Medical biochemistry

Introduction
 Lecture objectives

• Explain what biochemistry and appreciate its

central role in the life sciences.
• List the principles of biochemistry
• Understand the relationship of biochemistry to
health and disease and to medicine.
• know some important organelles of the cell and
their biochemical functions
• Explain the important bio-molecules found in the
cell
 References
1. Champ and Harvey, Lippincott’s illustrated
review of biochemistry. 4th edi.
2. Marks' Essential Medical Biochemistry 2nd
edition (2007). Lippincott Williams & Wilkins
3. N. V. Bhagavan. Medical Biochemistry, 5th,
2005. San Diego, California. An Imprint of
Elsevier.
4. Harper’s biochemistry 31th edition (2009)
5. http://themedicalbiochemistrypage.org
/
 What is biochemistry?
• Defined as the science of the chemical basis of
life
• Meaning; the study of the chemical
constituents of living cells and of the reactions
and processes they undergo
Thus: covers large areas of cell biology,
molecular biology and molecular genetics.
 Principles of biochemistry
1. Cells are highly organized and constant source of energy
is required to maintain the ordered state
2. Living process contains thousands of chemical
reactions, precise integration and regulation of this
reactions is required to maintain life
3. Certain important rxns is found in almost all organisms
4. All organisms use the same type of molecules; CHO,
proteins, lipids and nucleic acids
5. Instruction for reproduction, growth and development for
each organism is encoded in their DNA
• The major objectives of biochemistry is
 To understand of all of the chemical processes associated
with living
 To maintain health and understand diseases and
treat them effectively
• A Knowledge of Biochemistry Is Essential to All Life Sciences.
E.g.
 Physiology: overlaps with biochemistry
 Immunology: employs numerous biochemical techniques
 Pharmacology: biochemistry helps to understand the action of
new drugs
 Pathology : uses biochemical approaches to study disease such as
cancer
 Biochemistry & Medicine
 The two major concerns for workers in the health sciences
are;
 The understanding and maintenance of health.
 The understanding and effective treatment of
diseases.
 Biochemistry impacts enormously on both of these fundamental
concerns of medicine
 In fact, the interrelationship of biochemistry and medicine is a wide,
two-way street.
 Advances in biochemical knowledge have illuminated many areas of
medicine.
 Conversely, the study of diseases has often revealed previously
unsuspected aspects of biochemistry.
 Biochemistry & Medicine

Biochemical approaches are often fundamental in

illuminating the causes of diseases and in designing
appropriate therapies.
In addition, biochemistry is concerned with optimal dietary
intake of a number of chemicals, which is very important to
maintain health and prevent disease
 Biochemical processes for life
• The maintenance of health requires optimal
dietary intake of a number of chemicals; vitamins,
certain amino acids and fatty acids, various
minerals, and water.
• maintain health and forestall disease, or
preventive medicine, includes nutritional
approaches to the prevention of diseases such as
atherosclerosis and cancer
 Biochemical processes for life

Causes of Diseases with Biochemical Basis

• many diseases are manifestations of abnormalities in
genes, proteins, chemical reactions, or biochemical
processes
• Electrolyte imbalance, defective nutrient ingestion or
absorption, hormonal imbalances, toxic chemicals or
biologic agents, and DNA-based genetic disorders are
some causes of diseases
• Biochemical research continues to combat those
challenges
 The human genome project
• The sequence of the entire human genome was completed
in 2003,
• Revealed previously unknown genes and their products
• New insights have been gained concerning procedures for
identifying disease-related genes.
• Understanding human health and disease continue to be
made by mutation of the genomes of model organisms such
as yeast and of eukaryotes
• Help humans by providing clues to curing human diseases
such as cancer and Alzheimer disease
 The human genome project
Omics; comprehensive study of the structures and
functions of the molecules
e.g. The products of genes (RNA molecules and
proteins) are being studied using the techniques of
transcriptomics and proteomics.
Other -omics fields include glycomics, lipidomics,
metabolomics, nutrigenomics, and
pharmacogenomics
Some uses of biochemical investigations
 What are cells?

