DR.
VIJETHA SHENOY BELLE
Associate Professor & In-charge Clinical Biochemistry Laboratory
Department Of Biochemistry
KMC Manipal
OVERVIEW
imparts competency based education
conduct good quality research- ICMR projects
provide high standard of diagnostic services
RECOMMENDED BOOKS
Textbook of Biochemistry, D.M Vasudevan,
Sreekumari & K. Vaidyanathan
Biochemistry by [Link]
Modes of teaching
Lectures (Theory classes)
Small group teaching (SGT)
Self directed learning (SDL)
DOAP (Practical)
Early clinical exposure
• A 100 page long book for writing SGT, SDL & ECE
• Record book for practical
BIOCHEMISTRY
Carl A Neuberg
1903
BIOCHEMISTRY
“BIOS” = Life
The chemistry of “LIFE”
The science concerned with the
chemical basis of life
BIOCHEMISTRY
Our body is a huge LABORATORY
LIFE
What we call LIFE is due to
the biochemical reaction taking
place in the body
Why have so many reactions?
To give ENERGY
To GROW
To REPRODUCE
To heal and repair worn out
Tissues
To keep the body healthy
To fight against disease causing
organisms
Basic elements in the cell
Carbon
Hydrogen
Oxygen
Nitrogen
Phosphorus
Sulphur,
Calcium,
Magnesium
Livi
ng
Basic molecules in the cell
Carbohydrates
Lipids
Proteins
Nucleic Acids
Water
Living or
non-living???
CEL
L
B S of 1 0 m o n t h old
B o y
Living or non-living?????
BIOCHEMISTRY
Human Biochemistry
Plant Biochemistry
Microbial Biochemistry
Biotechnology
Genomics
Proteomics
Bioinformatics
Our focus in MBBS
HUMAN BIOCHEMISTRY and NUTRITION
• 1944—DNA is shown to be the
hereditary material
• 1953—Concept of the double helix is
posited
• 1966—The genetic code is solved
• 1972—Recombinant DNA
technology
is developed
• 2003—Sequencing of the first
human
Clinical Biochemistry
Applies basic biochemistry and analytical chemistry to
medical diagnosis, treatment and management.
Biochemical diagnosis
Heart Disease
Liver Disease
Detection of cancer
Electrolyte imbalance
Blood Gas Analysis
Hemoglobin abnormalities
Molecular biology diagnostics
Metaphase
Karyotype
Learning objective
Correlate biochemical pathogenesis to
- Clinical Manifestations
- Laboratory investigation results
- Natural history of the disease
- Complications
Learning objective (Competency BI 1.1)
• Understand
the importance of various macromolecular
components of the cell and their functions
• Understandthe structure, function and inter-relationships
of biomolecules and consequences of deviation from
normal (biochemical aspects with few examples in
general)
Cell
• structural and functional unit of life
• basic unit of biological activity
Cell and subcellular organelles
Separated by differential ultracentrifugation
Based on density fractions form pellets and the
supernatant is formed
This supernatant has cytoplasm –
The marker enzyme is Lactate Dehydrogenase
Subcellular Pellet formed at centrifugal Marker enzyme
organelle force
Nucleus 600-750 x g (10 min)
Mitochondria 10000-15000 x g (10 min) Inner membrane: ATP synthase
Lysosome 18000-25000 x g (10 min) Cathepsin
Golgi complex 35000-40000 x g (30 min) Galactosyl
transferase
Microsomes 75000-100000 x g (100 min) Glucose 6-
phosphatase
Cytoplasm Supernatant Lactate
dehydrogenase
HOMEWORK ….
Functions of cell organelles
Differences between cytoplasm and cytosol
Lysosomes
tiny organelles; meant for degradation of : proteins, carbohydrates, lipids
and nucleotides
Lysosomal enzymes: hydrolyzing enzymes, optimum pH
around 5.
