Medical Biochemistry

Introduction, Organelles, Water and Acid Base balance

Biochemistry definition
• Molecular basis of life
• Chemistry of life
Introduction
• Biochemistry has developed as an offshoot of organic chemistry, and
this branch was often referred as "physiological chemistry". The term
"Biochemistry" was coined by Neuberg in 1903 from Greek words,
bios (= life) and chymos (= juice).
Introduction
• Biochemistry is the language of biology. The tools for research in all
the branches of medical science are based on principles of
biochemistry
Introduction
• Classical Biochemistry- Studies about the quantitative and qualitative
aspects of cells
• Modern Biochemistry- Studies about chemical reactions in cells
Biochemistry and Medicine
• Biochemistry and medicine enjoy a mutually cooperative relationship.
Biochemical studies have illuminated many aspects of health and
disease, and the study of various aspects of health and disease has
opened up new areas of biochemistry.
Biochemistry and Medicine
• Biochemistry makes significant contributions to the fields of cell
biology, physiology, immunology, microbiology, pharmacology, and
toxicology, as well as the fields of inflammation, cell injury, and
cancer.
• The two major concerns for workers in the health sciences— and
particularly physicians—are the understanding and maintenance of
health and the understanding and effective treatment of disease.
Biochemistry impacts both of these fundamental concerns, and the
interrelationship of biochemistry and medicine is a wide, two-way
street.
• The World Health Organization (WHO) defines health as a state of
“complete physical, mental, and social well-being and not merely the
absence of disease and infirmity.” From a biochemical viewpoint,
health may be considered that situation in which all of the many
thousands of intra- and extracellular reactions that occur in the body
are proceeding at rates commensurate with the organism’s survival
under pressure from both internal and external challenges
• Apart from infectious organisms and environmental pollutants, many
diseases are manifestations of abnormalities in genes, proteins,
chemical reactions, or biochemical processes, each of which can
adversely affect one or more critical biochemical function
Scope of Medical Biochemistry
• Understanding disease processes
• Disease diagnosis
• Therapy
• Drug design
• Personalized medicine
Causes of disease
• Genetic
• Immunologic
• Biological
• Trauma or Injury
• Nutritional Imbalance
Introduction
• More than 99% of the human body is composed of 6 elements, i.e.
oxygen, carbon, hydrogen, nitrogen, calcium and phosphorus.
• Molecular structures in organisms are built from 30 small precursors,
sometimes called the alphabet of biochemistry.
Introduction
• In living organisms the biomolecules are ordered into a hierarchy of
increasing molecular complexity. These biomolecules are covalently
linked to each other to form macromolecules of the cell, e.g. glucose
to glycogen, amino acids to proteins, etc. Major complex biomolecules
are Proteins, Polysaccharides, Lipids and Nucleic acids.
Introduction
• The macromolecules associate with each other by noncovalent forces
to form supramolecular systems, e.g. ribosomes, lipoproteins.
• Finally, at the highest level of organization in the hierarchy of cell
structure, various supramolecular complexes are further assembled
into cell organelle.
Criteria for life
• Microscopic Subcellular components
• Have a mechanism to derive and use energy
• Genetic material
• Self-assembly and reproduction
Inputs for life
• Food- carbohydrates, lipids, proteins, alcohol and ketone bodies,
minerals and vitamins
• Water- solvent of life
• Air – most amount of oxygen is used for oxidative phosphorylation
Macromolecules and Micro molecules
• Lipids
• Proteins
• Carbohydrates
• Nucleic acids
• Vitamins
• Minerals
Cell theory
• Cells make up all living matter
• All cells arise from other cells
• The genetic information required during the maintenance of existing
cells and the production of new cells passes from one generation to the
other next generation
• The chemical reactions of an organism that is its metabolism, both
anabolism and catabolism, takes place in the cells.
Cell and subcellular organelles
Nucleus
• Nuclear envelope
• Nuclear pore complexes
• Chromatin
• Nucleolus
• nucleoplasm
Nucleus
• It is the most prominent organelle of the cell. All cells in the body
contain nucleus, except mature RBCs in circulation. The uppermost
layer of skin also may not possess a readily identifiable nucleus. In
some cells, nucleus occupies most of the available space, e.g. small
lymphocytes and spermatozoa.
Nucleus
• Nucleus is surrounded by two membranes: the inner one is called
perinuclear membrane with numerous pores. The outer membrane is
continuous with membrane of endoplasmic reticulum.
