Saturday, April 18, 2020

Genetic Control of Protein Synthesis,
Cell Function, and Cell Reproduction

Gene:-
• Located in cell nucleus
• Control heredity from parents to children
• Control functions of cells by determining synthesis of substances, structures, enzymes & chemicals
• Composed of DNA
• Controls RNA formation which in turn controls protein synthesis

Gene Expression:-
The entire process from transcription of genes to translation of RNA and formation of proteins.
• 30,000 different genes form different proteins
• RNA (transcribed from same gene) is processed into different versions for alternate forms of a proteins
• 100,000 types of proteins are produced in body
• Proteins with other biomolecules form cellular organelles
• Some proteins are enzymes that catalyze chemical reactions & synthesize chemicals (Glycogen, ATP,etc).



》Genes Control Protein Synthesis
DNA:- A long double stranded helical molecule with end to end attached genes.

Building blocks of DNA:

(1) phosphoric acid
(2) a sugar (deoxyribose)
(3) four nitrogenous bases
(2 Purines=A-G & 2 Pyrimidines=T-C).

Phosphoric acid and Deoxyribose form two helical strands (backbone) and Bases (attached to Deoxyribose) lie b/w two strands and connect them.





Nucleotides:-
A single molecule of Phosphoric Acid, Deoxyribose and a base forms an acidic Nucleotide.
• 4 types depending on base
1) Deoxyguanylic
2) Deoxyadenylic
3) Deoxcytidylic
4) Deoxythymidylic




=> Nucleotides form DNA
• Form two DNA strands held together by weak cross linkages (Loose bonds or Hydrogen Bonds)
• Two strands can easily be pulled apart due to loose bonds
• Phosphoric acid and Deoxyribose form two helical strands (backbone) and Bases (attached to Deoxyribose) lie b/w two strands and connect them.
• Chargaff Rules:
1) Adenine bonds with Thymine
2) Guanine bonds with Cytosine
Simply=>Purines bond with Pyrimidines
A-T has two Hydrogen Bonds
G-C has three Hydrogen Bonds
• Ten pairs in each helix turn
=>Genetic Code (A code word):-
Genetic code enables DNA to control protein synthesis
• After splitting of strands bases appear and form genetic code
• Successive triplet of bases
• Control amino acid sequence in a protein
e.g. GGC, AGA, CTT (Separated by Arrows in the figure)


Each nucleotide is oppositely transcribed.
GGC, AGA, CTT
CCG, UCU, GAA



CCG codes for Proline,
UCU codes for Serine,
GAA codes for Glutamic Acid.


=》Transcription
Def: The process in which RNA is formed from DNA by code transfer.

• RNA from nucleus diffuses through nuclear pores into cytoplasm and controls protein synthesis
• The DNA in nucleus controls celluar functions in cytoplasm by RNA
=>Mechanism
• Synthesized in nucleus from DNA template
• DNA strands separate and one is used as a template
• Genetic Codes in DNA form codons (Complementary Genetic Codes) in RNA which control amino acid sequence in a protein
Basic Building Blocks of RNA.
Building blocks of RNA are similar to DNA except two things:-
RNA contains Ribose (with extra OH group) instead of Deoxyribose and Uracil instead of Thymine.

Formation of RNA Nucleotides.
The nucleotides containing bases Adenine, Guanine, Cytosine and Uracil instead of Thyamine are synthesized.

“Activation” of the RNA Nucleotides.
• Activated by RNA polymerase
• Two phosphates attach to right side nucleotides to form triphosphates with high energy phosphate bonds
• Energy becomes available for addition of new RNA nucleotides to RNA chain
Assembly of RNA Chain.
• Assembled by RNA polymerase
• RNA polymerase recognizes and attaches to promoter (Sequence of nucleotides ahead of gene to be transcribed).
• RNA polymerase unwinds and separates two turns of DNA helix
• RNA polymerase adds new activated RNA nucleotides to the RNA chain by following method
-> Forms a hydrogen bond b/w end base of DNA strand & base of RNA nucleotide in nucleoplasm
-> RNA polymerase breaks two of three phosphates in RNA nucleotides releasing energy for formation of covalent linkage b/w remaining phosphate of RNA nucleotide and end ribose of growing RNA chain.
-> RNA polymerase reaches chain-terminating sequence and separates RNA chain from DNA strand
-> DNA strands rebond and RNA chain is released into nucleoplasm
• Ribose and Deoxyribose bases combine in following manner



=> Types of RNA
Perform different functions
• Synthesize proteins
• Control gene regulatory functions
• Control post transcriptional RNA modifications
1. Precursor Messenger RNA (Pre-mRNA)
• Large & immature RNA
• Processed to form mature mRNA
• Contains two segments
i) Introns
->Removed by splicing

ii)Exons
->Retained in final mRNA

2. Small Nuclear RNA (snRNA)
• Directs splicing of Pre-mRNA to form mRNA
3. Messenger RNA (mRNA)
• Carries genetic code of a protein to cytoplasm
4. Transfer RNA (tRNA)
• Transports amino acids to ribosomes for protein assembly
5. Ribosomal RNA (rRNA)
• Forms 75 types of proteins
• Place of protein assembly
6. MicroRNA (miRNA)
• Consists of 21 to 23 nucleotides
• Regulates gene transcription & translation.
=》 Messenger RNA (The Codons)
• Single stranded & Suspended in cytoplasm
• Consist of hundred/thousand nucleotides
• Contains codons
e.g.
CCG codes for Proline,
UCU codes for Serine,
GAA codes for Glutamic Acid.

List of 22 Common Amino Acid (AA) Codons for Protein Synthesis
• Most AAs have more than 1 codons
• Single start codon for Chain Initiation
• Three stop codons for Chain Termination


=》 Transfer RNA (tRNA)
• Contains Anti-Codon
-> Triplet of nucleotide bases
-> Specific for a particular mRNA codon
(i,e; Anti-codon with GGG bases is specific for Codon with CCC bases)
-> Located below mid of molecule
• Plays essential role in protein synthesis because transfers amino acids to ribosomes
• 20 specific tRNAs exist for carrying 20 specific amino acids to ribosomes for protein synthesis .
• Recognizes specific mRNA codon in ribosomes and delivers amino acid at exact place of protein chain
• A small molecule with 80 nucleotides in a folded chain similar to cloverleaf.
• Amino acid attaches to OH group of ribose in adenylic acid.
• During Protein Synthesis
-> Anticodon bases combine with mRNA codon bases.
-> Amino acids line up one after another along mRNA chain establishing exact amino acid sequence in protein chain.



