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CHAPTER-I

INTRODUCTION TO BIOCHEMISTRY

CELL AND IT’S 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 µm 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

 

CYTOSKELETON

The cytoskeleton acts to organize and maintain the cell’s shape; anchors organelles in place;
helps during endocytosis, the uptake of external materials by a cell, and cytokinesis, the
separation of daughter cells after cell division; and moves parts of the cell in processes of growth
and mobility. The eukaryotic cytoskeleton is composed of microfilaments, intermediate
filaments and microtubules. There is a great number of proteins associated with them, each
controlling a cell’s structure by directing, bundling, and aligning filaments. The prokaryotic
cytoskeleton is less well-studied but is involved in the maintenance of cell shape, polarity and
cytokinesis.

GENETIC MATERIAL

Two different kinds of genetic material exist: deoxyribonucleic acid (DNA) and ribonucleic acid
(RNA). Most organisms use DNA for their long-term information storage, but some viruses (e.g.,
retroviruses) have RNA as their genetic material. The biological information contained in an
organism is encoded in its DNA or RNA sequence. RNA is also used for information transport
(e.g., mRNA) and enzymatic functions (e.g., ribosomal RNA) in organisms that use DNA for the
genetic code itself. Transfer RNA (tRNA) molecules are used to add amino acids during protein
translation.

Prokaryotic genetic material is organized in a simple circular DNA molecule (the bacterial
chromosome) in the nucleoid region of the cytoplasm. Eukaryotic genetic material is divided into
different, linear molecules called chromosomes inside a discrete nucleus, usually with additional
genetic material in some organelles like mitochondria and .

A human cell has genetic material contained in the cell nucleus (the nuclear genome) and in the
mitochondria (the mitochondrial genome). In humans the nuclear genome is divided into 23 pairs
of linear DNA molecules called chromosomes. The mitochondrial genome is a circular DNA
molecule distinct from the nuclear DNA. Although the mitochondrial DNA is very small
compared to nuclear chromosomes, it codes for 13 proteins involved in mitochondrial energy
production and specific tRNAs.

Foreign genetic material (most commonly DNA) can also be artificially introduced into the cell
by a process called transfection. This can be transient, if the DNA is not inserted into the cell’s
genome, or stable, if it is. Certain viruses also insert their genetic material into the genome

ORGANELLES

The human body contains many different organs, such as the heart, lung, and kidney, with each
organ performing a different function. Cells also have a set of “little organs,” called organelles,
that are adapted and/or specialized for carrying out one or more vital functions. Both eukaryotic
and prokaryotic cells have organelles but organelles in eukaryotes are generally more complex
and may be membrane bound.

 

There are several types of organelles in a cell. Some (such as the nucleus and golgi apparatus)
are typically solitary, while others (such as mitochondria, peroxisomes and lysosomes) can be
numerous (hundreds to thousands). The cytosol is the gelatinous fluid that fills the cell and
surrounds the organelles.

Diagram of a cell nucleus

• Cell nucleus – eukaryotes only – A cell’s information center, the cell nucleus is the most
conspicuous organelle found in a eukaryotic cell. It houses the cell’s chromosomes, and is
the place where almost all DNA replication and RNA synthesis (transcription) occur. The
nucleus is spherical and separated from the cytoplasm by a double membrane called the
nuclear envelope. The nuclear envelope isolates and protects a cell’s DNA from various
molecules that could accidentally damage its structure or interfere with its processing.
During processing, DNA is transcribed, or copied into a special RNA, called messenger
RNA (mRNA). This mRNA is then transported out of the nucleus, where it is translated
into a specific protein molecule. The nucleolus is a specialized region within the nucleus
where ribosome subunits are assembled. In prokaryotes, DNA processing takes place in
the cytoplasm.

• Mitochondria and Chloroplasts – eukaryotes only – the power generators: Mitochondria
are self-replicating organelles that occur in various numbers, shapes, and sizes in the
cytoplasm of all eukaryotic cells. Mitochondria play a critical role in generating energy in
the eukaryotic cell. Mitochondria generate the cell’s energy by oxidative phosphorylation,
using oxygen to release energy stored in cellular nutrients (typically pertaining to
glucose) to generate ATP. Mitochondria multiply by splitting in two. Respiration occurs
in the cell mitochondria.

 

Diagram of an endomembrane system

• Endoplasmic reticulum – eukaryotes only: The endoplasmic reticulum (ER) is the
transport network for molecules targeted for certain modifications and specific
destinations, as compared to molecules that float freely in the cytoplasm. The ER has two
forms: the rough ER, which has ribosomes on its surface and secretes proteins into the
cytoplasm, and the smooth ER, which lacks them. Smooth ER plays a role in calcium
sequestration and release.

