CHAPTER-I

INTRODUCTION TO BIOCHEMISTRY

CELL AND ITS ORGANIZATION

The cell is the basic structural and functional unit of all known living organisms. It is the
smallest unit of life that is classified as a living thing, and is often called the building block of
life. Organisms can be classified as unicellular (consisting of a single cell; including most
bacteria) or multicellular (including plants and animals). Humans contain about 10 trillion (1013)
cells. Most plant and animal cells are between 1 and 100 m and therefore are visible only under
the microscope. The cell was discovered by Robert Hooke in 1665. The cell theory, first
developed in 1839 by Matthias Jakob Schleiden and Theodor Schwann, states that all organisms
are composed of one or more cells, that all cells come from preexisting cells, that vital functions
of an organism occur within cells, and that all cells contain the hereditary information necessary
for regulating cell functions and for transmitting information to the next generation of cells.

TYPES OF CELLS

There are two types of cells: eukaryotic and prokaryotic The prokaryote cell is simpler, and
therefore smaller, than a eukaryote cell, lacking a nucleus and most of the other organelles of
eukaryotes.

SUBCELLULAR COMPONENTS

All cells, whether prokaryotic or eukaryotic, have a membrane that envelops the cell, separates
its interior from its environment, regulates what moves in and out (selectively permeable), and
maintains the electric potential of the cell. Inside the membrane, a salty cytoplasm takes up most
of the cell volume. All cells possess DNA, the hereditary material of genes, and RNA, containing
the information necessary to build various proteins such as enzymes, the cell's primary
machinery. There are also other kinds of biomolecules in cells. This article lists these primary
components of the cell, then briefly describe their function.

MEMBRANE

The cytoplasm of a cell is surrounded by a cell membrane or plasma membrane. The plasma
membrane in plants and prokaryotes is usually covered by a cell wall. This membrane serves to
separate and protect a cell from its surrounding environment and is made mostly from a double
layer of lipids (hydrophobic fat-like molecules) and hydrophilic phosphorus molecules. Hence,
the layer is called a phospholipid bilayer. It may also be called a fluid mosaic membrane.
Embedded within this membrane is a variety of protein molecules that act as channels and pumps
that move different molecules into and out of the cell. The membrane is said to be 'semi-
permeable', in that it can either let a substance (molecule or ion) pass through freely, pass
through to a limited extent or not pass through at all. Cell surface membranes also contain
receptor proteins that allow cells to detect external signaling molecules such as hormones
CYTOSK
KELETON

The cytooskeleton accts to organiize and maiintain the ceell's shape; anchors orgganelles in place; p
helps duuring endocy ytosis, the uptake of external
e maaterials by a cell, and cytokinesiss, the
separatioon of daughteer cells afterr cell division; and movees parts of thhe cell in proocesses of grrowth
and mobbility. The eukaryotic cytoskeletonn is com
mposed of microfilamen
m nts, intermeediate
filamentss and micro otubules. Thhere is a greeat number of proteins associated with them, each
controllinng a cell's structure byy directing, bundling, and a aligningg filaments. The prokarryotic
cytoskeleeton is less well-studiedd but is invoolved in the maintenancce of cell shape, polarityy and
cytokinessis.

GENETIIC MATERIIAL

Two diffferent kinds of genetic material

m existt: deoxyribonucleic acidd (DNA) andd ribonucleicc acid
(RNA). Most
M organissms use DNA A for their loong-term infformation stoorage, but soome viruses (e.g.,
retroviruses) have RNAR as theirr genetic material.
m The biological informationn contained in an
organismm is encoded d in its DNAA or RNA seequence. RN NA is also ussed for inforrmation trannsport
(e.g., mR
RNA) and en nzymatic funnctions (e.g.,, ribosomal RNA)
R in orgganisms that use DNA foor the
genetic code
c itself. Transfer
T RNA A (tRNA) molecules
m aree used to add amino acidds during prrotein
translatioon.

Prokaryootic genetic material is organized in a simplee circular DNA D molecuule (the baccterial
chromosoome) in the nucleoid
n reggion of the cyytoplasm. Euukaryotic geenetic materiial is dividedd into
different,, linear moleecules calledd chromosom mes inside a discrete nuccleus, usuallly with addittional
genetic material
m in so
ome organelles like mitoochondria annd .