=》RIBOSOMAL RNA (rRNA)
• Ribosome
-> Composed of
> RNA (60%)
> Protein (40%)
- 75 types of protein
- Both structural proteins and enzymes
-> Physical manufacturing plant for protein synthesis
-> Functions with
> tRNA
- Transfers amino acids to ribosomes
> mRNA
- Provides information for sequencing amino acids in protein chain
-> Synthesis
> Occurs in nucleolus.
> rRNA synthesis genes are found in five chromosome pairs
> After synthesis rRNA collects in nucleolus
- Structure lying near chromosomes
- Size inc with inc. protein synthesis due to rRNA accumulation
- Processes rRNA by combining with ribosomal protein to form granular condensation products
_ Primordial ribosomal subunits
_ Move to cytoplasm by nuclear pores where assemble to form mature ribosomes.
_ Proteins form in cytoplasm not in nucleus because nucleus lacks mature ribosomes

=》Micro RNA (miRNA)
• Short (21 to 23 nucleotides) single-stranded RNA fragments
• Regulate gene expression
• Transcribed from DNA genes but not translated to proteins and are called non-coding RNA.
• Processed by cell into molecules complementary to mRNA that decrease gene expression
• Generation of miRNAs:-
-> Pri-miRNAs
> Longer primary precursor RNAs
> Primary gene transcripts
> Undergo processing in nucleus by microprocessor complex to pre-miRNAs
-> Pre-miRNAs
> 70-nucleotide stem-loop structures
> Undergo processing in cytoplasm by dicer enzyme to RISC (RNA-induced silencing complex) and miRNAs
• Function
-> Regulates gene expression by binding to complementary region of RNA and promoting repression of translation or degradation of mRNA before ribosomal translation.
-> miRNA alterations result in cancer and heart diseases


=》Small Interfering RNA (siRNA) (Synthetic miRNA / Silencing RNA / Short interfering RNA)
• A type of miRNA
• Short, double-stranded, 20-25 nucleotides
• Interfere with specific genes expression
• Administered to silence specific genes expression
• Avoids nuclear processing by microprocessor complex and enters cytoplasm where activates RISC silencing complex that blocks mRNA translation.
• Tailored for any specific gene sequence and block translation of any mRNA and repress expression by any gene for which nucleotide sequence is known.
• Researchers have proposed that siRNAs may become useful therapeutic tools to silence genes that contribute to pathophysiology of diseases.


=> Translation:-
• Protein formation process on ribosomes
• mRNA travels through ribosome beginning at “chain-initiating” (start) codon till "chain-terminating" (stop) codon.
• After start codon, ribosome reads amino acid codons and forms a specific protein then releases protein into cytoplasm after stop codon.
• Polyribosomes:
-> A cluster of 3-10 ribosomes attached at a time to an mRNA
-> mRNA
- Forms protein in several ribosomes at a time
- Initial end passes to successive ribosomes after leaving first.
- Has no specificity for ribosomes

• Ribosomes Attach to ER
-> Amino Acids in initial ends of forming protein attach to specific receptor sites on ER then enter ER matrix resulting in granular appearance during protein synthesis
-> Translation occurs in several ribosomes at a time in an mRNA.
-> Protein chains pass through ER membrane to ER matrix.
-> Except glandular cells which form protein-containing secretory vesicles while other cell ribosomes release proteins (Enzymes+Structural) in cytosol instead of ER

• Chemical Steps in Protein Synthesis
1. Each amino acid is activated by a chemical process in which ATP combines with amino acid to form an AMP complex with amino acid, giving up two high-energy phosphate bonds.

2. Activated amino acid combines with specific tRNA to form an amino acid-tRNA complex and releases AMP.

3. Amino acid-tRNA complex approaches mRNA molecule in ribosome. tRNA anticodon attaches to specific mRNA codon and lines up amino acid in appropriate sequence to form a protein molecule.

Peptidyl transferase (Ribosomal protein), forms peptide bonds between amino acids in protein chain. This requires two phosphate bonds making a total of 4 bonds used for each amino acid added to protein chain. So, protein synthesis is energy consuming.

• Peptide Linkage
OH is removed from COOH of one amino acid and H+ is removed from NH2 of other amino acid which combine to form water while remaining two reactive sites of C- and -N bond with each other to form peptide linkage.



=》 SYNTHESIS OF OTHER SUBSTANCES IN CELL
After synthesis, proteins (as enzymes) control almost all cellular reactions including synthesis of CLN that have other cell functions.

==》CONTROL OF GENE FUNCTION AND
BIOCHEMICAL ACTIVITY IN CELLS
• Genes control both physical and chemical functions of cells.
• Gene activation degree is controlled by at least one Internal Feedback Control otherwise cell parts overgrow and reactions over-act until cell death.
• Approx. 30,000 genes exist.
• Two methods of control for Cell Biochemical Activity:
-> (1) Genetic regulation:-
In which gene activation degree and gene product formation are controlled.
-> (2) Enzyme regulation:-
In which enzyme activity levels are controlled.

=》GENETIC REGULATION
( Regulation of gene expression)
"It is regulation of transcription in nucleus and translation in cytoplasm."
• Provides ability to respond to environmental changes
• Forms different types of cells, tissues, and organs (Differential Regulation)
• Allows different cell types to perform their specific functions.
• As cardiac myocyte contains same genetic code as renal tubular cell but genes expressed in cardiac myocyte are not expressed in renal tubular cell.
• Decides production and quantity of gene products (Proteins)
• Occurs at any point in transcription, RNA processing, and translation
• Promoter Controls Gene Expression.
-> Protein synthesis starts with transcription of DNA into RNA which is controlled by regulatory elements found in gene promoter


-> Basal promoter
> Found in protein-coding genes
> Binding site for RNA polymerase 2 that travels DNA to synthesize RNA
> Consists of seven bases (TATAAAA) called TATA box
- Binding site for TATA-binding protein, transcription factor IID complex and transcription factor IIB binds to both DNA and RNA polymerase 2

-> Upstream Promoter
> Located upstream from transcription start site
> Contains binding sites
- For +ve/-ve TFs that can affect transcription by interacting with basal promoter proteins
- Vary from gene to gene so give different gene expressions in different tissues.

-> Enhancers :-
> Affect transcription
> Bind TFs
> Located away from gene of action like
- On a different chromosome
- Upstream or downstream of gene
> Relatively close in coiled DNA
> 110,000 in human genome

-> Gene Separation:-
> Active genes (transcribing genes) from repressed genes.
> Difficult because of close occurrence of genes
> Achieved by chromosomal insulators

-> Insulators :-
> Gene sequences that provide a barrier to a gene against transcriptional influences from surrounding genes
> Vary in DNA sequences & binding proteins
> Modulated by DNA methylation
- e.g. Mammalian insulin-like growth factor 2 (IGF-2) gene.
- In which Mother’s allele has an insulator,
between enhancer and promoter, that allows binding of a transcriptional repressor.
- But, Paternal DNA sequence is methylated so transcriptional repressor cannot bind to insulator and IGF-2 gene is expressed from paternal copy of gene.



• Other Mechanisms of Promoter for Controlling Transcription
~ These are variations in basic mechanism of Promotor Control

1. Controlled by TFs located elsewhere in genome. Regulatory gene forms regulatory protein that acts either as an
activator or a repressor of transcription.

2. Different promoters are controlled at a time by a regulatory protein. At times regulatory protein acts as an activator for one promoter and as a repressor for another promoter.