• Membrane bounded compartments filled with

chemicals

• Fundamental structural and functional units of living

creatures

• Machines with complex regulation and behaviors;

based on networks of chemical reactions called

pathways
24/04/2025 Molecular Cell Biology 15
• Endowed with the ability to create copies of
• The cell is the smallest unit of
life.
• All organisms are composed one
or more cells.
• New cells arise from previously
existing cells.
 Characteristics of the cell
• Grow
• Reproduce
• Use energy
• Adapt
• Respond to their environment
 Cells
Each cell has four common components:
– Plasma membrane
– Region containing DNA
– Cytoplasm
– Biochemical molecules & biochemical pathways
 Cells May be Prokaryotic or eukaryotic
Prokaryotes(bacteria) lack organelles
Contains
 Nucleoid region that contain DNA
 Cell membrane & cell wall
 Ribosomes to make proteins in their cytoplasm
Eukaryotes (plants, fungi, & animals)
contain 3 basic cell structures:
 Nucleus
 Cell Membrane
 Cytoplasm with organelles
Eukaryotic cell
 The Cytoplasm & cytosol
Cytoplasm
• The material or protoplasm
within a living cell, excluding
the nucleus
Cytosol
• The aqueous component of
the cytoplasm of a cell, within
which various organelles and
particles are suspended.
 Plasma membrane

• Cell membrane separates living cell from nonliving

surroundings
Thin barrier = 8nm thick
• Controls traffic in & out of the cell
 Selectively permeable
Allows some substances to cross more easily than others
• Hydrophobic vs hydrophilic
• Made of phospholipids, proteins & other
macromolecules
 Phospholipids
Phosphate
• Fatty acid tails
– hydrophobic
• Phosphate group head
Fatty acid
– hydrophilic
• Arranged as a bilayer

Aaaah,
one of those
structure–function
examples
 Membrane fat composition varies
• Fat composition affects flexibility
membrane must be fluid & flexible
• About as fluid as thick salad oil
 % unsaturated fatty acids in phospholipids
• keep membrane less viscous
 cholesterol in membrane increases its flexibility
 Membrane Proteins
• Proteins determine membrane’s specific functions
 cell membrane & organelle membranes each have unique
collections of proteins
• Membrane proteins:
 Peripheral proteins
• loosely bound to surface of membrane
• cell surface identity marker (antigens)
 Integral proteins
• penetrate lipid bilayer, usually across whole membrane
• Transmembrane protein
• transport proteins
– channels, carrier
 Nucleus

• Double membrane surrounding the chromosomes and

the nucleolus.
• Pores allow specific communication with the
cytoplasm.
• The nucleolus is a site for RNA synthesis
 Mitochondrion

• Surrounded by a double membrane with series of

folds called cristae.
• Functions in energy production through metabolism
(generate high energy molecule, ATP)
• Interconnects the metabolic processes of
carbohydrate, lipid, and amino acid catabolism
• Contains its own DNA,
Mitochondrion
 Endoplasmic reticulum (ER)

A network of interconnected membranes forming

channels within the cell.
Two types
1. Rough endoplasmic reticulum
Covered with ribosomes which are in the process of
synthesizing proteins.
2. Smooth endoplasmic reticulum (SER
A site for synthesis and metabolism of lipids
contains enzymes for detoxifying chemicals including
drugs and pesticides.
Endoplasmic reticulum (ER
 Golgi apparatus

• A series of stacked membranes.

• Receives proteins from the ER and extrudes them in
the direction of the cell membrane.
Function as
 Protein processing
 Production, processing, and destruction of lipid
 Production of lysosomes
 Lysosomes are formed when pieces of the Golgi
apparatus are pinched off as a sac containing the
lysozymes
Golgi apparatus
- Peroxisomes
 contain oxidative enzymes that form and
degrade hydrogen peroxide

FA ------ H2O2 --- water + oxygen

 Cytoskeleton

- Provides strength and structure to the cell

- Provides fundamental mechanistic components needed for
movement
- Three main types
 Actin (microfilament): generates contractile forces (i.e.
muscles); thinnest filaments
 Intermediate filaments: strengthen the cell mechanically
 Microtubules: hollow tubes that direct movement of
duplicated chromosomes in dividing cells
Cytoskeleton
 Cells
• The cell it self made from bio-molecules
Protein………17%
Fat……………..13.8%
CHO………….1.5%
H2O…………..61.6%
Minerals and vitamins…6.1%
Cell Signaling
 Introduction
• Cell-to-cell communication is absolutely essential for
multicellular organisms and is also important for many
unicellular organisms.
– Cells must communicate to coordinate their activities.
• Biologists have discovered some universal mechanisms
of cellular regulation, involving the same small set of
cell-signaling mechanisms.

