Origin of Life & Cell Functions

Origin of Life. Basic Functions and Constituents of Cells

• During evolution, a eukaryotic organism equipped with a cytoskeleton and internal membrane systems engulfed/phagocytosed a prokaryotic organism, leading to a mutually beneficial relationship.
• Mitochondria originated when an aerobic prokaryote performing oxidative phosphorylation was internalized; chloroplasts came from prokaryotes performing photosynthesis; peroxisomes have a similar origin.
• Genetic information flows unidirectionally: DNA → RNA → protein → property (phenotype).
• Transcription occurs in the nucleus where DNA's genetic information is copied into a single-stranded RNA molecule via RNA polymerase, marking the first step in gene expression.
• Exons are coding sequences of genes that form part or all of a gene product, separated by non-coding sequences called introns in eukaryotes.
• During transcription in eukaryotes, introns get transcribed as messenger RNAs, and are cut out from the transcript before translation.
• Introns are nucleotide sequences in a gene that do not participate in encoding the protein product; in eukaryotes, introns are transcribed but removed before translation.
• RNA maturation involves post-transcriptional modifications in eukaryotic cells, converting primary transcript RNA into mature RNA in the nucleus; this includes 5' end capping, 3' poly-adenylation, and RNA splicing.
• RNA splicing, a post-transcriptional process, removes introns and covalently joins exons to form the mature messenger RNA, and allows a single gene to code for multiple proteins.
• Translation occurs in the cytoplasm where a polypeptide chain is synthesized from an mRNA molecule containing genetic information.
• In the cytoplasm, the ribosome reads mRNA bases as triplets.
• The genetic code defines the relationship between base triplets and amino acids in the polypeptide.
• Heterotrophs are organisms which synthesize ATP by degrading organic material, and all animals, protozoans, fungi, and most bacteria are heterotrophs.
• Autotrophs use sunlight or simple oxidative processes as energy sources to produce ATP: plants and certain bacteria are autotrophic. -Prokaryotes are cells without a nucleus, where the genetic material is in the cell plasma , bacteria and cyanobacteria are considered prokaryotes.
• Eukaryotes are living organisms with a separated nucleus, internal membrane system, and cytoskeleton; most organisms including unicellular eukaryotes, plants, animals, and fungi belong to this group.
• Primary biogenic elements (C, H, O, N, P) make up 98% of cells, and they form the bulk of organic matter and water.
• Secondary biogenic elements which include S, Fe, Cl, Na, K, and Ca make up about 2% of cells.
• Organic substances, formed by joining several carbon atoms, include carbohydrates, fats, and proteins.
• Amino acids contain amino and carboxyl groups; proteins of most living cells are built from 20 different a-amino acids.
• Deoxyribonucleic acid (DNA), the hereditary material, is constructed of two polynucleotide chains forming a double helix which are bound by hydrogen between complementary bases.
• DNA's role stores information, transmitting it to daughter cells, and indirectly controlling protein synthesis.
• Ribonucleic acid (RNA) is a polymer of ribonucleotide units, with ribose sugar and adenine, cytosine, guanine, and uracil bases.
• The major RNA types are messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and small nuclear RNA (snRNA).
• Messenger RNAs (mRNAs) transmit genetic information from DNA to proteins.
• Ribosomal RNAs (rRNAs), with ribosomal proteins, build ribosomes.
• Transfer RNAs (tRNAs) transport amino acids to ribosomes for translation.
• Small nuclear RNAs (snRNAs) are involved in mRNA splicing.
• Small interfering RNAs (siRNAs) and microRNAs (miRNAs) regulate gene expression.
• Some viruses have genomes composed of RNA.
• Cytoplasm fills the cells where metabolic processes occur, characterizing all cells.

