca rrol l , Ka tha ri ne Fl a nnery, Si l vi ja Gottes ma n, Mi cha el Ori , Cha rl es
Ra ppa port, Chri s topher Ri l ey, Al a n Schuma cher, a nd Ka ren Stern, medi ca l s tudents a t the Uni vers i ty of Ari zona , who s erved on a focus group to
provi de va l ua bl e i ns i ght for thi s text from a medi ca l s tudent pers pecti ve.


ABOUT THE AUTHORS
Ma rc E. Ti s chl er recei ved a n undergra dua te degree i n bi ol ogy from Bos ton Uni vers i ty, a ma s ter degree i n chemi s try from the Uni vers i ty of South
Ca rol i na , a nd hi s doctora te degree i n bi ochemi s try from the Uni vers i ty of Penns yl va ni a . After s ervi ng i n a pos tdoctora l pos i ti on i n phys i ol ogy
a t Ha rva rd Medi ca l School , he joi ned the fa cul ty a t the Uni vers i ty of Ari zona i n 1979 where he i s currentl y a profes s or of bi ochemi s try a nd
mol ecul a r bi ophys i cs hol di ng joi nt a ppoi ntments i n phys i ol ogy a nd i n i nterna l medi ci ne. Ha vi ng s erved a s coordi na tor of the medi ca l
bi ochemi s try cours e for a deca de, he wa s recrui ted to pl a y a ma jor rol e i n the devel opment of the revi s ed medi ca l curri cul um a t the Uni vers i ty
of Ari zona , whi ch debuted i n 2006 a nd offers a n i ntegra ted, orga n-ba s ed a pproa ch a ki n to the s econd ha l f of thi s textbook. In tha t new

curri cul um, he des i gned a nd s erves a s di rector of the medi ca l bl ock enti tl ed Di ges ti on, Meta bol i s m, a nd Hormones . He ha s ta ught more tha n
3000 medi ca l s tudents duri ng hi s tenure i n Ari zona .
Lee W. Ja ns on recei ved a BS i n Bi ochemi s try/mi nor i n La ti n from the Uni vers i ty of Roches ter fol l owed by a PhD i n bi ol ogi ca l
s ci ences /bi ochemi s try from Ca rnegi e Mel l on Uni vers i ty. After a pos tdoctora l fel l ows hi p a t NASA-Johns on Spa ce Center doi ng res ea rch on
i mmunol ogi ca l a cti va ti on i n mi crogra vi ty, he entered medi ca l s chool a t the Uni vers i ty of Texa s Southwes tern Medi ca l Center a t Da l l a s ,
conti nui ng wi th a fa mi l y pra cti ce res i dency i n both Da l l a s a nd Sa n Antoni o. He entered the a cti ve duty Ai r Force a nd s erved a s a fa mi l y
phys i ci a n a nd a fl i ght s urgeon, i ncl udi ng tours of Korea , Ira q, a nd Afgha ni s ta n. After mi l i ta ry s ervi ce, he perma nentl y moved to Edi nburgh,
Scotl a nd i n 2007, where he pra cti ces i n the Na ti ona l Hea l th Servi ce a s a n emergency room doctor a nd a genera l phys i ci a n i n the Uni ted
Ki ngdom wi th occa s i ona l work i n Aus tra l i a a nd other pa rts of the worl d. In hi s free ti me, he wri tes a nd does res ea rch. Pa s t book publ i ca ti ons
i ncl ude Brew Chem 101: The Basics of Home-brewing Chemistry (Storey Publ i s hi ng).


SECTION I
THE BASIC MOLECULES OF LIFE


CHAPTER 1
AMINO ACIDS AND PROTEINS
Ami no Aci ds —Structure a nd Functi ona l Groups
Ba s i c Protei n Structure
Ca tegori es of Protei ns
Revi ew Ques ti ons

OVERVIEW
Ami no a ci ds a re the ba s i c bui l di ng bl ocks of protei ns a nd s erve a s bi ol ogi ca l mol ecul es i n thei r own ri ght wi th a va ri ety of functi ons . Ami no
a ci ds a re often ca tegori zed a s es s enti a l or non-es s enti a l , dependi ng on the a bi l i ty of the body to ma nufa cture ea ch a mi no a ci d vers us
requi rement for i nges ti on i n the di et. Al though s evera l hundred a mi no a ci ds exi s t, 20 pl a y the predomi na nt rol e i n the huma n body. Ea ch
a mi no a ci d ha s a cha ra cteri s ti c R-group tha t determi nes i ts chemi ca l na ture a nd, therefore, how i t wi l l i ntera ct wi th other a mi no a ci ds , other
mol ecul es , a nd wi th i ts envi ronment.
Ami no a ci ds l i nk together vi a pepti de bonds to form pepti des a nd protei ns . Thes e pepti des a nd protei ns fol d i nto thei r fi na l threedi mens i ona l s ha pe a s the res ul t of hydrophobi c, hydrophi l i c, hydrogen bondi ng, a nd i oni c bondi ng forces (a mong others ) tha t res ul t from the

a mi no a ci ds i n the pepti de cha i n, i ncl udi ng the cha ra cteri s ti cs of thei r R-groups . Protei ns ma y be ca tegori zed a s enzymes , s tructura l protei ns ,
motor protei ns , a nd tra ns port/cha nnel protei ns . The s peci fi c rol es of a mi no a ci ds a nd protei ns i n the s ynthes i s of other mol ecul es a nd i n the
functi ons of orga n s ys tems a nd the huma n bodi es wi l l be expl ored i n deta i l i n s ubs equent cha pters .