A humann cell has geenetic materiial containedd in the cell nucleus (thee nuclear gennome) and in
i the
mitochonndria (the miitochondrial genome). Inn humans thee nuclear gennome is diviided into 23 pairs
of linear DNA moleecules calledd chromosom mes. The mitochondrial
m l genome is a circular DNA
D
moleculee distinct frrom the nucclear DNA. Although the mitochoondrial DNA A is very small
s
comparedd to nuclearr chromosom mes, it codees for 13 prooteins involvved in mitochondrial ennergy
productioon and speciific tRNAs.

Foreign genetic
g mateerial (most commonly
c D
DNA) can allso be artificcially introduuced into thee cell
by a proccess called transfection.
t This can bee transient, if
i the DNA is not insertted into the cell's
genome, or stable, iff it is. Certainn viruses also insert theirr genetic maaterial into thhe genome

ORGAN
NELLES

The hum man body con ntains many different orrgans, such asa the heart, lung, and kidney,
k with each
organ performing a different
d funnction. Cellss also have a set of "littlle organs," called
c organnelles,
that are adapted
a and//or specialized for carrying out one or more vitaal functions.. Both eukarryotic
and prokkaryotic cellss have organnelles but orrganelles in eukaryotes are generallly more com mplex
and may be membran ne bound.
There aree several typpes of organnelles in a cell. Some (ssuch as the nucleus
n and golgi apparratus)
are typiccally solitary
y, while otheers (such ass mitochondrria, peroxisoomes and lyysosomes) caan be
numerouus (hundredss to thousannds). The cyytosol is thee gelatinous fluid that fills
f the celll and
surroundds the organeelles.

Diagram
m of a cell nucleus

Cell nucleus eukaryotees only - A cell's

C c inform
mation centerr, the cell nuucleus is the most
coonspicuous organelle
o fouund in a eukkaryotic cell.. It houses thhe cell's chroomosomes, anda is
thhe place wheere almost alll DNA repliication and RNAR syntheesis (transcripption) occurr. The
nuucleus is sphherical and separated frrom the cytooplasm by a double mem mbrane calleed the
nuuclear envellope. The nuuclear enveloope isolates and protectts a cell's DN NA from vaarious
m
molecules thaat could acccidentally daamage its sttructure or interfere
i witth its processsing.
D
During proceessing, DNA A is transcribbed, or copieed into a speecial RNA, called
c messeenger
R
RNA (mRNA A). This mRN RNA is then transported out of the nucleus,
n wheere it is transslated
innto a specificc protein moolecule. Thee nucleolus is a specializzed region within
w the nuucleus
w
where ribosom me subunitss are assembbled. In prokkaryotes, DN NA processinng takes plaace in
thhe cytoplasm
m.

Mitochondriia and Chloroplasts eukaryotes

M e onnly - the pow
wer generatoors: Mitochoondria
arre self-replicating organnelles that occur
o in varrious numbeers, shapes, and sizes inn the
cyytoplasm off all eukaryottic cells. Mittochondria play
p a criticaal role in gennerating enerrgy in
thhe eukaryotic cell. Mitocchondria gennerate the ceell's energy by
b oxidative phosphorylaation,
using oxygen n to releasee energy sttored in celllular nutrieents (typicallly pertaininng to
glucose) to generate ATP P. Mitochonndria multiply by splittinng in two. Respiration
R occurs
inn the cell mittochondria.
 m of an endoomembrane system
Diagram

Endoplasmicc reticulum
E m eukaryootes only: TheT endoplaasmic reticullum (ER) is the
trransport nettwork for molecules targeted foor certain modificationns and speecific
destinations, as comparedd to moleculles that float freely in thee cytoplasm.. The ER has two
foorms: the ro
ough ER, whhich has riboosomes on its i surface and
a secretes proteins intto the
cyytoplasm, annd the smoooth ER, whiich lacks theem. Smoothh ER plays a role in callcium
seequestration and release.

Golgi appara
G atus eukaaryotes only : The primaary function of the Golggi apparatus is to
prrocess and package
p the macromoleccules such as proteins annd lipids thaat are syntheesized
byy the cell.