• Nucleus contains the DNA, the chemical basis of genes which governs
all the functions of the cell
• The very long DNA molecules are complexed with proteins to form
chromatin and are further organized into chromosomes.
• DNA replication and RNA synthesis (transcription) are taking place
inside the nucleus.
Nucleus
• The vast amount of cellular deoxyribonucleic acid (DNA) is located
in the nucleus as a DNA– protein complex, chromatin, that is
organized into chromosomes. DNA is the repository of genetic
information and the importance of the nucleus in cell division and for
controlling phenotypic expression of genetic information is well
established. Biochemical reactions in the nucleus are replication of
DNA during mitosis, repair of DNA following damage
Nucleolus
• In some cells, a portion of the nucleus may be seen as lighter shaded
area; this is called nucleolus. This is the area for RNA processing and
ribosome synthesis. The nucleolus is very prominent in cells actively
synthesizing proteins.
Endoplasmic reticulum
• It is a network of interconnecting membranes enclosing channels or
cisternae, that are continuous from outer nuclear envelope to outer
plasma membrane. Under electron microscope, the reticular
arrangements will have railway track appearance
ER
• It is very prominent in cells actively synthesizing proteins, e.g.
immunoglobulin secreting plasma cells. The proteins, glycoproteins
and lipoproteins are synthesized in the ER.
• Detoxification of various drugs is an important function of ER.
Microsomal cytochrome P-450 hydroxylates drugs such as
benzpyrine, aminopyrine, aniline, morphine, phenobarbitone, etc.
• When cells are fractionated, the complex ER is disrupted in many
places. They are automatically re-assembled to form microsomes
Golgi complex
• The Golgi organelle is a network of flattened smooth membranes and
vesicles. It may be considered as the converging area of endoplasmic
reticulum
• Golgi apparatus is composed of cis, medial and trans cisternae.
Glycoproteins are generally transported from ER to cis Golgi
(proximal cisterna), then to medial Golgi (intermediate cisterna) and
finally to trans Golgi (distal cisterna) for temporary storage. Trans
Golgi are particularly abundant with vesicles containing glycoproteins.
Golgi apparatus
• Main function of Golgi apparatus is protein sorting, packaging and
secretion.
Fate of finished products
• The finished products may have any one of the following destinations:
• They may pass through plasma membrane to the surrounding medium.
This forms continuous secretion, e.g. secretion of immunoglobulins by
plasma cells.
• They reach plasma membrane and form an integral part of it, but not
secreted.
• They are formed into a secretory vesicle, where these products are
stored for a longer time. Under appropriate stimuli, the contents are
secreted. E.g. Trypsinogen
• The synthesized materials may be collected into lysosome packets.
Mitochondrion
• Mitochondrion is the power house of cell
• Number
• They are spherical, oval or rod-like bodies, about
• 0.5–1 μm in diameter and up to 7 μm in length
Functions
• Energy production
• Encode amino acids
• Detoxification
• Steroidogenesis
• Mitochondria also contain specific DNA. The integral inner
membrane proteins, are made by mitochondrial protein synthesizing
machinery. However the majority of proteins, especially of outer
membrane are synthesized under the control of cellular DNA.
Mitochondria
• Cristae
• Cardiolipin
Plasma membrane
Functions
• The plasma membrane of every cell has a unique role in maintenance
of that cell's integrity. One surface is in contact with a variable
external environment and the other with a relatively constant
environment provided by the cell's cytoplasm.
Functions
• A major role of the plasma membrane is to permit entrance of some
substances but exclude many others. With cytoskeletal elements, the
plasma membrane is involved in cell shape and movements. Through
this membrane cells communicate; the membrane contains many
specific receptor sites for chemical signals, such as hormones, released
by other cells
• Fluidity of cellular membranes responds to variations in diet and
physiological states. Increased release of reactive oxygen species
(ROS), increase in cytosolic calcium and lipid peroxidation have been
found to adversely affect membrane fluidity.
• Membranes are mainly made up of lipids, proteins and small amount
of carbohydrates. The contents of these compounds vary according to
the nature of the membrane
Peroxisome
 The peroxisomes have a granular matrix. They are of 0.3–1.5 μm in
diameter. They contain peroxidases and catalase. They are prominent
in leukocytes and platelets.
Catalase and peroxidase are the enzymes present in peroxisomes
which will destroy the unwanted peroxides and other free radicals.
LYSOSOMES