AMINO ACIDS—STRUCTURE AND FUNCTIONAL GROUPS
ESSENTIAL AND NON-ESSENTIAL
Amino acids a re the ba s i c bui l di ng bl ocks of protei ns . Twenty a mi no a ci ds ma ke up protei ns i n l i vi ng orga ni s ms ; s evera l hundred more a mi no
a ci ds perform s peci a l i zed functi ons i n huma n a nd non-huma n bi ol ogy. Ami no a ci ds a re often des cri bed a s
Essential (mus t be obta i ned di rectl y from food)
Non-essential (the huma n body i s a bl e to produce them on i ts own).
There i s s ome deba te a bout the exa ct defi ni ti ons of thes e terms , but 8–10 a mi no a ci ds a re us ua l l y deemed es s enti a l a nd 10–12 a re nones s enti a l (s ee Ta bl e 1-1).


TABLE 1-1. Ami no Aci ds —R-Group Cl a s s i fi ca ti ons
Succota s h, a combi na ti on of corn a nd l i ma bea ns , wa s us ed by Na ti ve Ameri ca n hunters a nd wa rri ors . Li ght i n wei ght, ea s y to ca rry, a nd
s i mpl e to prepa re, s uccota s h conta i ns a l l the es s enti a l requi red a mi no a ci ds needed by huma ns a nd kept thes e tra vel ers wel l nouri s hed
a nd hea l thy duri ng l ong tri ps a wa y from thei r s ettl ements .

BASIC STRUCTURE
Every a mi no a ci d ha s four components l i nked together wi th a centra l ca rbon a tom (Fi gure 1-1):
1. Ami no group
2. Ca rboxyl i c a ci d group
3. Hydrogen a tom
4. R-group, whi ch va ri es wi th ea ch a mi no a ci d


Figure 1-1. Basic Structure of an Amino Acid. A central alpha (α) carbon is bonded to an amino group (NH 2 ), a carboxyl group (COOH), and an R group.
[Reproduced wi th permi s s i on from Na i k P: Bi ochemi s try, 3rd edi ti on, Ja ypee Brothers Medi ca l Publ i s hers (P) Ltd., 2009.]
CHARACTERISTICS OF R-GROUPS
As a mi no a ci ds a re i denti ca l except for thei r R-group, four R-group cha ra cteri s ti cs cl a s s i fy the a mi no a ci ds (s ee a l s o Ta bl e 1-1).

1. Hydrophobic (Water Hating) R-groups: Thes e a mi no a ci ds prefer to be i ns i de a fol ded protei n or covered by a nother pa rt of a protei n or a l i pi d
membra ne (Cha pter 8) where they a re hi dden from the externa l wa ter envi ronment.
2. Hydrophilic (Water Loving) R-groups: Wi th pa rti a l cha rges from the hydroxyl (OH −) or a mi no (NH 3 +) pa rts of thes e R-groups , thes e a mi no a ci ds
prefer to be a t or nea r the s urfa ce of a protei n where they i ntera ct wi th s urroundi ng wa ter mol ecul es . An excepti on woul d be the s urfa ce
porti on of a membra ne protei n tha t i ntera cts wi th the hydrophobi c regi on of the phos phol i pi d bi l a yer (Cha pter 8). Hydrophi l i c R-groups a re
often i mporta nt a t the a cti ve s i te of a n enzyme (Cha pter 5).
3. Charged R-groups: Ei ther pos i ti vel y or nega ti vel y cha rged, thes e a mi no a ci ds prefer to be a t the s urfa ce of a fol ded protei n or i n conta ct wi th
other cha rged a toms /mol ecul es .
4. Special R-groups: There a re four a mi no a ci ds wi th s peci a l qua l i ty R-groups .
• Prol i ne ha s a gl uta ma te R-group tha t ha s bonded onto i ts el f (s ee Fi gure 1-2A) formi ng a n “i mi no” a ci d. Prol i ne i s often found a t s ha rp
turns of fol ded protei ns (Fi gure 1-2B).

Figure 1-2. A–B. Proline. A. Prol i ne forms from the a mi no a ci d gl uta ma te when the a mi no group ni trogen (bl ue) crea tes a bond wi th ca rbon 2 on
the R-group (red), ma ki ng a n a mi no a ci d tha t i s “fol ded” onto i ts el f. The ca rbon a toms a re i ndi vi dua l l y numbered to a l l ow the rea der to fol l ow
the proces s tha t ta kes three s teps (i ndi ca ted by a rrows ). B. Prol i ne’s s peci a l s tructure a l l ows the forma ti on of a “ha i rpi n” β-turn vi a forma ti on
of a n i mi no bond. The a mi no group from prol i ne i s s ha ded i n bl ue. [Ada pted wi th permi s s i on from Na i k P: Bi ochemi s try, 3rd edi ti on, Ja ypee
Brothers Medi ca l Publ i s hers (P) Ltd., 2009.]
• Cys tei ne ha s a s ul fhydryl group tha t ca n bond wi th a nother cys tei ne s ul fhydryl group to form a cys ti ne “di s ul fi de” bond (Fi gure 1-3). Thi s
bond ca n be ei ther wi thi n one protei n or between two di fferent protei ns a nd i s i mporta nt i n ma ki ng s trong s tructures s uch a s the protei n
kera ti n found i n fi ngerna i l s .