3. Control can occur
-> At Start of transcription on DNA strand
-> At mid of transcription on DNA strand
-> During processing of RNA molecules in nucleus
-> During RNA translation by ribosomes

4.
-> In nucleated cells, nuclear DNA is packaged in specific structural units called chromosomes.
-> DNA within chromosome is wound around small proteins called histones, which are held tightly in a compacted state by some other proteins.
-> DNA cannot form RNA in compacted state.
-> Some control mechanisms decompact a portion at a time for partial RNA transcription.
-> Specific TFs control transcription rate by chromosomal promoters
-> Higher control orders establish proper cell function.
-> Outside cell signals (e.g. Hormones) activate specific chromosomal areas and specific TFs so control chemical machinery for cell function.

-> Large no. of genetic activity control is because of large no. of genes (30,000) in human cell.
-> Gene control systems control intracellular quantity of amino acids, amino acid derivatives, and intermediate substrates and products of carbohydrate, lipid, and protein metabolism.


=》CONTROL OF INTRACELLULAR FUNCTION BY ENZYME REGULATION
• Inhibitors or activators act on enzymes and control cell activities
• Second category of control mechanisms
• Enzyme Inhibition
-> Some substances (Inhibitors) inhibit specific enzyme systems that synthesize them.
-> Act on first enzyme in the sequence by binding on allosteric site and causing conformational change that inactivates enzyme
-> First enzyme inactivation prevents buildup of intermediary products
-> A negative feedback control
-> Controls quantities of amino acids, purines, pyrimidines, vitamins, and other substances

• Enzyme Activation
-> Inactive enzymes activate on demand
~ ATP Concentration
-> When ATP decreases in cell then breaks down into cAMP (Activator) that activates phosphorylase which splits glycogen into glucose that is metabolized and energy is used for ATP synthesis.
-> Thus, ATP conc. is regulated in cell

~ Purine and Pyrimidine Conc.
-> Purines and pyrimidines are needed in equal quantities for forming DNA and RNA
-> Purines form and inhibit their own enzymes but activate pyrimidine enzymes
-> Pyrimidines form and inhibit their own enzymes but activate purine enzymes
-> Thus, equal amounts of purine and pyrimidine form in cell

=》Summary
• Two principal control mechanisms for quantities of cellular constituents:
(1) Genetic regulation
-> Activates or inhibits genes
-> Feedback control system that monitors and corrects composition of cell
(2) Enzyme regulation
-> Activates or inhibits enzyme systems
-> Feedback control system that monitors and corrects composition of cell
• Hormones control by activating or inhibiting one or more intracellular control systems.


==》CELL REPRODUCTION
• Controlled by DNA–GENETIC SYSTEM
-> Determines growth & division of cells
-> Controls developmental stages of human from single cell fertilized ovum to whole functioning body
-> Central theme of life

=》Life Cycle of the Cell
• Period from one cell reproduction to next cell reproduction
• 10-30 hours in non-inhibited cells
• Terminated by Mitosis
-> Forms two daughter cells
-> 30 minutes
• Interphase
-> Interval between mitosis
-> 95 percent of life cycle
• Exceptional Conditions
-> Inhibitory factors slow or stop life cycle of cell so it varies from 10 hours (bone marrow cells) to entire life (nerve cells).

=》 Replication of DNA
• First step of cell reproduction in nucleus
• Duplication of DNA in chromosomes
• Followed by mitosis after 1-2 hour period of preliminary mitotic changes
• Starts 5-10 hours before mitosis while takes 4-8 in completion
• Forms two exact replicas of DNA that will be part of two daughter cells of mitosis
• Replication Events :-
Mostly same as RNA transcription except a few changes like
-> Both strands replicate instead of one
-> Entire strands replicate instead of small portions
-> Carried by DNA polymerase that attaches to and moves along DNA template strand while DNA ligase attaches new DNA nucleotides to one another by using high-energy phosphate bonds
-> DNA first forms in segments which then merge by DNA ligase
-> New strand remains attached to original strand and are coiled together.
-> Chromosome contains million DNA helixes each with 6cm length so cannot uncoil except for special mechanisms. Enzymes cut each helix, separate segment by rotation then resplice helix. Thus, two new helixes become
uncoiled.

• DNA “Proofreading” (DNA Repair)
-> 1 hour period between replication and mitosis
-> The process in which inappropriate DNA nucleotides are removed and replaced by appropriate complementary nucleotides with the help of DNA polymerases and DNA ligases is called DNA Proofreading.
• “Mutation” :-
-> Abnormality in transcription process.
-> Reduced by DNA Proofreading
-> Results in abnormal protein formation that leads to abnormal cell function and even cell death
-> 30,000 genes exist in human genome
-> Period between two human generations is 30 years in which 10 mutations can occur in passage of genome from parent to child
-> But protected by two chromosomal sets with identical genes so one functional gene is available to child despite mutations

• CHROMOSOME (AND THEIR REPLICATION)
-> Contains DNA helixes
-> 46 (23 Pairs) in human cell
-> Pair contains identical genes & may contain different genes
-> Contains histone proteins
> electropositively charged small & bobbin-like cores on which DNA helix coils
> Regulate DNA activity by tight packaging so DNA cannot form RNA or new DNA
> Regulatory proteins decondense histone packaging and allow RNA formation
-> Contains non-histone proteins
> Act as chromosomal structural proteins and as activators, inhibitors, and enzymes
-> Replication:-
> Occurs after a few minutes of DNA replication.
> New DNA helixes collect new protein molecules
> Two chromosomes (Chromatids) remain attached at centromere until mitosis

=》CELL MITOSIS
• The cell division in which two daughter cells with diploid number of chromosomes are formed
• Chromosomes replicate to form two chromatids followed by mitosis after 1-2 hours
• Mitotic Apparatus :-
-> Centrioles :-
> Two pairs lying close to each other near one pole of nucleus.
> Replicate before DNA replication
> Small cylindrical bodies with 0.4 ųm length & 0.15 ųm in diameter
> Consist of nine parallel tubules arranged as a cylinder
> In a pair lie at right angles to each other
> Centrosome = A pair of centrioles with Pericentriolar material
> Move apart due to growth of microtubule proteins between them called Spindle
> Some microtubules grow away from centriole pairs like a spiny star called Aster whose spines penetrate nuclear membrane and separate chromatids during mitosis
> Entire set of microtubules and two pairs of centrioles are called mitotic apparatus
• Prophase
-> First stage of mitosis
-> Spindles form
-> Chromosomes condense
• Prometaphase
-> Aster spines fragment nuclear membrane
-> Aster microtubules attach to chromatids at centromeres then in a later stage pull them to cellular poles
• Metaphase:-
-> Both aster microtubular spines push each other at mitotic spindle (where they interdigitate) by molecular motors.
> Minute contractile actin proteins extend between spines
> Slide spines in reverse direction
> So, by attached microtubules, pull chromatids to cell center that line up to form equatorial plate
• Anaphase:-
-> 46 pairs of chromatids are pulled apart that form separate sets of 46 chromosomes on each pole mitotic aster
• Telophase:-
-> Chromosome sets are completely pushed apart then mitotic apparatus dissolves
-> Nuclear membrane develops from ER
-> Contractile ring of microfilaments (actin & myosin) between two nuclei pinches cell into two daughter cells