• Cells may receive a variety of signals, chemical signals,

electromagnetic signals, and mechanical signals.

• Signal-transduction pathway: The process by which a signal on a

cell’s surface is converted into a specific cellular response.
The growth of multicellular organisms is regulated
by more than just nutrient availability

NUTRIENTS
unicellular
eukaryote

NUTRIENTS

multicellular
eukaryote

a edigner
Cells in multicellular eukaryotes require
permission signals from growth factors

NUTRIENTS

NUTRIENTS

a edigner
 Some growth factors
• EGF - epidermal growth factor
• FGF - fibroblast growth factor
• NGF - nerve growth factor
• PDGF - platelet-derived growth factor
• Insulin-like GF

All of these bind to a class of receptors known as

“Receptor Kinases”
 Cell signaling pathways regulate:

cell cycle- proliferation

cytoskeleton- migration

transcription- differentiation

membrane traffic- exocytosis

cell survival and death- apoptosis

development- body plan

Cell Signaling Is Central to Modern Medicine

Cancer Diabetes

Steroids
AIDS

Viagra
Cholera Angina

Alzheimer
Whooping cough ….among others
 General Principles of Cell Signaling

• Cell communication occurs at various distances

• Numerous signaling molecules (ligands) and
receptors but limited signaling pathways
• Ligand-receptor interactions are specific
• Formation of signaling complex
• Some intracellular signaling proteins function as
molecular switches
 Talking to cells, both near and
far…
• Multicellular organisms can also release signaling
molecules that target other cells.
– Some transmitting cells release local regulators that
influence cells in the local vicinity.
– In synaptic signaling, a nerve cell produces a
neurotransmitter that diffuses to a single cell that is almost
touching the sender.
– Plants and animals use hormones to signal at greater
distances.
– Cells may communicate by direct contact.
Forms of intercellular signaling.

(A) Contact-dependent signaling requires cells to be

in direct membrane-membrane contact.

(B) Paracrine signaling depends on signals that are

released into the extracellular space and act locally
on neighboring cells.

(C) Synaptic signaling is performed by neurons that

transmit signals electrically along their axons and
release neurotransmitters at synapses, which are
often located far away from the cell body.

(D) Endocrine signaling depends on endocrine cells,

which secrete hormones into the bloodstream that
are then distributed widely throughout the body.
Many of the same types of signaling molecules are
used in paracrine, synaptic, and endocrine signaling;
LE 11-2
Exchange of Receptor a factor
mating factors

a a

Yeast cell, a factor Yeast cell,

mating type a mating type a

Mating

a a

New a/a cell

a/a
LE 11-3
Plasma membranes

Gap junctions Plasmodesmata

between animal cells between plant cells
Cell junctions

Cell-cell recognition
 Seven Steps in Cell-to-cell Communication
(1) synthesis of the signaling molecule by the signaling cell
(2) release of the signaling molecule by the signaling cell
(3) transport of the signal molecule to the target cell
(4) detection of the signal by a specific receptor protein
(5) initiation of intracellular signal-transduction pathways
(6) a change in cellular metabolism, function, or
development of the target cell
(7) removal of the signal, which usually terminates the
cellular response
Signal molecules and Receptor Proteins

• A cell targeted by a particular chemical signal

has a receptor protein that recognizes the
signal molecule.
– Recognition occurs when the signal binds to a
specific site on the receptor because it is
complementary in shape.
• When ligands attach to the receptor protein,
the receptor typically undergoes a change in
shape.
– This may activate the receptor so that it can interact
with other molecules.
– For other receptors this leads to the collection of
receptors.
Cell Signaling
• Forms of signaling
molecules
– Gasses
• NO
• CO
– Steroid Hormones
• Testosterone
• Estradiol
• Progesterone
• Glucocorticoids
– Cortisol
• Mineralocorticoids
– Aldosterone

Topic 14-1 58
Cell Signaling
• Forms of signaling molecules
– Neurotransmitters

Topic 14-1 59
Cell Signaling
• Forms of signaling
molecules
– Peptide Hormones and
Growth Factors

Topic 14-1 60
 Hormones Can Be Classified Based on Their
Solubility and Receptor Location

Most hormones fall into three broad categories:

(1) small lipophilic molecules that diffuse across the

plasma membrane and interact
with intracellular receptors

(2) hydrophilic or (3) lipophilic molecules that bind

to cell-surface receptors
Ligands bind to either cell-
surface receptors or
intracellular receptors.

hydrophilic signal molecules

bind to cell-surface receptors,
which in turn generate one or
more signals inside the target
cell.