Figure 1-3. Formation of Cystine Disulfide Bond. The s ul fhydryl groups (SH) from two cys tei ne a mi no a ci d res i dues from di fferent pa rts of a s i ngl e
or two s epa ra te a mi no a ci d s equences ma y l os e one hydrogen a tom ea ch to become a cys ti ne res i due by the forma ti on of a di s ul fi de bond (S
—S). [Ada pted wi th permi s s i on from Na i k P: Bi ochemi s try, 3rd edi ti on, Ja ypee Brothers Medi ca l Publ i s hers (P) Ltd., 2009.]
• Methi oni ne ha s a s ul fur a tom conta i ned wi thi n i ts R-group. Al though i t does not ma ke di s ul fi de bonds , thi s s ul fur i s s een a t the s i te of
s ome enzyme rea cti ons or a t s peci a l a rea s of protei n s tructure.
• Hi s ti di ne ha s a uni que i mi da zol e ri ng conta i ni ng two ni trogen a toms , whi ch ca n be uncha rged or pos i ti vel y cha rged. Thi s uni que
cha ra cteri s ti c ma kes the hi s ti di ne R-group i mporta nt i n enzyme rea cti ons tha t ma ke or brea k bonds .
Hair and Cystine Double Bonding: Ha i r, whi ch i s compos ed of l i nea r protei n s equences , i s curl y or s tra i ght dependi ng on the number of cys ti ne

di s ul fi de bonds . The number a nd l oca ti on of cys tei ne res i dues a nd a cces s ory protei ns s peci fi c for ea ch pers on a ffect the number of
di s ul fi de bonds res ul ti ng i n thi s very i ndi vi dua l i zed cha ra cteri s ti c. Chemi ca l s tha t promote thes e di s ul fi de bonds a re us ed for “perms ” a nd,
a l terna ti vel y, chemi ca l s tha t brea k thes e bonds a re us ed i n ha i r s tra i ghteni ng trea tments .

BASIC PROTEIN STRUCTURE
Severa l fa ctors a ffect ba s i c protei n s tructure, i ncl udi ng the fol l owi ng:
Amino Acid Composition: Whether the R-group of ea ch a mi no a ci d wa nts to be a wa y from, nea r, or i n conta ct wi th wa ter a t the s urfa ce of the
fol ded protei n.
Special Amino Acids: Prol i ne, cys tei ne, a nd/or methi oni ne exert effects on protei n fol di ng due to res ul ti ng bends a nd di s ul fi de bonds .
Functional Sites: Structura l protei ns or protei ns tha t ca ta l yze a rea cti on (i .e., enzymes ; Cha pter 5) us ua l l y conta i n s peci fi c a mi no a ci ds tha t a re
i mporta nt for tha t protei n’s pa rti cul a r functi on. The R-groups a t thes e s i tes wi l l a ffect the protei n’s fi na l fol ded s ha pe.
Final Modifications: Mos t protei ns a re i ni ti a l l y ma de wi th extra a mi no a ci ds a t thei r begi nni ng a nd/or end. Thes e extra a mi no a ci ds ma y be
modi fi ed or removed duri ng the ma tura ti on of the protei n, res ul ti ng i n cha nges to the fi na l s tructure.
Final Destination: Whether the protei n wi l l end up i n a n a queous s ol uti on or i n a membra ne wi l l a l s o cha nge the fol di ng, a s protei ns tha t go
to membra nes wi l l ul ti ma tel y wa nt thei r hydro-phobi c, “wa ter ha ti ng” R-groups on the outs i de i n conta ct wi th the hydrophobi c membra ne
(s ee bel ow, Cha pter 8).
LEVELS OF PROTEIN STRUCTURE
When des cri bi ng protei n s tructure, we us e the fol l owi ng terms : pri ma ry (1°), s econda ry (2°), terti a ry (3°), a nd/or qua terna ry (4°) s tructure.
Primary (1°) Structure: The pa rti cul a r s equence of a mi no a ci ds i n a protei n (a l s o ca l l ed a polypeptide) i s termed a s primary structure. The a mi no
a ci ds wi thi n a pol ypepti de a re termed residues a nd a re l i nked vi a peptide bonds (Fi gure 1-4A), formed when the ca rboxyl i c a ci d group of one
a mi no a ci d i ntera cts wi th the a mi no group of a s econd a mi no a ci d. The combi na ti on produces the pepti de bond a nd one mol ecul e of wa ter.
Repea ted pepti de bonds form a cha i n of pepti de bond l i nka ges wi th the ni trogen from the a mi no group, the centra l ca rbon from the a mi no
a ci d, a nd the ca rbon from the ca rboxyl i c a ci d formi ng the protei n “ba ckbone.” The pri ma ry s tructure i s often s hown a s “bea ds on a s tri ng”
wi th ea ch bea d repres enti ng a n a mi no a ci d res i due (Fi gure 1-4B).

Figure 1-4. A. Formation of a Peptide Bond. A pepti de bond i s formed between the ca rboxyl i c a ci d (COOH) group a nd the a mi no ni trogen (HHN)
group to form a new C—N bond. The proces s rel ea s es one mol ecul e of wa ter (OH a nd H a s s hown i n pi nk ci rcl e). By conventi on a protei n i s
a l wa ys dra wn s ta rti ng wi th the N-termi nus on the l eft. [Reproduced wi th permi s s i on from Ba rrett KE, et a l .: Ga nong’s Revi ew of Medi ca l
Phys i ol ogy, 23rd edi ti on, McGra w-Hi l l , 2010.] B. Primary (1°) Structure. The pri ma ry s tructure of a protei n i s the cha i n of a mi no a ci ds from the Ntermi na l (NH 2 group of a mi no a ci d 1) to i ts C-termi na l end (COOH group of the fi na l a mi no a ci d). Indi vi dua l a mi no a ci ds a re denoted a s green
“bea ds ” a nd bonds a re red “s tri ngs ” i n thi s s tyl i zed repres enta ti on. Protei ns va ry grea tl y i n l ength from a few a mi no a ci ds to s evera l hundred.