• Golgi apparatus – eukaryotes only : The primary function of the Golgi apparatus is to
process and package the macromolecules such as proteins and lipids that are synthesized
by the cell.

• Ribosomes: The ribosome is a large complex of RNA and protein molecules. They each
consist of two subunits, and act as an assembly line where RNA from the nucleus is used
to synthesise proteins from amino acids. Ribosomes can be found either floating freely or
bound to a membrane (the rough endoplasmatic reticulum in eukaryotes, or the cell
membrane in prokaryotes).

• Lysosomes and Peroxisomes – eukaryotes only: Lysosomes contain digestive enzymes
(acid hydrolases). They digest excess or worn-out organelles, food particles, and engulfed
viruses or bacteria. Peroxisomes have enzymes that rid the cell of toxic peroxides. The
cell could not house these destructive enzymes if they were not contained in a membrane-
bound system.

• Centrosome – the cytoskeleton organiser: The centrosome produces the microtubules of
a cell – a key component of the cytoskeleton. It directs the transport through the ER and
the Golgi apparatus. Centrosomes are composed of two centrioles, which separate during
cell division and help in the formation of the mitotic spindle. A single centrosome is
present in the animal cells. They are also found in some fungi and algae cells.

 

• Vacuoles: Vacuoles store food and waste. Some vacuoles store extra water. They are
often described as liquid filled space and are surrounded by a membrane. Some cells,
most notably Amoeba, have contractile vacuoles, which can pump water out of the cell if
there is too much water. The vacuoles of eukaryotic cells are usually larger in those of
plants than animals.

THE BIOLOGICAL MEMBRANE

Cross section view of the structures that can be formed by phospholipids in aqueous solutions

A biological membrane or biomembrane is an enclosing or separating membrane that acts as a
selective barrier, within or around a cell. It consists of a lipid bilayer with embedded proteins that
may constitute close to 50% of membrane content. The cellular membranes should not be
confused with isolating tissues formed by layers of cells, such as mucous and basement
membranes.

Function

Membranes in cells typically define enclosed spaces or compartments in which cells may
maintain a chemical or biochemical environment that differs from the outside. For example, the
membrane around peroxisomes shields the rest of the cell from peroxides, and the cell membrane
separates a cell from its surrounding medium. Most organelles are defined by such membranes,
and are called “membrane-bound” organelles.

Probably the most important feature of a biomembrane is that it is a selectively permeable
structure. This means that the size, charge, and other chemical properties of the atoms and
molecules attempting to cross it will determine whether they succeed in doing so. Selective
permeability is essential for effective separation of a cell or organelle from its surroundings.
Biological membranes also have certain mechanical or elastic properties.

Particles that are required for cellular function but are unable to diffuse freely across a membrane
enter through a membrane transport protein or are taken in by means of endocytosis.

 

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 ΔG [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 PPi → 2 Pi, these reactions are, in general, not allowed to go uncontrolled in the
human cell but are instead coupled to other processes needing energy to drive them to
completion. Thus, high-energy phosphate reactions can:

• provide energy to cellular processes, allowing them to run
• couple processes to a particular nucleoside, allowing for regulatory control of the process
• drive the reaction to the right, by taking a reversible process and making it irreversible.

The one exception is of value because it allows a single hydrolysis, ATP + 2H2O → AMP + PPi,
to effectively supply the energy of hydrolysis of two high-energy bonds, with the hydrolysis of
PPi being allowed to go to completion in a separate reaction. The AMP is regenerated to ATP in
two steps, with the equilibrium reaction ATP + AMP ↔ 2ADP, followed by regeneration of
ATP by the usual means, oxidative phosphorylation or other energy-producing pathways such as
glycolysis.

Often, high-energy phosphate bonds are denoted by the character ‘~’. In this “squiggle” notation,
ATP becomes A-P~P~P. The squiggle notation was invented by Fritz Albert Lipmann, who first
proposed ATP as the main energy transfer molecule of the cell, in 1941. It emphasizes the
special nature of these bonds.

ATP is often called a high energy compound and its phosphoanhydride bonds are referred to as
high-energy bonds. There is nothing special about the bonds themselves. They are high-energy
bonds in the sense that free energy is released when they are hydrolyzed, for the reasons given
above. Lipmann’s term “high-energy bond” and his symbol ~P (squiggle P) for a compound
having a high phosphate group transfer potential are vivid, concise, and useful notations. In fact
Lipmann’s squiggle did much to stimulate interest in bioenergetics.The term ‘high energy’ with
respect to these bonds can be misleading, because the negative free energy change is not due
directly to the breaking of the bonds themselves. The breaking of these bonds, as with the
breaking of any bond, is an endergonic step (i.e., it absorbs energy, not releases it). The negative
free energy change comes instead from the increased resonance stabilization and solvation of the
products relative to the reactants.

Adenosine 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