=》CONTROL OF CELL GROWTH AND CELL REPRODUCTION
• Some cells grow and reproduce all time e.g.
(1) Blood-forming cells of bone marrow
(2) Germinal layers of skin
(3) Epithelium of gut
• Some cells may not reproduce for many years e.g. Smooth muscle cells
• Some cells do not reproduce during entire life of a person, except during fetal life. e.g. Neurons and striated muscle cells
• In some tissues, cells grow and reproduce after insufficiency like e.g.
-> After surgical removal of 7/8 of liver causes remaining 1/8 to grow into normal mass.
-> Glandular cells, bone marrow, subcutaneous tissue, intestinal epithelium except nerve and muscle cells.
• Cell number maintaining mechanisms are still poorly understood
• Three ways control growth
1)
• By growth factors that originate in adjacent tissues or other body parts & circulate in blood
e.g. Some gland epithelial cells (like pancreas) get growth factor from underlying Connective Tissue.

2)
• Insufficient space inhibits cell growth
e.g. Cells in a tissue culture grow until they contact a solid object then growth stops.

3)
• Cells in a tissue culture stop growing when their secretions collect in culture medium. It is a negative feedback control
• Telomeres
-> A region of repetitive nucleotide sequences located at each end of a chromatid
-> Protective caps that prevent chromosomal degradation during cell division
-> Disposable chromosomal buffer
-> “Primer” RNA does not attach to very end of DNA and starts replication after missing a small DNA part so copied DNA loses additional nucleotides from telomere region without which genomes lose information after each cell division.
-> 8000 base pairs at birth to 1500 base pairs in old age in blood cells
-> Lose 30-200 base pairs/cell division
-> Shorten to a critical length, chromosomes become unstable and cells die
-> Add to physiological changes of aging.
-> May erode because of oxidative stress and inflammatory diseases
-> Get additional bases by Telomerase in some cells like stem cells of bone marrow & skin, germ cells of ovaries and testes.
-> Cells with low telomerase activity inherit defective chromosomes, become senescent (old) and cease dividing.
-> Regulate cell proliferation and maintain gene stability
-> Cancer cells have high telomerase activity that maintains telomere length even after uncontrollable proliferation
-> Shortening protects from cancer and other proliferative diseases

• Regulation of Cell Size
-> Determined by amount of DNA in nucleus
-> If no replication occurs, size will be normal & constant
-> Chemical Colchicine prevents mitotic spindle formation and mitosis despite continued DNA replication
-> So, DNA quantity rises which forms more RNA that forms more protein, ultimately cell grows larger.

==》CELL DIFFERENTIATION
• Property of cell growth and cell division
• "Changes in physical and functional properties of cells as they proliferate in embryo to form different bodily structures and organs"
• Experiment
-> When nucleus from an intestinal mucosal cell of a frog is surgically implanted into a frog ovum from which original ovum nucleus was removed, result is formation of a normal frog.
-> So a differentiated cell carries all genetic information for development
• Occurs due to selective repression of different gene promoters
• Some DNA helix portions wound around histone cores condense and no longer uncoil to form RNA molecules
• Cellular genome produces a regulatory protein that forever represses a select group of genes
• Mature human cells produce less proteins (8000-10,000) than total number of genes (30,000) in cell.
• In embryo adjacent cells control differentiation e.g.
-> Primordial chorda-mesoderm
(Primary Organizer)
> Forms a focus for embryo development
> Differentiates into a mesodermal axis that contains somites and forms body organs due to adjacent tissue inductions
-> Eye vesicles (Induction)
>Approach head ectoderm
>Thicken ectoderm into lense plate that folds inward to form eye lense

==》APOPTOSIS
• "Programmed (suicidal) cell death"
• Body contains 100 trillion cells (organized community) regulated by rate of cell division and cell death otherwise tissues shrink or grow excessively
• When cells become useless or threat to organism then undergo apoptosis.
• Cells do not spill contents so adjacent cells remain healthy
• Occurs in tissues that remodel during development
• In intestine and bone marrow billions of cells die each hour and replaced by new cells
• Mechanism:
Apoptosis initiates when procaspases activate into caspases (proteases) that cleave and activate other procaspases which triggers a proteolytic cascade that condenses cell by disassembling cytoskeleton and alters cell surface so macrophage attaches and digests cell
• Abnormalities result in neurodegenerative diseases (Alzheimer disease), cancer and autoimmune disorders
• Induced in cancer cells by some drugs

==》Necrosis
• Injured cell death due to swelling and bursting of fragile membrane
• Cells spill contents that inflame & injure adjacent cells

==》CANCER
• Due to mutation or abnormal activation of genes that control cell growth and mitosis.
• Proto-oncogenes:-
-> Normal genes
-> Control cell adhesion, growth, and vision
-> After mutation or excess activation become oncogenes that
> Function abnormally
> Cause cancer
> 100 types
• Tumor Suppressor Genes
(Anti-Oncogenes)
-> Suppress activation of specific oncogenes
-> Loss or inactivation activates oncogenes that lead to cancer
• Fewer cells become cancerous after mutation because (Factors decreasing cancer chances)
1)
Most Mutated cells die

2)
Few survived mutated cells become cancerous because of feedback control

3)
-> Cancerous cells are destroyed by immune system.
-> Mutated cells form abnormal proteins (because of abnormal genes) that stimulate immune system for formation of antibody or lymphocytes that react and destroy cancerous cells.
-> Suppressing immune system by taking drugs after kidney or heart transplantation increases cancer chances by fivefold.

4)
-> Different oncogenes at a time cause cancer
e.g. A gene promoting rapid production of a cell will not produce cancer because a gene for blood vessel formation is absent at the same time.






=》Organization of Cell
• Contains two parts
i) Nucleus: Separated from cytoplasm by nuclear membrane
ii) Cytoplasm: Separated from surrounding fluid by plasma membrane
• Protoplasm:- Substances that make up cell..
e.g. i) Water, ii) Electrolytes, iii) Lipids, iv) Proteins, v) Carbohydrates

1)=> Water
• Principal fluid medium of cell
• Present in most cells except Fat Cells
• 70-85% of cell
• Contains dissolved chemicals (take part in reactions) & suspended particles (places of reactions)

2)=> Ions
• Inorganic chemicals for cellular reactions
• Necessary for cellular control mechanisms
e.g. Transmit impulses in nerves and muscle fibers

3)=> Proteins
• Abundant in cell after water
• 10-20% of cell
• Two types
• i) Structural Proteins
->Long filaments & polymers
->Form microtubules, which provide cytoskeleton of
-Cilia
-Nerve Axons
-Mitotic Spindles (Cell Division)
-Tangled Mass (holding cytoplasm & nucleoplasm in their compartments)
->Fibrillar Proteins
-Found outside cell as collagen & elastin of blood vessel wall, tendon, ligaments,etc.
• ii) Functional Proteins
-> Tubular-globular
-> Mainly enzymes
-> Often mobile
-> Adherent to membranous structures
-> Come in contact with substances & catalyze
-> Split glucose into its constituents
-> Provide energy for cellular functions