[Reproduced wi th permi s s i on from Na i k P: Bi ochemi s try, 3rd edi ti on, Ja ypee Brothers Medi ca l Publ i s hers (P) Ltd., 2009.]
Secondary (2°) Structure: From the l i nea r cha i n of a mi no a ci ds , the C—N a nd C—C bonds rota te a round the centra l ca rbon a tom (s ee Fi gure 1-1).
Thi s rota ti on forms secondary structures (Fi gure 1-5A–C) ca l l ed a n α-helix, β-strand, or β-turn (s ee a l s o Fi gure 1-2B a bove) dependi ng on the


hydrophi l i c a nd hydrophobi c cha rge a nd s i ze i nfl uences of the R-groups a s wel l a s hydrogen a nd i oni c bondi ng. Pa rts of the pepti de tha t do
not form conventi ona l s econda ry s tructures a re referred to a s “ra ndom coi l .”

Figure 1-5. A–C. Secondary (2°) Structure. A. The α-hel i x s tructure i s s ta bi l i zed by hydrogen bonds (bl ue dotted l i ne) between the N—H of one
a mi no a ci d a nd the
of a nother a mi no a ci d. The hydrophobi c a nd hydrophi l i c na ture of the R-groups from ea ch a mi no a ci d i n the hel i x
a l s o pl a ys a pa rt i n forma ti on of the α-hel i x. B. The β-s tra nds form when the one s equence of s ucces s i ve a mi no a ci ds form hydrogen bonds
between the N—H a nd the C═O of a nother group of s ucces s i ve a mi no a ci ds . R-groups of thes e a mi no a ci ds a l s o i nfl uence the forma ti on of βs tra nds by both cha rge a nd s teri c forces . β-Stra nds ca n be ei ther pa ra l l el (l eft) or a nti pa ra l l el (ri ght) a s noted by the a rrows . C. A β-turn forms
a t the juncture between two a nti pa ra l l el β-s tra nds a nd us ua l l y i nvol ves a mi no a ci ds wi th s ma l l R-groups , i ncl udi ng gl yci ne, a l a ni ne, a nd
va l i ne. β-turns ca n a l s o form vi a prol i ne’s uni que s tructure (Fi gure 1-2B). [Ada pted wi th permi s s i on from Na i k P: Bi ochemi s try, 3rd edi ti on,
Ja ypee Brothers Medi ca l Publ i s hers (P) Ltd., 2009.]
Tertiary (3°) Structure: Seconda ry s tructure a nd the rema i ni ng a mi no a ci d s equences conti nue to fol d a nd i ntera ct wi th other pa rts of the a mi no
a ci d s equence to form terti a ry (3°) s tructure. Thes e proces s es a ga i n a re dri ven by hydrophobi c a nd hydrophi l i c forces of the i ndi vi dua l pa rts
of the s equence, a s wel l a s hydrogen bondi ng a nd i oni c bondi ng between cha rged a mi no a ci d R-groups . In pa rti cul a r, R-groups a nd the
pa rti a l pos i ti ve cha rge of the ni trogen a nd nega ti ve cha rge of oxygen (OH − a nd C═O−) mol ecul es often form hydrophi l i c a nd hydrophobi c
“s i des ” of the α-hel i x or β-s tra nd. As a res ul t, thes e s econda ry s tructures wi l l pos i ti on thems el ves wi th ea ch other a nd wi th other s i mi l a r
a rea s of the fol ded protei n to keep thei r hydrophobi c a rea s a wa y from a nd thei r hydrophi l i c a rea s expos ed to the externa l wa ter
envi ronment. Exa mpl es a re s hown i n Fi gure 1-6. Addi ti ona l l y, terti a ry s tructure s ta rts to devel op a t a cti ve s i tes of protei ns where cri ti ca l
a cti ons a nd i ntera cti ons wi l l ta ke pl a ce. Thes e a cti ve s i tes wi l l be di s cus s ed i n s ubs equent cha pters .

Figure 1-6. Examples of Tertiary (3°) Structure. Seconda ry s tructures , i ncl udi ng α-hel i ces , β-s heets , β-turns /bends , a nd l oop regi ons combi ne to
form terti a ry s tructure doma i ns . Severa l common forms of terti a ry s tructure ha ve been cha ra cteri zed a nd a re i l l us tra ted i n the fi gure.
[Reproduced wi th permi s s i on from Na i k P: Bi ochemi s try, 3rd edi ti on, Ja ypee Brothers Medi ca l Publ i s hers (P) Ltd., 2009.]
Globular vs. Fibrous Proteins: Protei ns a re often grouped i nto the broa d ca tegori es of “gl obul a r”—ha vi ng a n a pproxi ma tel y s pheri ca l threedi mens i ona l s ha pe—or “fi brous ”—bei ng l ong a nd fa i rl y s tra i ght overa l l . A va s t ma jori ty of protei ns a re gl obul a r, wi th fi brous protei ns often
pl a yi ng s tructura l or very s peci a l i zed functi ona l rol es . Exa mpl es of fi brous protei ns i ncl ude a cti n, col l a gen, a nd kera ti n, whi ch pl a y

s tructura l rol es i n mus cl e, connecti ve ti s s ue, a nd s ki n/na i l s .
Quaternary (4°) Structure: Al though ma ny protei ns a re ma de of onl y one pepti de cha i n (ca l l ed “monomers ” or “s ubuni ts ”), two or more fol ded
cha i ns ma y combi ne together to ma ke a fi na l a cti ve “ol i gomer” protei n. The s ubuni ts i n a mul ti meri c protei n ma y ha ve i denti ca l (homooligomer) or di fferent (hetero-oligomer) a mi no a ci d s equences a nd i ntera ct to opti mi ze hydrophobi c a nd hydrophi l i c a rea s a nd hydrogen/ i oni c
bondi ng. The combi na ti on of the mul ti pl e protei n s ubuni ts ma kes qua terna ry (4°) s tructure (Fi gure 1-7).