Hydrophobic and small signal

molecules diffuse across the
plasma membrane and bind
to receptors inside the target
cell either in the cytosol or in
the nucleus
Cell surface receptor and signaling

The process in which cells sense the extracellular stimuli

through membranous transduce the signals via
intracellular molecules, and thus regulate the biological
function of the cells
cell surface receptor and second messenger system
 Singnalsome
Signaling molecules interact with each other to form large
complexes, and most of those complexes do not diffuse in the
cytoplasm, but rather are attached to cell membranes.

The complex is called signalsome or transducisome.

Among components of a signalsome, a protein that binds to
more than one protein and has no enzymatic activity is defined
as a scaffold protein, because the primary function of such a
molecule is to provide other components with a framework on
which they efficiently work.
Singnalsome
• The signalsome that makes up each
signalling system has a normal operational
range (green curve) over which it responds
to changes in stimulus

• If the signalsome is remodelled, this

sensitivity will change such that the
signalsome becomes either
• sensitized (red curve) or desensitized (blue
curve).
• Such shifts in sensitivity may be responsible
for various disease states.
Relationship between stimulus strength and signalling responses
for normal and remodelled signalosome .
 Intracellular Receptors
• Some receptor proteins are intracellular, found in
the cytosol or nucleus of target cells
• Small or hydrophobic chemical messengers can
readily cross the membrane and activate receptors
• Examples of hydrophobic messengers are the
steroid and thyroid hormones of animals
• An activated hormone-receptor complex can act as
a transcription factor, turning on specific genes
LE 11-6
Hormone EXTRACELLULAR
(testosterone) FLUID The steroid
hormone testosterone
passes through the
plasma membrane.

Plasma
membrane Testosterone binds
Receptor to a receptor protein
protein in the cytoplasm,
Hormone- activating it.
receptor
complex

The hormone-
receptor complex
enters the nucleus
and binds to specific
genes.
DNA

mRNA The bound protein

stimulates the
transcription of
the gene into mRNA.
NUCLEUS New protein

The mRNA is
translated into a
specific protein.
CYTOPLASM
Cell function depended on multiple extracellular signals. Each cell
type displays a set of receptors that enables it to respond to a
corresponding set of signal molecules produced by other cells. These
signal molecules work in combinations to regulate the behaviour of
the cell. As shown here, an individual cell requires multiple signals to
survive (blue arrows) and additional signals to divide (red arrow) or
differentiate (green arrows). If deprived of appropriate survival
 Responses to cell signaling
Something
happens
biochemically
• Gene expression is altered at the level of
transcription, RNA processing or translation
• Enzyme activities are altered
• Protein-protein interactions are induced or
inhibited
• The localization of certain proteins and other stuff
is altered

©2002 Lee Bardwell

 SUMMARY
 Extracellular signaling molecules regulate interaction between
unicellular organisms and are critical regulators of physiology and
development in multicellular organisms.

 There are many different types of signals, including

membrane-anchored and secreted proteins and peptides,
small lipophilic molecules (e.g., steroid hormones, thyroxine),
small hydrophilic molecules derived from amino acids (e.g.,
catecholamines), and gases. Signals can act at short range,
long range, or both
 The multitude of cell-surface receptors fall into four main
classes: G protein – coupled receptors, ion-channel receptors,
receptors linked to cytosolic tyrosine kinases, and receptors
with intrinsic catalytic activity
 Binding of extracellular signaling molecules to cell-surface
receptors trigger intracellular pathways that ultimately
modulate cellular metabolism, function, or development.

 The level of second messengers, such as Ca2+, cAMP, and

IP3 are modulated in response to binding of ligand to cell-
surface receptors. These intracellular signaling molecules, in
turn, regulate the activities of enzymes and nonenzymatic
proteins.
 Conserved proteins that act in many signal-transduction
pathways include GTPase switch proteins (trimeric G proteins
and monomeric Ras-like proteins), protein kinases, and
adapter proteins . The latter coordinate the formation of
multicomponent signaling complexes.

 Extracellular signals are often integrated into complex

regulatory networks in which the synthesis, release, and
degradation of hormones are precisely regulated.
 THE END
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