Ribosomes: The
R T ribosom me is a large complex off RNA and protein
p moleecules. They each
coonsist of twoo subunits, and
a act as ann assembly liine where RNA
R from thhe nucleus is used
too synthesise proteins from amino aciids. Ribosom
mes can be found
f either floating freeely or
bound to a membrane
m (
(the rough endoplasmat
e tic reticulum
m in eukaryyotes, or thee cell
m
membrane in prokaryotess).

Lysosomes and
L a Peroxisomes eukkaryotes onlyy: Lysosomees contain diigestive enzymes
(aacid hydrolaases). They digest
d excesss or worn-ouut organelles, food particcles, and enggulfed
viruses or baacteria. Peroxxisomes havve enzymes that rid the cell of toxiic peroxides. The
ceell could nott house thesee destructivee enzymes iff they were not
n containedd in a membbrane-
bound system m.

Centrosome the cytoskkeleton orgaaniser: The centrosome

C c p
produces thee microtubulles of
a cell a key y componentt of the cytooskeleton. It directs the transport
t thrrough the ER
R and
thhe Golgi app paratus. Centtrosomes aree composed of two centrrioles, whichh separate during
d
ceell division and help inn the formattion of the mitotic
m spinndle. A singgle centrosomme is
prresent in thee animal cells. They are also
a found inn some funggi and algae cells.
c
 Vacuoles: Vaacuoles storre food and waste. Som
V me vacuoles store extra water. Theyy are
often describ bed as liquidd filled spacce and are surrounded by
b a membrrane. Some cells,
m notably Amoeba, haave contractiile vacuoles,, which can pump waterr out of the cell
most c if
thhere is too much
m water. The vacuolles of eukaryyotic cells are
a usually larger
l in thoose of
plants than annimals.

THE BIO
OLOGICAL
L MEMBR
RANE

Cross secction view of the structuures that can be formed by phospholiipids in aqueeous solutionns

A biologgical membrrane or biom membrane is i an enclosing or separaating membrrane that actss as a

selective barrier, with
hin or arounnd a cell. It coonsists of a lipid
l bilayerr with embeddded proteins that
may connstitute closee to 50% of o membranne content. The T cellularr membranees should noot be
confusedd with isolaating tissuess formed byy layers off cells, suchh as mucouus and baseement
membrannes.

n
Function

Membrannes in cellss typically define

d encloosed spaces or comparrtments in which w cells may
maintain a chemical or biochem mical environnment that diiffers from thet outside. For examplee, the
membranne around peeroxisomes shields
s the reest of the celll from peroxxides, and thhe cell membbrane
separatess a cell from
m its surrounnding medium m. Most orgganelles are defined by such s membrranes,
and are called
c "memb brane-boundd" organelless.

Probablyy the most important

i feeature of a biomembranne is that itt is a selecttively permmeable
structure. This mean ns that the size, chargee, and otherr chemical properties
p o the atomss and
of
moleculees attempting to cross it i will deterrmine whethher they succceed in doiing so. Seleective
permeabiility is essen
ntial for efffective separration of a cell or orgaanelle from its surrounddings.
Biologicaal membranees also have certain mecchanical or elastic properrties.

Particles that are requ

uired for celllular functioon but are unnable to diffuuse freely accross a membbrane
enter throough a mem mbrane transpport protein oro are taken in by meanss of endocytoosis.
TRANSPORT ACROSS THE BIOLOGICAL MEMBRANE

Passive diffusion-movement of solute along the concentration gradient

Facilitated diffusion-movement of solute along the conc gradient with the help of carrier
proteins
Active transport-movement of solute against the conc gradient with the utilization of
energy in the form of ATP

TRANSPORT MODES

Uniport
Symport
Cotransport
Antiport

TRANSPORT OF MACROMOECULES

Endocytosis
Exocytosis

HIGH ENERGY COMPOUNDS

High-energy phosphate can mean one of two things:

The phosphate-phosphate bonds formed when compounds such as adenosine diphosphate

and adenosine triphosphate are created.

The compounds that contain these bonds, which include the nucleoside diphosphates and
nucleoside triphosphates, and the high-energy storage compounds of the muscle, the
phosphagens. When people speak of a high-energy phosphate pool, they speak of the
total concentration of these compounds with these high-energy bonds.