Figure 1-7. Quaternary (4°) Structure. Protei n monomers ma y joi n, hel d together by hydrogen bondi ng (s hown) a nd/or hydrophobi c–hydrophi l i c
i ntera cti ons , to ma ke ol i gomers . Identi ca l protei n s ubuni t monomers ma y joi n together to ma ke a homo-ol i gomer. Noni denti ca l protei n
s ubuni t monomers ma y joi n together to ma ke a hetero-ol i gomer. [Reproduced wi th permi s s i on from Na i k P: Bi ochemi s try, 3rd edi ti on, Ja ypee
Brothers Medi ca l Publ i s hers (P) Ltd., 2009.]
The proces s of protei n fol di ng i s not a trul y l i nea r one; a protei n never exi s ts a s a l ong a mi no a ci d s tri ng. Ins tea d, protei n fol di ng i s a
compl ex i ntera cti on of thes e proces s es a nd s econda ry a nd terti a ry s tructures a ctua l l y form s omewha t i n pa ra l l el . Ma ny more compl ex fa ctors
not di s cus s ed here a l s o occur to hel p i n determi ni ng the fi na l protei n conforma ti on. The proces s of ma ki ng a nd tra ffi cki ng a protei n wi l l be
expl ored more ful l y i n Cha pters 5 a nd 9.
Dystrophin and Muscular Dystrophy: Mus cul a r dys trophi es (i ncl udi ng Duchenne a nd Becker mus cul a r dys trophi es ) a re di s ea s es i n whi ch
s kel eta l mus cl e ra pi dl y brea ks down, res ul ti ng i n mus cl e wea knes s a nd wa s ti ng, decrea s ed motor s ki l l s , a nd, eventua l l y, the i na bi l i ty to
wa l k (us ua l l y by the a ge of 12 yea rs ). Of a pproxi ma tel y, 30 di fferent types of mus cul a r dys trophi es , the Duchenne a nd Becker forms s how X
chromos ome-l i nked i nheri ta nce a nd, therefore, a l mos t a l wa ys a ffect ma l es a t a ra te of a pproxi ma tel y one i n 3500 boys worl dwi de. Both a re
ca us ed by the a bs ence or muta ti on of the protei n dystrophin, whi ch provi des s trength for s kel eta l mus cl e cel l s by a nchori ng the i nterna l cel l
components to the extra cel l ul a r ma tri x.


Reproduced wi th permi s s i on from Ka ndel l E, et a l .: Pri nci pl es of Neuros ci ence, 4th edi ti on, McGra w-Hi l l , 2000.
The i ntera cti on of dys trophi n wi th s evera l other protei ns i nvol ved i n thi s s tructura l s upport network i s a pri me exa mpl e of protei n–
protei n i ntera cti ons i nvol vi ng the forces of thei r hydrophobi c a nd hydrophi l i c regi ons . More i mporta ntl y, the muta ti ons i n the dys trophi n
protei n a re bel i eved to s i gni fi ca ntl y a l ter one or more of thes e regi ons , res ul ti ng i n brea kdown of the a nchori ng compl ex a nd thus di s ea s e.

CATEGORIES OF PROTEINS
AMINO ACID AND PEPTIDE-DERIVED HORMONES AND NEUROTRANSMITTERS

Ami no a ci ds a nd the pepti des /protei ns tha t they form s erve s evera l cri ti ca l rol es i n huma n bi ochemi s try a nd l i fe. The ma jor rol e of a mi no
a ci ds i s to provi de the bui l di ng bl ocks for protei ns a nd a va s t ma jori ty of the body’s a mi no a ci ds a re i nvol ved i n thi s functi on. However, a mi no
a ci ds a re a l s o the ma jor precurs ors of s evera l bi ol ogi ca l l y i mporta nt mol ecul es , a s noted i n Ta bl e 1-2.

TABLE 1-2. Ami no Aci ds —Components of Va ri ous Bi ol ogi ca l Mol ecul es
Quaternary (4°) Structure: Qua terna ry (4°) s tructure i s exempl i fi ed i n ma ny other wa ys tha n thos e gi ven a bove, where two s econda ry s tructura l
el ements a re s i mpl y i n cl os e proxi mi ty to ea ch other. Ma ny fi brous protei ns expa nd on thi s concept, wi th two or more α-hel i ces wound
a round ea ch other for mos t of thei r a mi no a ci d s equence. Exa mpl es i ncl ude F-a cti n a nd the ta i l s ecti on of myos i n, kera ti n i n ha i r, a nd
i ntermedi a te fi l a ments , whi ch pl a y a n i mporta nt s tructura l rol e i ns i de a l l cel l s .

Reproduced wi th permi s s i on from Mes cher AL: Junquei ra ’s Ba s i c Hi s tol ogy Text a nd Atl a s , 12th edi ti on, McGra w-Hi l l , 2010
Collagen, a nother fi brous s tructura l protei n of s ki n a nd connecti ve ti s s ue, i s compos ed of three i ntertwi ned hel i ca l protei n s equences
(s ee the fi gure on ri ght), whi ch di ffer from the α-hel i ca l s tructure. Unl i ke a n α-hel i x where hydrogen bondi ng wi thi n the s a me protei n
s equence predomi na tes , col l a gen uti l i zes hydrogen bondi ng between the three hel i ca l protei n cha i ns . Col l a gen opti mi zes thi s very uni que
s tructure by ha vi ng the s ma l l a mi no a ci d gl yci ne a s every thi rd a mi no a ci d to a l l ow the three hel i ces to fi t very cl os e together (s ee the fi gure
bel ow). In a ddi ti on, col l a gen ha s a n a bunda nce of prol i ne res i dues to promote the hel i ca l protei n s tructure a nd a s peci a l form of prol i ne
(hydroxyprol i ne) wi th a n extra hydroxyl (OH –) to form the i nterprotei n hydrogen bonds wi th the gl yci ne NH groups . Hydroxyl ys i ne res i dues
hel p to s ta bi l i ze the s tructure a s wel l .