4)=> Lipids
• Heterogenous group of compounds
• Soluble in fat solvents
• Phospholipids & Cholestrol
-> 2% of total cell mass
-> Due to water insolubility form membranes
• Triglycerides
-> Neutral fats
-> 95% of fat cells (store-house of energy giving nutrients)

=> Carbohydrates
• Minor structural function (Glycoprotein) but major nutritive function (Glucose).
• %age
-> Average cell (1% of total mass)
-> Muscle cell (3% of total mass)
-> Liver cell (6% of total mass)
• Readily available in ECF as Glucose
• Stored as Glycogen in cells
-> A glucose polymer
-> Depolymerizes when needed for energy

PHYSICAL STRUCTURE OF THE CELL
=> Introduction
• Organelles
-> Organized physical structures
-> Important to cell as Mitochondrial absence results in cessation of 95% of cell's energy releasing from nutrients.

=> MEMBRANES OF CELL
• Composed mainly of Lipid & Proteins
• Include membranes of
-> Cell
-> Nucleus
-> Endoplasmic Reticulum
-> Mitochondria
-> Lysosomes
-> Golgi apparatus.
• Lipid
-> Prevents passage of water & water-soluble substances

• Proteins (Penetrating Membrane)
-> Pathways/Pores for passage of specific substances
-> Catalyse (enzyme) chemical reactions

=> Cell Membrane (Plasma Membrane)
• Envelops cell
• Thin, pliable & elastic
• 7.5-10nm thick
• Composed mainly of Lipid & Proteins
• Composition
-> Proteins 55%
-> Phospholipids 25%
-> Cholesterol 13%
-> Other lipids 4%
-> Carbohydrates 3%

• Lipid Barrier
->Lipid bilayer
>Two layered lipid film
>Each layer = 1 molecule thick
>Continuous on cell surface
>Large globular proteins interdigitate
->Composed of
1) Phospholipids
> Abundant lipids
>Two ends
- Hydrophilic end
_Water soluble
_Fat insoluble
_Phosphate portion
_Constitute two surfaces, one faces intracellular water and other faces extracellular water.
- Hydrophobic end
_Water insoluble
_Fat soluble
_Fatty acid portion
_Repelled by water but attracted to each other in middle of membrane
_Impermeable to water-soluble substances, such as ions, glucose, and urea.
_Permeable to fat-soluble substances, such as oxygen, carbon dioxide, and alcohol.

2) Sphingolipids
> Derived from amino alcohol sphingosine
> Have hydrophobic and hydrophilic groups
> Found in less quantity especially in nerve cell membranes
> Functions
-Protection from harmful environmental factors
-Signal transmission
-Adhesion sites for extracellular proteins

3) Cholesterol
> Contains fat soluble steroid nuclei
> Dissolved in bilayer
> Determines degree of permeability (Or Impermeablility) of water-soluble substances
> Controls fluidity of membrane

• Proteins (of Membrane)
-> Globular masses floating in lipid bilayer
-> Mainly glycoproteins
-> Two types
1) Integral Proteins
> Protrude all way through membrane
> Act as structural channels (or pores)
-Through which water and water-soluble substances (e.g.ions) diffuse
-Allow selective diffusion
>Act as carrier proteins
- Transport substances (Which don't otherwise/in any other way cross lipid bilayer)
- Transport substances opposite to their diffusing gradients (Active Transport)
> Act as Enzymes
> Act as Receptors
- For water-soluble chemicals like peptide hormones
- Ligands bind to receptor causing conformational changes in receptor. This induces interactions between receptor and cytoplasmic proteins (second messengers) that transmit signals from cell's exterior to interior.
2) Peripheral Proteins
> Attached to integral proteins on one surface of membrane
> Act as enzymes or transport controllers

• Carbohydrates (of Membrane)
-> Exist as glycoproteins (with most of integral proteins) or glycolipids (with 1/10 of Lipids) or Proteoglycan's (CHO+Protein Core). Glyco portions protrude outside and swing loosely.
-> Outside surface of cell with a loose carbohydrate coat is called glycocalyx.
-> Functions
1. Have -ve charge & repel other -vely charged substances
2. Attach cells to one another
3. Act as receptors for binding hormones,
(e.g. Insulin).
- Binding activates internal proteins that activate intracellular enzaymes
- Some carbohydrate moieties enter into immune reactions


=> CYTOPLASM AND ITS ORGANELLES
• Contains minute and large particles, and organelles
• Contains
-> Neutral Fat Globules, Glycogen granules, Ribosomes, Secretory Vesicles.
-> Five important organelles; Endoplasmic reticulum, Golgi apparatus, Mitochondria
• Cytosol
-> Jelly-like fluid portion of cytoplasm with dispersed particles
-> Contains dissolved proteins,
electrolytes, and glucose.

• Endoplasmic Reticulum
-> Network of tubular and flat vesicular
structures
-> Processes molecules made by cell and transports them to their specific destinations inside or outside cell.
-> Tubules and vesicles
> Interconnected
> Their walls' composition resembles cell membrane but 30-40 times greater in total surface in liver cells.
> Their inner space
- contains endoplasmic matrix, a watery medium, and continuous with space between two layers of nuclear membrane.
- Allows entry of cellular chemicals and directs them to specific areas
> Attached enzyme systems provide machinery for metabolic cellular functions
-> Granular Endoplasmic Reticulum
> Ribosomes
- Minute granular particles attached to outer surfaces
- Composed of RNA and proteins
- Involved in protein synthesis
> ER with Ribosomes is termed as GER.
-> Agranular Endoplasmic Reticulum
> ER without Ribosomes is termed as AER.
> Involved in synthesis of lipids and in processes promoted by intrareticular enzymes

• Golgi Apparatus
-> Closely related to ER
-> Membrane resembles AER
-> Four or more stacked layers of thin, flat, enclosed vesicles lying near one side of nucleus.
-> Prominent in secretory cells and located on their secretory portion.
-> ER vesicles continually pinch off
from ER then release substances by fusing with Golgi apparatus.
-> Substances are processed to form lysosomes, secretory vesicles, and other
cytoplasmic components.