High-energy phosphate bonds are pyrophosphate bonds, acid anhydride linkages, formed by
taking phosphoric acid derivatives and dehydrating them. As a consequence, the hydrolysis of
these bonds is exergonic under physiological conditions, releasing energy.

Energy released by high energy phosphate reactions

Reaction G [kJ/mol]

ATP + H2O ADP + Pi -36.8

ADP + H2O AMP + Pi -36.0

ATP + H2O AMP + PPi -40.6

 PPi + H2O 2 Pi -31.8

AMP + H2O A + Pi -12.6

Except for
f PPi 2 Pi, these reeactions aree, in generall, not alloweed to go unncontrolled in the
human cell
c but aree instead cooupled to other
o processses needingg energy too drive them m to
completion. Thus, high-energy phosphate reaactions can:

prrovide energ gy to cellularr processes, allowing theem to run

coouple processses to a partticular nucleeoside, allow
wing for reguulatory contrrol of the proocess
drrive the reacction to the right,
r by takiing a reversible process and making it irreversible.

The one exception iss of value beecause it alloows a single hydrolysis, ATP + 2H2O AMP + PPi,
to effectiively supply
y the energy of hydrolyssis of two hiigh-energy bonds,
b with the hydrolyssis of
PPi beingg allowed to go to comppletion in a separate
s reacction. The AMP
A is regennerated to AT TP in
two steps, with the equilibrium reaction AT TP + AMP 2ADP, followed byy regeneratioon of
ATP by thet usual meeans, oxidatiive phosphorrylation or other
o energy-producing pathways
p suuch as
glycolysiis.

Often, hiigh-energy phosphate

p boonds are dennoted by the character '~
~'. In this "sqquiggle" notaation,
ATP beccomes A-P~P P~P. The squuiggle notation was inveented by Friitz Albert Lipmann, whoo first
proposedd ATP as th he main eneergy transferr molecule of the cell, in 1941. Itt emphasizees the
special nature of thesse bonds.

ATP is often
o called a high energgy compounnd and its phhosphoanhyddride bonds are a referred to as
high-enerrgy bonds. There
T is notthing speciall about the bonds
b themsselves. Theyy are high-ennergy
bonds in the sense th hat free enerrgy is releassed when they are hydroolyzed, for the t reasons given
g
above. Lipmanns
L teerm high-ennergy bond and his syymbol ~P (ssquiggle P) for a comppound
having a high phosph hate group transfer
t poteential are vivvid, concise, and useful notations. Inn fact
Lipmannns squiggle did much too stimulate interest
i in biioenergeticss.The term 'hhigh energy' with
respect to these bon nds can be misleading,
m b
because the negative freee energy chhange is not due
directly to
t the break king of the bonds them mselves. Thee breaking of these bonds, as withh the
breaking of any bond d, is an endeergonic step (i.e., it absoorbs energy, not releases it). The neggative
free enerrgy change comes
c insteaad from the increased ressonance stabbilization andd solvation ofo the
products relative to thhe reactants.

Adenosin
ne triphosphate
Adenosine-5'-triphosphate (ATP) is a multifunctional nucleoside triphosphate used in cells as a
coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer.
ATP transports chemical energy within cells for metabolism. It is one of the end products of
photophosphorylation and cellular respiration and used by enzymes and structural proteins in
many cellular processes, including biosynthetic reactions, motility, and cell division. One
molecule of ATP contains three phosphate groups, and it is produced by ATP synthase from
inorganic phosphate and adenosine diphosphate (ADP) or adenosine monophosphate (AMP).
The three main ways of ATP synthesis are substrate level phosphorylation, oxidative
phosphorylation in cellular respiration, and photophosphorylation in photosynthesis.

Cyclic adenosine monophosphate (cAMP, cyclicAMP or 3'-5'-cyclic adenosine

monophosphate) is a second messenger important in many biological processes. cAMP is
derived from adenosine triphosphate (ATP) and used for intracellular signal transduction in
many different organisms, conveying the cAMP-dependent pathway
K.ANITA PRIYADHARSHINI

LECTURER

DEPT.OF PHARMACEUTICAL CHEMISTRY

SRM COLLEGE OF PHARMACY