Ada pted (l eft) a nd reproduced (ri ght) wi th permi s s i on from Na i k P: Bi ochemi s try, 3rd edi ti on, Ja ypee Brothers Medi ca l Publ i s hers (P) Ltd.,
2009.
Osteogenesis imperfecta (OI) i s a geneti c di s ea s e tha t a ffects col l a gen-conta i ni ng ti s s ues s uch a s bone, s ki n, joi nts , eyes , ea rs , a nd teeth
beca us e of poi nt muta ti ons tha t des ta bi l i ze or a l ter col l a gen’s i mporta nt tri pl e hel i x s tructure. Pa ti ents wi th OI often di s pl a y frequent
fra ctures a nd ea s y brui s i ng (s ometi mes mi s ta ken for chi l d a bus e); wea k joi nts ; a bl ui s h col or to the norma l l y whi te pa rt of thei r eyes ;
hea ri ng l os s due pa rtl y to a bnorma l i ti es of the i nner ea r bones ; a nd poorl y s ha ped, s ma l l , bl ue-yel l ow teeth.
As a res ul t, ei ther the exces s or defi ci ency of a mi no a ci ds ca n l ea d di rectl y to di s ea s e tha t ma y res ul t i n centra l nervous s ys tem defects ,
di eta ry a nd meta bol i s m probl ems , l i ver a nd ki dney fa i l ure, s ki n a nd eye l es i ons , a nd even dea th.
ENZYMES
Enzymes a re s peci a l i zed protei ns tha t a ccel era te a chemi ca l rea cti on by s ervi ng a s a bi ol ogi ca l ca ta l ys t. By ca ta l yzi ng thes e rea cti ons ,

enzymes ca us e them to ta ke pl a ce one mi l l i on or more ti mes fa s ter tha n i n thei r a bs ence. Enzymes a re us ua l l y i denti fi ed by the endi ng of
“a s e” to thei r na me (e.g., hexoki na s e, the fi rs t enzyme i n the brea kdown of gl ucos e). There a re excepti ons for enzymes tha t were di s covered
before thi s na mi ng s cheme wa s a dopted (e.g., tryps i n, peps i n, a nd thrombi n). Enzyme rea cti ons wi l l be di s cus s ed i n grea ter deta i l i n Cha pter
5.
STRUCTURAL PROTEINS
Protei ns a l s o s erve a n i mporta nt rol e a s s tructura l el ements of cel l s a nd ti s s ues . The bes t exa mpl es of thes e protei ns a re a cti n a nd tubul i n,
whi ch form a cti n fi l a ments a nd mi crotubul es , res pecti vel y (Fi gure 1-8A-B). In s kel eta l mus cl e, a cti n fi l a ments provi de the “s ca ffol di ng” a ga i ns t
whi ch the motor protei n myos i n ca n genera te force to produce mus cl e contra cti on. In s mooth mus cl e a nd non-mus cl e (e.g., s ki n a nd i mmune
s ys tem), a cti n fi l a ments crea te the mecha ni ca l s tructure of the cel l a nd a re di rectl y a s s oci a ted wi th l i nka ges to s urroundi ng cel l s a l l owi ng
i ntercel l ul a r s i gna l i ng. The a cti n fi l a ments a l s o provi de tra cks on whi ch s peci a l i zed myos i n mol ecul es move ves i cl es a nd orga nel l es (s ee
Cha pter 12). Fi na l l y, a cti n fi l a ments a re i nti ma tel y i nvol ved i n cel l moti l i ty, a wi de a rra y of cel l ul a r movements s uch a s wound hea l i ng (the
movement of s ki n cel l s i nto cuts ), the i mmune res pons e (the proces s of whi te bl ood cel l s conta cti ng a nd recogni zi ng ea ch other i n the hi ghl y
s el ecti ve proces s of i mmune rea cti ons ), a nd cytoki nes i s (the di vi s i on of one cel l i nto two duri ng mi tos i s ).

Figure 1-8. A–B. A. Actin and B. Tubulin in Monomer and Filamentous Forms. [Ada pted wi th permi s s i on from Ba rrett KE, et a l .: Ga nong’s Revi ew of
Medi ca l Phys i ol ogy, 23rd edi ti on, McGra w-Hi l l , 2010.]
The s tructura l protei n tubul i n crea tes mi crotubul e tra cks for the movement by two mol ecul a r motor protei ns , dynei n a nd ki nes i n, of
ves i cl es , gra nul es , orga nel l es , a nd chromos omes . Mi crotubul es a re a l s o the s tructura l component i n fl a gel l a a nd ci l i a i nvol ved i n functi ons
s uch a s s perm moti l i ty, the movement of the egg down the Fa l l opi a n tubes , a nd the expul s i on of di rt a nd mucus out of the l ungs a nd tra chea .
Nonmoti l e ci l i a a re a l s o i mporta nt i n rod cel l s i n the eye a nd neurons i nvol ved i n ol fa cti on (s mel l ). Mi crotubul es a l s o s erve a mecha ni ca l –
s tructura l rol e i n the cel l s i mi l a r to a cti n mi crofi l a ments a nd a re res pons i bl e for the movement a nd s epa ra ti on of chromos omes duri ng
mi tos i s (s ee Cha pter 12).
MOTOR PROTEINS