Cell Membrane, Intracellular Compartmentalization

• Lipids are organic compounds that are soluble in apolar solvents that include neutral fats and phosopholipids.
• Amphipathic molecules contain apolar and polar moieties.
• Amphipathic molecules in water form a micelle.
• Polar molecules have unequal charge distribution and readily interact with water (hydrophilic).
• Apolar molecules do not undergo charge separation and do not significantly interact with water.
• Cell cortex is a three-dimensional protein network on the intracellular side of the cell membrane: composed of actin filaments, actin-binding proteins, and spectrin dimers in some cells; maintains membrane integrity, determines cell shape/motility, and regulates membrane proteins functions.
• Disruption of the cell cortex structure can lead to pathological conditions.
• Glycocalyx is a viscous coating layer on the extracellular side of the cell membrane and composed of carbohydrates, it plays a role in cell surface protection, adhesion and signal transduction.
• The glycocalyx can help immune cells differentiate between self and non-self cells or help pathogens enter cells.
• Asymmetry in the lipid bilayer occurs, and the lipid composition of the outer and inner layers is different, which affects membrane curvature and cell shape.
• Scramblases facilitate random lipid shuffling, while flippases and floppases are active, specific transporters.
• Lipid rafts are cholesterol-, glyco- and sphingolipid-rich domains in the cell membrane that have lower fluditiy which assemble/segregate proteins to regulate signal transduction processes.
• Signalosomes are supramolecular protein complexes regulated by protein-protein interactions, the compositon changes dynamically in space and time which ensures specificity of signal transduction.
• Endoplasmic reticulum (ER) is an intracellular membrane system in the cytoplasm located near the nuecleas, the surface of the rough ER binds ribosomes which transport proetie that need to end up on the membrane.
• The smooth ER lacks ribosomes and handles metabolic reactions and detoxification.
• Golgi complex is composed of stacked cisternae, having a polarized organization which modifies proteins from the ER, sorting and shipping them..
• Lysosomes are membrane-bound organelles containing acid hydrolases for intracellular degradation.
• Peroxisomes are membrane-bound organelles that use enzymes to decompose substances, and nuetralizes hydrogen-peroxide by converting it to H2O.
• Storage diseases arise from lysosomal dysfunction due to inherited mutations.

Passive Transport Processes

• A lipid-water partition coefficient characterizes hydrophobic character and measures a molecule's concentration in lipid versus water phases.
• Passive transport is material flow through biological membranes that doesn't require cellular energy, driven by concentration and electric potential differences.
• Facilitated diffusion uses specific proteins to transfer substances through biological membranes without direct energy input.
• Glucose uniport is a type of facilitated transport that does not require ATP and transports glucose down the concentration gradient.
• Ion channel gating is when the appropriate trigger causes a conformational change in the protein which makes it transition among different conducting and non-conducting states.
• Ion channel selectivity is when the passage of one or some ion species is allowed through the pore.
• Voltage sensors respond to changes in membrane potential by conformational changes in the pore.
• Gap junctions serve as non-selective channels connecting neighboring cells, allowing small molecules passage and contributing to electric synapses.

Active Transport Processes. ABC Proteins, SLC Proteins

• Active transport uses energy from ATP hydrolysis or ion flow to transport molecules against their concentration gradients.
• Secondary active transporters use the electrochemical potential difference of an ion for transport. E.g. glucose-Na+ symport, amino-acid-Na+ symport
• The Na+/glucose symporter transports 2 Na⁺ and one glucose molecules into the cells.
• V-type transporters transport protons into membrane enclosed organelles.
• P-type transporters gets phosphorylated transiently and the change in conformation can create ion gradients.
• ABC proteins bind and hydrolyze ATP and forms substrate binding sites which transport substrates across membranes.

Calcium Homeostasis

• Plasma membrane Na+/Ca2+ antiport (NCX) uses the electrochemical gradient of Na⁺ to transport Ca2+ out of the cytosol, and contributes in resting Ca2+ concentration in cardiac myocytes.
• Plasma membrane Ca2+ ATP-ase (PMCA) primary active transporter that exports Ca2+.
• SERCA is located and transports Ca2+ the reticulum.
• Ryanodine receptor (RYR) channel located in the membrane of the sarcoplasmic and endoplasmic reticulum in muscle cells, and the ligand is Ca2+.
• IP3 receptor (IP3-R) located in the membrane of the endoplasmic reticulum, and the ligand is IP3
• Calmodulin is a cytosolic Ca2+-binding protein with 4 Ca2+ binding sites having EF-hand structure which binds Ca2+, which then interacts and activates proteins.

Osmo-, Volume and pH Regulation

• The pump-leak model of osmo- and volume regulation is homeostatic and regulates cell volume in isotonic medium and reduces ion content cells
• RVD (Regulatory volume decrease) mechanism is induced by cell swelling in hypotonic medium and which reduces the cell volume
• RVI (Regulatory volume increase) mechanism is induced by cell shrinkage in hypertonic medium and which increases the cell volume.
• Steady-state pH of the cytosol is at the rate of base efflux
• Na+/H+ antiport mediates the influx of Na⁺ and the efflux of H⁺ function is the regulation of the cytosolic pH.
• Cl-/HCO3- antiport mediates the influx of 1 Cl- into, and the efflux of 1 HCO3 during one duty cycle.