• Lysosomes
-> Vesicular organelles
-> Form by breaking off from Golgi Apparatus then disperse in cytoplasm.
-> Provide an intracellular digestive system that digests
(1) Damaged cellular structures
(2) Ingested food particles
(3) Unwanted matter such as bacteria
-> 250-750 nm in diameter (nm D)
-> Surrounded by lipid bilayer membrane
-> Contains small granules (5-8nm D) having 40 different hydrolase (digestive) enzymes.
-> Hydrolytic Enzymes
> Split organic molecules into two or more parts by combining H and OH portions of H2O with different parts of a compound. e.g.
- Protein --------》Amino acids
- Glycogen --------》 Glucose
- Lipids --------》 Fatty acids & Glycerol.
> Concentrated in Lysosomes and prevented by membrane from digesting cellular structures.
> When membrane breaks then come in contact with organic substances and split them to small & diffusable parts like Glucose and Amino Acids

• Peroxisomes
-> Physically resemble lysosomes but different in two ways:
1) Formed by self replication or by budding from AER (SER) not Golgi Apparatus
2) Contain Oxidases not Hydrolases
-> Oxidases combine O2 with H ions to form H2O2 (An oxidizing substance) used with Catalase (An oxidizing enzyme).
- Oxidize substances that might be poisonous to cell
-> Half of drunk alcohol is detoxified into acetaldehyde by peroxisomes of liver cells
-> Catabolize long chain fatty acids
• Secretory Vesicles
-> Involved in secretion of substances
-> Formed by ER-Golgi apparatus system then released into cytoplasm from Golgi Apparatus as storage vesicles (Secretory Vesicles / Secretory Granules).
-> Store proenzymes (Inactivated enzymes) in pancreatic acinar cells.
> Secreted by outer cell membrane into pancreatic duct then into duodenum then become activated and digest food.

• Mitochondria
-> Extract energy from nutrients for cellular functions, so termed as Powerhouses of cell.
-> Number varies from less than a hundred to several thousand as per cell physiology e.g.
Cardiomyocytes > Adipocytes
-> Located in active portions of cell
-> Variable in size and shape e.g.
From few hundred nm D & globular to 1 ųm D & 7 ųm length
-> Composed of two lipid bilayer membranes
1) Outer membrane
2) Inner membrane
-> Cristae
> Tubular structures formed by infoldings of inner membrane
> Sites
- For attachement of oxidative enzymes
- For occurrence of chemical reactions
-> Matrix
> Occupies inner cavity of mitochondrion.
> Contains enzymes that extract energy from nutrients.
-> Cristae and Matrix enzymes together cause oxidation of nutrients by forming CO2+H2O and releasing energy. This energy is used to form ATP. ATP diffuses through out cell and releases energy for cellular functions.
-> Self-replicative i,e; one can form another as per ATP need (as per cell physiology). Because of presence of DNA.


• Cell Cytoskeleton
-> Network of fibrillar proteins organized into filaments or tubules
-> Ribosomes synthesize precursor proteins that polymerize to form filaments. e.g.
~ Ectoplasm
> Actin filaments in outer zone of cytoplasm
> Elastic support for cell membrane

~ Muscle Contractile Machine
> Formed by actin & myosin organization
> Cause muscle contraction

~ Microtubules.
> Composed of polymerized tubulin
> Strong filaments
> Found in flagellum of sperm, center of cilium, centrioles and mitotic spindle.
-> Functions
> Provides rigid physical structures for cell
> Determines cell shape & participates in cell division
> Allows cells to move
> Provides a track for movement of organelles within cell

• Nucleus
-> Controls center of cell
-> Sends messages to cell to grow and mature, to replicate, or to die
-> Contains DNA, comprising of genes.
-> Genes
> Determine characteristics of proteins like structural proteins and enzymes that
control cytoplasmic and nuclear activities.
> Control and promote reproduction of cell
> Mechanism
- Firstly two identical genes are formed. Mitosis forms two daughter cells each of which carries one set of DNA genes.
-> Chromatin Material
> Darkly staining during interphase
> Organized into Chromosomes during mitosis
-> Nuclear Membrane (Nuclear Envelope)
> Composed of two lipid bilayer membranes
1) Outer membrane
- continuous with outer membrane of ER
2) Inner membrane
> The space b/w nuclear membranes is continuous with space b/w ER membranes.
> Contains thousands of nuclear pores
- Protein substances attach to pores and decrease diameter to 9nm.
- Molecules of 44,000 MW can pass

-> Nucleoli
> Staining structures in nuclei of cells
> Lacks a membrane
> Contain RNA & ribosomal proteins
> Enlarge during protein synthesis
> Form within nucleus whereas Ribosomes form within cytoplasm
> DNA genes synthesize RNA, some of which are stored in nucleoli but mostly transported to cytoplasm
> Here along with specific proteins assemble mature Ribosomes for forming cytoplasmic proteins.


=> COMPARISON OF ANIMAL CELL
WITH PRECELLULAR FORMS OF LIFE
• It is believed that animal cell has evolved (Million years back) from a virus like simple organism.
-> 15 nm: Small virus
-> 150 nm: Large virus
-> 350 nm: Rickettsia
-> 1 µm: Bacterium
-> 5-10 µm+: Cell
• (1) Small Virus
-> 15 nm
-> Nucleic acid
> Embedded in protein coat
> Composed of DNA & RNA
> Self-Replicative
> Makes virus a living structure by propagating its lineage.
• (2) a Large Virus
-> 150 nm
• (3) a Rickettsia
-> 350 nm
• (4) a Bacterium
-> 1 µm
• (5) a Nucleated Cell
-> 5-10 µm+
-> 1000 times diameter of small virus
-> 1 Billion times volume of small virus
• Evolution of Life
~ As life evolved
-> More chemicals and specialized functions developed
-> Formation of membrane with a fluid matrix
-> Specialized chemicals developed
-> Enzymes appearance with catalysis
-> Organelles developed
> Rickettsial and Bacterial stages
> More efficient than dispersed chemicals
-> Complex organelles developed
> Nucleated cell stage
> Like Nucleus
- Distinguishes animal cell from lower forms of life
- Control center for cellular activities
- Provides reproduction of new cells


=> FUNCTIONAL SYSTEMS OF THE CELL
• ENDOCYTOSIS
~ "INGESTION BY CELL"
~ "Large particles enter cell by specialized function of cell membrane"

-> The life, growth and reproduction of cell need nutrients that pass membrane by diffusion or active transport.
-> Diffusion
> "Movement of molecules from area of high conc. to area of low conc. due to random molecular motion."
> Through Channels/Pores (Water-soluble Substances )
> Through Lipid matrix (Fat-soluble Substances)
-> Active Transport
> Carrying of a substance through membrane by carrier type of integral proteins (that protrudes all the way through membrane).
~/-> Two forms of Endocytosis

1) Pinocytosis (Cell Drinking)
> Ingestion of minute particles
> Vesicles of extracellular fluid
> Occurs continually
> Occurs in most cells but rapid in some cells e.g.
-In macrophages 3% of membrane is engulfed as vesicles/minute
> Small vesicles
- 100-200nm D
- Seen only by EM
> Pinocytosis = Macromolecule Attachment
> Way of entry of large protein molecules
> Mechanism:
- Specific protein molecules attach to specific receptors (specialized proteins) in small pits (coated pits) on membrane.
- Inside of pits contains Clathrin (Fibrillar Protein), Actin and Myosin (Contractile Protein Filaments).
- After binding of protein molecules with receptors, pit invaginates with fibrillar proteins closing the borders over attached proteins and small ECF fluid.
- Invaginated portion breaks away and forms pinocytotic vesicle.
- Exact cause of formation is not yet clear.
- Energy is supplied by ATP
- Calcium ions of ECF react with Contractile Protein Filaments that provide force for pinching the vesicle.