“Motor” protei ns tra ns port mol ecul es i ns i de a cel l , provi de movement of certa i n pa rts of i ndi vi dua l cel l s i nvol ved i n s peci a l i zed functi ons
(e.g., i mmune res pons es a nd wound hea l i ng), genera te l a rger s ca l e movements of fl ui ds a nd s emi s ol i ds s uch a s the ci rcul a ti on of bl ood a nd
movement of food through the di ges ti ve tra ct, a nd fi na l l y provi de movement of the huma n body through thei r rol es i n s kel eta l mus cl es .
Myos i n i s a protei n wi th a hydrophobi c ta i l ; a hea d group, whi ch ca n a tta ch a nd deta ch from a cti n fi l a ments ; a nd a “hi nge” s ecti on, whi ch
moves the hea d group ba ck a nd forth res ul ti ng i n movement. Two ma jor types of myos i n exi s t. Myos i n I i s compos ed of one mol ecul e wi th a n

a ddi ti ona l a rea on i ts s hort ta i l tha t ca n bi nd to other protei ns a nd membra nes . Myos i n II (s evera l s ubtypes exi s t) i s compos ed of a l ong ta i l
tha t bi nds vi a hydrophobi c i ntera cti ons to other myos i n II mol ecul es , res ul ti ng i n a compos i te mol ecul e tha t ca n s horten s kel eta l mus cl es by
i ts i ntera cti on wi th a cti n fi l a ments i n thos e mus cl es . Ki nes i n a nd dynei n a re very much l i ke myos i n I i n form a nd functi on (s ee Cha pter 12).
Microtubules, Cilia, and Flagella—Roles in Disease Processes: Al though us ua l l y ra re, defects i n ci l i a /fl a gel l a , known a s ci l i opa thi es , l ea d to
s evera l di s ea s es /s yndromes i ncl udi ng the fol l owi ng:
Kartagener Syndrome/Primary Ciliary Dyskinesia—defecti ve ci l i a i n the res pi ra tory tra ct, Eus ta chi a n tube, a nd Fa l l opi a n tubes l ea di ng to chroni c
l ung i nfecti ons , ea r i nfecti ons a nd hea ri ng l os s , a nd i nferti l i ty. Pos s i bl e a s s oci a ti on wi th “s i tus i nvers us ,” a condi ti on i n whi ch ma jor
i nterna l orga ns a re “fl i pped” l eft to ri ght.
Senior–Loken Syndrome/Nephronophthisis—eye di s ea s e a nd forma ti on of cys ts i n the ki dneys l ea di ng to rena l fa i l ure.
Bardet–Biedl Syndrome—dys functi on of ci l i a throughout the body l ea di ng to obes i ty due to i na bi l i ty to s ens e s a ti a ti on, l os s of eye
pi gment/vi s ua l l os s a nd/or bl i ndnes s , extra di gi ts a nd/or webbi ng of fi ngers a nd toes , menta l a nd growth reta rda ti on a nd beha vi ora l
/s oci a l probl ems , s ma l l a nd/or mi s s ha ped geni ta l i a (ma l e a nd fema l e), enl a rged a nd da ma ged hea rt mus cl e, a nd ki dney fa i l ure.
Alstrom Syndrome—chi l dhood obes i ty, brea kdown of the reti na l ea di ng to bl i ndnes s , hea ri ng l os s , a nd type 2 di a betes .
Meckel–Gruber Syndrome—forma ti on of cys ts i n ki dneys a nd bra i n l ea di ng to rena l fa i l ure a nd neurol ogi ca l defi ci ts , extra di gi ts a nd
bowi ng/s horteni ng of the l i mbs .
Increased Ectopic (Tubal) Pregnancies/Male Infertility—defi ci ent ci l i a i n Fa l l opi a n tubes or defi ci ent fl a gel l a / s perm ta i l moti l i ty.
Autosomal Recessive Polycystic Kidney Disease—much ra rer tha n the a utos oma l domi na nt form, dys functi on of ba s a l bodi es a nd ci l i a i n rena l
cel l s l ea ds to a l tera ti ons of the l ungs a nd ki dneys l ea di ng to a va ri ety of s econda ry medi ca l condi ti ons a nd often dea th.
Parkinson’s and Alzheimer’s diseases—Al though work i s s ti l l ongoi ng, res ea rchers now feel tha t s ome forms of Pa rki ns on’s a nd Al zhei mer’s
di s ea s es ma y res ul t, i n pa rt, from da ma ge to mi crotubul es a nd a s s oci a ted protei ns . Trea tments a i med a t s ta bi l i zi ng mi crotubul es ma y
hel p ma ny s ufferers of thes e ma l a di es .
TRANSPORT/CHANNEL PROTEINS
Another group of protei ns fol d i nto a terti a ry or qua terna ry s tructure tha t crea tes cha nnel s for the movement of mol ecul es i nto a nd out of the
nucl eus , va ri ous cel l orga nel l es , a nd from cel l s to thei r outs i de envi ronment s uch a s the bl ood s trea m. The hydrophobi c a nd hydrophi l i c
na ture of the a mi no a ci ds tha t ma ke up thes e cha nnel protei ns a l l ows a n exteri or of the protei n tha t ca n exi s t i ns i de the extremel y
hydrophobi c envi ronment of a membra ne bi l a yer a nd a hydrophi l i c i nteri or tha t ca n a l l ow cha rged mol ecul es to move through the membra ne
(Cha pter 8). Cha nnel s a re es s enti a l for the tra ns porta ti on of nutri ents i nto a nd out of cel l s a s wel l a s for nerve s i gna l s a nd the s el ecti ve
fi l tra ti on of mol ecul es i n the ki dneys . Thes e s peci a l i zed functi ons of cha nnel s wi l l be di s cus s ed i n deta i l i n Cha pter 8 a nd Secti on III.