• Lysosomes are tiny organelles. Solid wastes of a township are usually

decomposed in incinerators. Inside a cell, such a process is taking
place within the lysosomes. They are bags of enzymes.
• The lysosomal enzymes have an optimum pH around 5.
• These enzymes are
• a. Polysaccharide hydrolysing enzymes (alpha-glucosidase, alpha-
fucosidase, beta-galactosidase, alpha mannosidase, beta-glucuronidase,
hyaluronidase, aryl sulfatase, lysozyme)
• b Protein hydrolysing enzymes (cathepsins, collagenase, elastase,
peptidases)
• c. Nucleic acid hydrolysing enzymes (ribonuclease, deoxyribonuclease)
• Lipid hydrolysing enzymes (fatty acyl esterase, phospholipases)
Metabolic functions or organelles
Objectives
• At the end of the lesson students will be able to
• List the properties of water
• Define biologic functions of water
• Discuss Acid base balances
Water

• Approximately 60% of our body is water. It acts as a solvent for the substances we
need, such as K+, glucose, adenosine triphosphate (ATP), and proteins. It is
important for the transport of molecules and heat.
• Water is distributed between intracellular and extracellular compartments, the
latter comprising interstitial fluids, blood, and lymph.
• 75% in children
• Fairly constant level of water in the body
Properties
• Dipole
• High melting point
• High boiling point
• High heat capacity
• Exist in three states
Functions
• Bathes our cells
• Dissolves and transport compounds
• Medium of transport
• Separate charged molecules
• Dissipates heat
• Insulation
• Participates in chemical reactions
• Digestion
• Respiration
• Lubricant
• Support
• Few gifted properties of water make it the most preferred medium for
all cellular reactions and interactions.
• a. Water is a polar molecule. Molecules with polar bonds that can
easily form hydrogen bonds with water can dissolve in water and are
termed “hydrophilic”.
• b. It has immense hydrogen bonding capacity both with other
molecules and also the adjacent water molecules. This contributes to
cohesiveness of water.
• c. Water favors hydrophobic interactions and provides a basis for
metabolism of insoluble substances.
• ICF is mostly water and is rich in K+, Mg++, HPO4 2-, SO4 2-, and
protein anions.
• ECF contains more Na+, Cl-, HCO3 -, and Ca++.
Osmolality and water movement
• Water distributes between the different fluid compartments
according to the concentration of solutes, or osmolality, of
each compartment. The osmolality of a fluid is proportional
to the total concentration of all dissolved molecules,
including ions, organic metabolites, and proteins, and is
usually expressed as milliosmoles (mOsm)/kg water
• Osmotic pressure
• Hydrostatic pressure
Water balance
• Kidney
• Thirst
• Skin
• Lung
• Food
• Beverages
• Feces
ADH
Acid and Bases
• Acids are compounds that donate a hydrogen ion (H+) to a solution,
and bases are compounds (such as the OH− ion) that accept hydrogen
ions. Water itself dissociates to a slight extent, generating H+, which
are also called protons, and hydroxide ions (OH−)
• Most H+ comes from metabolism -- glycolysis, oxidation of fatty
acids and amino acids, and hydrolysis of proteins.
• Homeostasis of pH in body fluids is regulated by acid-base buffer
systems (primary control), respiratory centers in brain stem, and by
kidney tubule secretion of H+.
Acids
• Metabolism
• Organic
• Inorganic
• Most are weak acids
Acids
• Carboxylic acids- ketone bodies acetoacetic acid and β-hydroxybutyric
acid
• Phosphoric acid- Nucleic acids
• Sulfuric acid- cysteine and methionine
Types of acids
• Based on property
• Volatile acids
• Fixed acids
• Based on component
• Organic acids
• Inorganic acids
Buffers
• Chemical buffers
• Lung
• Kidneys
• Liver
• Bone
Bicarbonate Buffer System
• The most important buffer system in the plasma is the bicarbonate-
carbonic acid system (NaHCO3/H2CO3). It accounts for 65% of
buffering capacity in plasma and 40% of buffering action in the whole
body.
• ii. The base constituent, bicarbonate (HCO3 –), is regulated by the
kidney (metabolic component).
• While the acid part, carbonic acid (H2CO3), is under respiratory
regulation (respiratory component).
• The normal bicarbonate level of plasma is 24 mmol/liter. The normal
pCO2 of arterial blood is 40 mm of Hg. The normal carbonic acid
concentration in blood is 1.2 mmol/L. The pKa for carbonic acid is 6.1.
Substituting these values in the Henderson- Hasselbalch's equation,
• pH = pKa + log [HCO3–]
• [H2CO3]
• 7.4 = 6.1 + log 24
• 1.2
• = 6.1 + log 20 = 6.1 + 1.3
RESPIRATORY REGULATION OF pH