2) Phagocytosis (Cell Eating)
> Ingestion of large particles (Like bacteria, cells, or portions of degenerating tissue)
> Occurs in same way as pinocytosis except involving large particles than molecules
> Occurs in few cells like Macrophages and WBCs
> Initiates due to binding of a bacterium, dead cell or tissue debris on surface receptors of phagocyte
In case of a bacterium binding occurs between phagocyte receptors and antibody already attached to bacterium for purpose of dragging it to phagocyte receptors ( Termed as Opsonization).
> Mechanism:
- Membrane receptors attach to surface ligands of particle.
- Membrane evaginates around particle with receptors attaching to more surface ligands of particle then closed phagocytic vesicle is formed
- Contractile fibrils contract around outer edge of phagocytic vesicle then pinch and push vesicle to cell interior.

• Lysosomes Digest Endocytosed Foreign Particle
-> Digestive Vesicle
> (Digestive organs of cell)
> Lysosomes attach to endocytosed vesicle and release acid hydrolases forming a Digestive Vesicle.
> Hydrolyses CPLN into AA, FA and Glucose that diffuse into cytoplasm
> Residual Body
- Digestive vesicle with indigestible substances.
- Excreted by cell through exocytosis

-> Regression of Tissue
> Process of reduction of tissue mass
e.g.
- In uterus after pregnancy
- In muscles during long periods of inactivity
- In mammary glands at end of lactation
> Due to lysosomal activity

-> Autolysis of Cell
> Lysosomes remove
- Damaged cell
- Damaged portions of cell
> Cell damage (due to heat, cold, trauma & chemicals) ruptures lysosomes
> Hydrolases digest organic substances
> In slight damage cell portion is removed and repaired
> In severe damage whole cell is removed (Autolysis) and replaced by new cell formed by mitotic division of adjacent cell.

-> Lysosomes Bactericidal Action
> Contain bactericidal agents that kill phagocytized bacteria
> Two types of agents
1) Lysozyme :-
- Dissolves bacterial cell membrane.
2) Lysoferrin :-
- Binds iron and other substances before they can promote bacterial growth.
3) Acid with 5.0 pH
- Activates hydrolases and inactivates bacterial metabolic systems

-> Autophagy
> "Recycling of Cell Organelles"
> Literally means, “to eat oneself.”
> Process in which obsolete organelles and proteins degrade and recycle
> Autophagosomes
- Transfer worn-out cell organelles to lysosomes
- Double membrane structures
- Formed in cytosol
> Mechanism:-
Lysosomal membrane invaginates and forms vesicles for taking organelles into lysosomal lumen where get digested and nutrients are reused.
> Importance:-
- Contributes to routine turnover of cytoplasmic components
- Develops tissue and gives survival to cells during nutrient scarce conditions
- Maintains homeostasis
- In liver cells, Mitochondrion has life span of 10 days

=> Functions of Endoplasmic Reticulum
• Contains lipid bilayer membrane with protein enzymes that catalyze substance synthesis
• Synthesis begins in ER then products pass to Golgi apparatus where undergo processing and release into cytoplasm
• GER forms proteins
-> Contains ribosomes on outer surface
-> Ribosomes synthesize protein molecules and extrude them to cytosol and endoplasmic matrix.
• SER forms lipids
-> Synthesizes lipids like Phospholipids and Cholesterols which incorporate into & extend lipid bilayer of ER
-> ER growth remains in limit by continuous breaking of vesicles
• Other Functions of ER (Mostly of SER)
1. It provides enzymes that control glycogen breakdown when glycogen is used for energy.
2. It provides enzymes that detoxify drugs by coagulation, oxidation, hydrolysis, and conjugation with glycuronic acid.

=> Functions of Golgi Apparatus
• Synthesizes carbohydrate polymers not synthesized by ER like Hyaluronic acid and Chondroitin sulfate which are Involved in migration and proliferation of cells and are major components of:
-> Proteoglycans secreted in mucus and other glandular secretions
-> Ground substance, acting as fillers between collagen fibers and cells
-> Organic matrix in both cartilage and bone
• Processing and Vesicle Formation :-
-> Major function of ER and Golgi Apparatus
-> Substances (e.g. Proteins) form in GER then move to SER where pinch off to form vesicles that diffuse into deepest layer of Golgi apparatus and release substances.
-> Substances
> Receive carbohydrate moieties
> Compact into highly concentrated packets
> Pass to outer layers undergoing compaction and processing
> Finally pinch off as Golgi vesicles and diffuse throughout cell
-> Timing of these processes :-
> A glandular cell is bathed in
radioactive amino acids
> Radioactive protein molecules are detected in
- GER within 3-5 min.
- Golgi apparatus within 20 min
- Cell surface secretions within 1-2 hours

• Types of Vesicles :-
-> 2-types
1) Secretory Vesicles
2) Lysosomes
-> Some vesicles are destined for intracellular use.
-> In secretory cells, Golgi apparatus mainly forms secretory vesicles.
> First diffuse to cell membrane
> Then after calcium ions interaction, fuse with cell membrane and release substances to exterior by exocytosis
- Opening of membrane's outer surface for extrusion of contents

( Way of calcium ions interaction with vesicular membrane to cause fusion is not yet known.)
• Intracellular Vesicles Replenish Cellular Membranes
-> Golgi vesicles fuse with cell and organelles' membranes like mitochondria, ER, and extend them. Thus, replenish them as they're used in endocytotic vesicles.
-> So, Golgi apparatus and ER form intracellular structures and secretory substances.

=> MITOCHONDRIA
(EXTRACT ENERGY FROM NUTRIENTS)

• Cells extract energy from foodstuffs (like Glucose, AA, FA) after reacting with oxygen
• GIT and Liver convert organic nutrients into their monomers before undergoing cellular metabolism e.g.
-> Carbohydrates ----> Glucose
-> Proteins ----> Amino Acids (AA)
-> Fats/Lipids ----> Fatty Acids (FA)
• Mechanism:-
-> Foodstuffs
> Enter cell
> React with oxygen
-> Enzymes control reaction and channel released energy in proper direction
-> Reactions occur in mitochondria
-> Released energy is used to form ATP
-> ATP is used to energize intracellular metabolic reactions.

=> Functional Characteristics of ATP
• A nucleotide
• Composed of
1) Nitrogenous base adenine
2) Pentose sugar ribose
3) Three phosphate radicals
• Last two phosphate radicals are connected by high energy phosphate bonds
-> Represented by ~
-> Contain 12,000 cal./mole of ATP
-> Very labile and splits instantly on demand
• Mechanism:-
-> ATP releases energy by splitting into phosphate radical (Pi) and ADP
-> Released energy is used to energize cellular functions like synthesis of substances and muscular contraction.
-> Phosphate radical (Pi) and ADP gain energy from cellular nutrients by recombining into ATP
-> And Entire process is repeated
-> So, ATP is energy currency of cell because it can be spent and remade continually with turnover of few minutes.