Polysaccharides hydrolyzing enzymes: Glucosidase, galactosidase,
mannosidase, hyaluronidase, sulfatase
Protein hydrolyzing enzymes- cathepsins, collagenase, elastase, peptidase
Lipid hydrolyzing enzymes - phospholipases
When membrane is disrupted, the released enzymes can hydrolyze external
substrates leading to tissue damage
1. Lysosomal storage diseases
Lysosomal enzymes are deficient leading to accumulation of lipids or
polysaccharides
2. Inclusion cell (I-cell) disease
Rare, lysosomes lack enzymes, but they are seen in blood
Mannose-6-phosphate is absent –This is a marker to target the nascent enzymes to
lysosomes
Enzymes can not reach their destinations-non entry of enzymes into lysosomes
Protein targeting defect
3. Cathepsins – Role in tumor metastasis
Cancer cells liberate the cathepsins out of the cells, which
degrade the basal lamina by hydrolyzing collagen and elastin,
so that other tumor cell can travel out to form metastasis
Marker enzyme - Cathepsins
4. Gout : when the urate crystals are
phagocytosed, cause physical damage to lysosomes, and release
of enzymes inflammation and arthritis result
Peroxisome
They contain peroxides and catalase, help in destroying
unwanted peroxides and other free radicals
• Insufficient oxidation of very long chain fatty acids by
peroxisomes- adrenoleukodystrophy (deficiency of peroxisomal
matrix proteins)
• Characterized by progressive degeneration of liver, kidney, brain
• Autosomal recessive condition
• In Zelweger syndrome, proteins are not transported to
peroxisomes
ECM – extra cellular
matrix
SLO
At the end of this lecture class student should know
1. What is extracellular matrix?
2. List the components of ECM
3. Functions
SLO 1- What is extra cellular matrix?
Cell and organs are surrounded by a glue like substance called ECM
Constitutes the non-cellular components of all tissues and organs
Mainly – supporting structure for the framework of the tissues
Actually plays – part – development, differentiation and maintenance of the tissues
and organs
SLO 2 - List the components of ECM
Water
Proteins
Polysaccharides
Proteoglycans
Fibrous proteins
Components of ECM are unique – function
ECM – highly dynamic structure – constantly being remodeled
SLO 3: Functions of ECM
Functional properties of ECM depends on the molecular compositions
Main
components
Proteoglycans Fibrous protein
The ECM is composed of an interlocking mesh of fibrous proteins and GAGs
Biochemical
and mechanical properties of each organ – dependent on
ECM composition
Post translational modifications undergone by ECM proteins are also
significant in their functions
Proteoglycans of ECM
Major protein
GAG chains linked to specific protein core
1. Leucine-rich proteoglycans – small molecules
2. Cell surface glycoproteins – act as core receptors – signal transduction
pathways involving growth factors + receptors
3. Modular glycoproteins – mediate cell adhesion migration and proliferation
The major proteins of ECM
Collagen
Elastin
Fibrillin
Fibronectin
Laminin
Collagen
To give support to organs
To provide alignment of cells – cell anchoring is possible
Proliferation and differentiation of cells
In blood vessels – collagen is exposed – platelet adhere –
thrombus formation
Elastin
ECF protein – recoil to tissues that undergo repeated stretching –
Elasticity
Major component of elastic fibers
Found in ligaments and Walls of the blood vessels
Fibrillin
Is a large glycoprotein which is essential for the formation of elastic fibres found
in connective tissue.
Is a component of myofibril
Found in eye lens, periostium of the bone and elastin fibres of aorta
Deficiency: Marfan syndrome
Fibronectin
A glycoprotein
Cell adhesion and migration
Clinical importance: Tumor cells that are deficient in fibronectin –
lack of adhesion – lead to metastasis
Laminin
Basal lamina of glomerular membrane
First Extracellular protein synthesized during embryogenesis
Involved in neuronal growth and nerve regeneration
Alzheimer’s disease
SLO covered???
Define ECM?
Components?
Functions?
Questions for SGT
Explain the structure of cell membrane
Explain the transport across the cell membrane
What is extracellular matrix? List the components of ECM
Functions of ECM
THANK YOU