• The Second Line of Defense

• i. This is achieved by changing the pCO2 (or carbonic acid, the
denominator in the equation). The CO2 diffuses from the cells into the
extracellular fluid and reaches the lungs through the blood.
• ii. The rate of respiration (rate of elimination of CO2) is controlled by
the chemoreceptors in the respiratory center which are sensitive to
changes in the pH of blood.
RENAL REGULATION OF pH
• Normal urine has a pH around 6; this pH is lower than that of
extracellular fluid (pH = 7.4). This is called acidification of urine. The
pH of the urine may vary from as low as 4.5 to as high as 9.8,
depending on the amount of acid excreted. The major renal
mechanisms for regulation of pH are:
• A. Excretion of H+
• B. Reabsorption of bicarbonate (recovery of bicarbonate)
• C. Excretion of titratable acid (net acid excretion)
• D. Excretion of NH4+ (ammonium ions).
Factors Affecting Renal Acid Excretion
• Increased filtered load of bicarbonate
• Decrease in ECF volume
• Decrease in plasma pH
• Increase in pCO2 of blood
• Hypokalemia
• Aldosterone secretion
Hemoglobin
•TRANSPORT OF CARBON DIOXIDE
•At rest, about 200 ml of CO is produced per minute
2

•in tissues. The CO is carried by the following 3 ways.

2

•1: Dissolved Form

•About 10% of CO is transported as dissolved form.
2

•CO + H O H CO HCO + H
2 2 2 3 3– +

•The hydrogen ions thus generated, are buffered by the buffer systems
of plasma.
2. Isohydric transport
Carriage as Carbamino-Hemoglobin

• The rest 15% of CO is carried as carbaminohemoglobin, without much

2

change in pH. A fraction of CO that enters into the red cell is bound to
2

Hb as a carbamino complex.
• R–NH + CO --------- R–NH–COOH
2 2

• The N-terminal amino group (valine) of each globin chain forms

carbamino complex with carbon dioxide. Deoxy-hemoglobin binds
CO in this manner more readily than oxy-hemoglobin.
2
Buffers
• Acidosis
• If the pH is below 7.38, it is called acidosis. Life is threatened when
the pH is lowered below 7.25. Acidosis leads to CNS depression and
coma. Death occurs when pH is below 7.0.
• Alkalosis
• When the pH is more than 7.42, it is alkalosis. It is very dangerous if
pH is increased above 7.55.
• Alkalosis induces neuromuscular hyperexcitability and tetany. Death
occurs when the pH is above 7.6.