=> Chemical Processes in Formation of ATP (Role of Mitochondria)

• After entering cell, Glucose is converted into Pyruvic Acid through Glycolysis
-> Few ADP convert to ATP
-> 5% of cell energy metabolism
-> 95% of ATP forms in Mitochondria

• Pyruvic acid (from carbohydrates), fatty acids (from lipids), and amino acids (from proteins) convert into acetyl-coenzyme A (CoA) in mitochondrial matrix.
-> Undergoes dissolution through Citric Acid Cycle (Krebs Cycle) for extracting energy.
> acetyl-CoA splits into H atoms and CO2
> CO2 diffuses out of mitochondria then out of cell and finally excreted through lungs
> H atom combines with oxygen giving tremendous release of energy that forms ATP
Mechanism
- Protein enzymes (ATP Synthetase) are integral part of cristae that protrude into mitochondrial matrix
- Firstly an electeon is removed from H atom, converting it into hydrogen ion
- Lastly hydrogen ions combine with oxygen to form water+tremendous release of energy to ATP synthetase. Which uses energy to form ATP from ADP.
- ATP is transported out of mitochondria into cell cytoplasm and nucleoplasm, where energizes cell function.
- This whole process is called chemiosmosis (ATP formation).

• Uses of ATP in Cellular Function
~ATP is used mainly in three functions
(1) Transport e.g.
-> Na, K, Other ions and organic substances transport through membrane
-> Accounts for 80% of ATP in renal tubular cells

(2) Synthesis e.g.
-> Protein ( by ribosomes), Phospholipids, cholesterol, purines, pyrimidines, etc.
-> Protein is composed of amino acids linked by peptide linkages. One such linkage requires breakdown of 4 high energy bonds.
-> Accounts for 75% of energy in some cells especially during growth phase.

(3) Mechanical work e.g.
-> Muscle contraction, ciliary and ameboid motion.
• ATP in a Nut Shell (Summary)
-> Always available to release energy rapidly when needed
-> Alternative chemical reactions are slower
-> Formed by breakdown of CPLN
-> More than 95% is formed by Mitochondria so termed as PowerHouses of Cell

=> LOCOMOTION OF CELLS
• Muscle cells constitute 50% of body mass and have most obvious movement.
• Two other movements include
-> Ameboid Locomotion
-> Ciliary Movement
• AMEBOID MOVEMENT
-> Cell movement in relation to surroundings e.g. WBCs movement through tissues.
-> Resembles amebae movement
-> Pseudopodium
> Protrudes from one end
> Projects away from cell body & secures new tissue area
> Now cell remainder is pulled to pseudopodium
-> Mechanism
> At leading edge of pseudopodium new membrane is formed continuously by fusion of exocytotic vesicles
> In mid and rear portions of cell old membrane is absorbed continuously by formation of endocytotic vesicles
> Exocytotic vesicles are lined by receptors proteins. After fusion, Proteins attach to ligands in surrounding tissue and pull cell remainder to pseudopodium.
> At opposite end of cell, receptors pull away from ligands and form new endocytotic vesicles which move to pseudopodial end and form new membrane for pseudopodium
> Ameboid cells contain an actin protein in cytoplasm. Actin polymerizes to form filamentous network in enlarging pseudopodium and contracts after binding to myosin by utilizing ATP.
> Contraction also occurs in ectoplasm of cell body due to presence of an actin network.

-> Types of Cells exhibiting ameboid locomotion
> When WBCs move from blood to tissues to form macrophages
> Fibroblasts move to damaged area for repairing.
> Germinal cells of skin, ordinarily sessile, move to cut area for repairing the opening
> Embryonic cells move long distances from origin sites to new areas


-> Control of Ameboid Locomotion
(Chemotaxis)

> Chemotaxis:-
"The process which initiates ameboid locomotion due to appearance of chemical substances in tissues is called Chemotaxis."
> Chemotactic Substance:-
"The chemical causing chemotaxis is called chemotactic substance."
> Positive Chemotaxis:-
- When movement occurs towards source of chemotactic substance.
- Towards chemical gradient
> Negative Chemotaxis:-
- When movement occurs away from source of chemotactic substance.
- Away from chemical gradient
> Exact mechanism of control by chemotaxis is not yet known:-
- However, known facts elaborate that Cell side exposed to chemotactic substance develops membrane changes that cause pseudopodial protrusion.


=> CILIA AND CILIARY MOVEMENTS
• Whip like cilia movement on cell surface
• Occurs in two places
1) On surfaces of respiratory airways
2) On inside surfaces of uterine tubes
• In nasal cavity and lower respiratory airways moves mucus layer at 1 cm/min toward pharynx for removing trapped particles
• In uterine tube, moves fluid from uterine tube ostium to uterus cavity for transporting ovum
• Cilium
-> Sharply pointed straight or curve hair projecting 2-4 ųm from cell surface.
-> Many cilia project from a single cell
e.g. 200 cilia on epithelial cell in respiratory airway.
-> Covered by cell membrane protrusion
-> Supported by
- 11 microtubules & 9 double tubules around periphery of cilium
- 2 single tubules in center
-> An outgrowth of its basal body that lies beneath cell membrane
-> Moves forward with a sudden bending at cell surface (Rapid whiplike stroke 10 to 20 times per second.).
-> Then moves backward slowly to initial position.
-> Rapid forward-thrusting pushes fluid
in forward direction
-> Slow backward movement has almost no effect on fluid movement.
-> Fluid continually propels in fast stroke direction. Because cells have many cilia with same direction.
• Sperm Flagellum
~ Mostly similar to cilium except
-> Longer and moves in quasi-sinusoidal waves instead of whiplike movements

• Mechanism of Ciliary Movement:-
(All aspects of ciliary movement are not known)
1]-> Nine double tubules and two single tubules are linked by protein cross-linkages; collectively called axoneme.
2]-> Cilium can beat even when membrane+other elements, exceptp axoneme, are removed.
3]-> Two conditions for axoneme continued beating after removal of other elements
i) ATP
ii) Appropriate ionic conditions like Mg & Ca
4]-> During forward stroke, front edge double tubules slide outward to cilium tip
while those on back edge remain in place
5]-> Multiple protein arms composed of protein dynein (ATPase) project from each double tubule toward an adjacent double tubule
-> ATP releases energy to ATPase dynein arms causing their heads to crawl along adjacent double tubule.
-> Front tubules crawl outward while back tubules remain stationary and result in bending.
Cilia contraction control is not understood
->Cilia without central tubules fail to beat. So, A signal might be transmitted along these to activate dynein arms.


Wednesday, August 21, 2019

One has to endure a series of continuous nerve wracking circumstances in order to approach the destined summit of the life.


The field of medicine is hopefully vast enough to be regarded as being out of one's precise grip, so it would be better to make some outlines for it.

Friday, August 16, 2019

The entry into the medical school is for sure a dream that has just come true for all the lucky students out there. On such an amazing occasion one's mind is filled with great joy & happiness.


With the time being passed, one comes to realize the real picture, that was blurred by the mask of amusements, hanging on the background wall of the medical field like a terrifying ghost.

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