REVIEW QUESTIONS

1. Wha t i s the mea ni ng a nd s i gni fi ca nce of es s enti a l a nd non-es s enti a l a mi no a ci ds ?
2. Wha t i s the s i gni fi ca nce of ea ch a mi no a ci d R-group (hydrophobi c, hydrophi l i c, a nd cha rged)?
3. Wha t a re the four ma jor types of s tructura l el ements of protei ns a nd how a re they defi ned?
4. Wha t i s a n enzyme a nd how do the terms ca ta l ys t a nd a cti ve s i te rel a te to enzymes ?
5. Wha t i s the ba s i c s tructure of a mi no a ci ds ?
6. How do the el ements pepti de bond, pepti des , α-hel i x, β-s tra nd, β-turn, ha i rpi n turn, a nd di s ul fi de bond rel a te to the s tructure of protei ns ?
7. How does a n a mi no a ci d s equence fol d?
8. Wha t a re the rol es of R-groups a nd pri ma ry to qua terna ry s tructure i n the fi na l conforma ti on of protei ns ?
9. Wha t a re the di fferent ca tegori es of protei ns a nd how a re they defi ned?


CHAPTER 2
CARBOHYDRATES
Ba s i c Ca rbohydra te Structure a nd Functi on
Monos a ccha ri des a nd Di s a ccha ri des
Gl ycogen a nd Sta rches
Gl ycoprotei ns
Gl ycos a mi nogl yca ns
Revi ew Ques ti ons

OVERVIEW
Ca rbohydra tes a re va s tl y i mporta nt i n huma n bi ol ogy, i ncl udi ng rol es a s a ma jor energy s ource, s tructura l mol ecul es when combi ned wi th
other ca rbohydra tes , protei ns , a nd other mol ecul es , a nd bi ndi ng a nd s i gna l i ng between mol ecul es a nd cel l s . As a res ul t of a l l thes e
i mporta nt functi ons , ca rbohydra te bi ochemi s try i s i nvol ved i n a l a rge number of di s ea s e s ta tes . Al though mul ti pl e ca rbohydra tes exi s t, onl y a
few s uga r mol ecul es a nd pol ys a ccha ri des a re i mporta nt to huma n phys i ol ogy (e.g. onl y ei ght di fferent ca rbohydra tes a re found a s
cons ti tuents of gl ycoprotei ns a nd gl ycol i pi ds ). However, a number of a ddi ti ona l mol ecul es crea ted by l i nka ges of ca rbohydra tes to protei ns
pl a y va ri ous rol es i n cel l –cel l i ntera cti ons a nd bi ol ogi ca l s tructures .

BASIC CARBOHYDRATE STRUCTURE AND FUNCTION
Carbohydrates, whos e na mes end i n “-ose,” ha ve a formul a of (CH 2 O) x where x i s a number from three to s even (gi vi ng the na mes of triose,

tetros e, pentose, hexose, a nd heptose). Al l ca rbohydra tes conta i n a ketone or a n a l dehyde group, a s wel l a s one or more hydroxyl groups (Fi gure
2-1A–B; Appendi x III). The oxygen a toms of the ketone a nd a l dehyde groups ha ve s i mi l a r rea cti ve qua l i ti es to tha t of the ca rboxyl i c a ci d group
s een i n a mi no a ci ds a nd a re the s i tes of chemi ca l rea cti ons wi thi n the ca rbohydra te mol ecul e, a s wel l a s wi th other ca rbohydra te, protei n, or
l i pi d mol ecul es . Often, the ketone or a l dehyde rea cts wi th a hydroxyl group from the s a me s uga r mol ecul e to form a ca rbohydra te ri ng
s tructure a s s hown.

Figure 2-1. A–B. Basic Carbohydrate Structures. A. The rea cti ve ketone group of ca rbon 2 (green ca rbon group) from the hexos e fructos e rea cts wi th
the hydroxyl group of ca rbon 5 to form a new bond a nd a fi ve-s i ded (pentos e) ri ng s tructure. Al l ca rbon a toms a re numbered for cl a ri ty. Thi s
rea cti on i s ful l y revers i bl e a s i ndi ca ted by the bi di recti ona l a rrows . As a res ul t, the l i nea r a nd ri ng s tructures a re cons ta ntl y cha ngi ng i n
s ol uti on. B. The rea cti ve a l dehyde group of ca rbon 1 (green ca rbon group) from the hexos e gl ucos e rea cts wi th the hydroxyl group of ca rbon 5 to
form a new bond a nd a s i x-s i ded (hexos e) ri ng s tructure. Al l ca rbon a toms a re numbered for cl a ri ty. Thi s rea cti on i s ful l y revers i bl e a s
i ndi ca ted by the bi di recti ona l a rrows . As a res ul t, the l i nea r a nd ri ng s tructures a re cons ta ntl y cha ngi ng i n s ol uti on. [Ada pted wi th permi s s i on
from Na i k P: Bi ochemi s try, 3rd edi ti on, Ja ypee Brothers Medi ca l Publ i s hers (P) Ltd., 2009.]
Ca rbohydra tes pl a y a ma jor rol e i n huma ns a s energy s ources a nd s tora ge, a nd thei r rol e i n di et a nd nutri ti on, a l though s ometi mes
controvers i a l , i s a l wa ys one of s upreme i mporta nce. However, ca rbohydra tes pl a y other rol es a s noted i n Ta bl e 2-1.