Cytoskeleton

• Cytoskeletons provides stability for cells, is involved in Intracellular processes. It consists of filaments of various thicknesses.
• Microtubules is about long cylindrical structure which assembles in their GTP-bound state, used by eukaryotic cells to organize their cytoplasm, They are dynamic structures.
• Tubulin is a the protein subinits of microtubules, Alpha and beta tubulins form molecules . They can also form rings where microtubules start from.
• At its growing end, a microtubule is made up of tublin subinits, and this forms the GTP cap which stabilizes the + end.
• Colchicine plant alkaloid which blocks polymerization, and can inhibit microtubules and their stability.
• Microfilaments are made up of globular actin which assmebles into polarized protofilaments with the + end joining an ATP-bound G-actin. The strucutre can be viewed as two parallel proftoilaments.
• Intermediate Filaments provides Cells and tissues with mechanical strength.
• Treadmilling where the position of tubulin dimers change, that are streamed from the positive end to the negative end.
• Motor protiens concert chemical energy, examples include Kinesin, Dynein, and Myosin

Cell-Cell Contacts

• Lamellipodia are sheet-like protrusions, the organization of which is directed by monomeric G protiens.
• Actin sequestering proteins proteinas that bind to actin and modifty dynamic assemby.
• Actin Binding Toxins binds actin and can block the assemble
• Fibronectin are matrix proetins, the primary functions are to anchor and regulate shape
• Integrins, with heterodimer sequences, that bind together at extracellular regions form interactions and form signlalings.
• Cadherin are a family of protiens that adhear a cell to another and forms Junctions.
• In RGD presentation, the RGD motif is composed of aninmo acids the binding cites are exposed only if proteins are deactivated
• selectings bind the carbohydrates group og gycloprotines expecsessed on tehe surface, forming caton dependent bindings.
• During extravasation the expersiosn is increased. Then White blood cells, anocred and squeezed from their sorroundings, contribute to local inflammations.

Energetics, Mitochondrion

• Metabolism is the process to material uptake, conversations and discretion of the subtances involved
• Aerobic requires o2 presence, or the organism requires o2 for its metabolism. Anaerobic, the opposite
• Glycolysis is a catalyzed break down reaction, stores atp.
• Oxidative phosphorylation has products that accumulate the outside inner meme bran, it flows back and synthsizes atp from add and inoganic phostphte.
• ATP stores chemical energy in living organism
• AtP synthese are localized memebraine conplexes that catalyze the synthesis of ATP

Nucleus, Chromatin

• Nucleuos is the location of the syntheses of RNAS
• Euchromatiin is active, hetero charmain is inactive during iphase Histons are basic amino acids, and are charged possetivly and so are associated negitivley. Histons Modulate structors and mke dna more accessable.
• nucleosome is a strand of Dna wound aournd a protiencor
• Chroamtin modigintation id the proicess of genes regulating the siding of nucloesiomes
• D base sensitivity is high sensiytivity in actve regulatry enviornmatns
• Cromsomes are basic units that very during the cell cycles Epigenom determines changes of gee expression. Patternn is heartairy in cells
• Pormother where rna plymerace will bind
• Enchancers enhance the amplification of the transcripts of a the genne

Transport of proteins synthesized on free ribosomes. Nuclear envelope, transport through nuclear pores

• Mito chondriall proteins are signal sequenced, diriecting them to matrix
• nucelar enbvelop is composed of two lipid byerss the outer contiuons to the ER
• nucleral lamin supprt the structure, transport of moules through necleoporns,
• importins tranpsport from complextes and facilitates impor , rans has mono g, is invoiclved in syncrintizing necar tramsprot, Rans- GAPS Selectivity is based on nuclear singal localization. Protiens will bear nuclear export signals.
• Ran GAPs help transport protiens for exprot

Intracellular membrane systems, trafficking

• A typical process for liver cell detoxification is the transportatioin from hydorphobit to hdrophillici where it it expelled from.
• Ribosomes is where ptotieins a synthesised. Found in both Eukaryotes and Prokaryotes The cells decomponisition by lussing in lysisomes i.e. autophaghy.
• A transaltionat modigications occur when the monomers reidisies are taken
• Er signgal sequencing is where sequences that bind sputums tht connect them to signal recognition recptors
• Classfication occurs in trans golginetworsk while the protiens stsy theough this pathway is the lack scerteted payway

Cel Cycle Mitosis Meosis, Mechanics of cell division

• In Cell Cycle it can divide into two phases, the resting period and the subsequent cell division Meisos, Cells Division which reduces the number of chromosones Interphase is A period not containing the the cycle. Nuclear division, in cell cycle which produces 2 cell type. divison happens in mitotic phase.
• In mittoic cecless the centriols dublicate, migrate and organize
• Kinetochore has spindles that attach the chromatids and divides.
• Cohesin serain sparate separate the chromosomes that is then followed up in cytosine phase.
• cLeave Furrow in cyskinessis , forms into rings, membebranes form in the platonic division.

Regulation of the Cell Cycle

• A checkpint where its eterminmed to begen the dna synth
• ubiquination has proeties and protien complexes. Utiuqitn attach chains and are then degraded.
• APC complex regularees mitosis, actives during ohose and binds with proertis that degrdes protetasomes.
• Cylin helps to regulate protien prression, the activicty is simulatatouos with cilcons
• the sub strate os phosphatoe which removess inhibininh phosphate from inactive.
• the active MPF is CYCLIN COMPLE>

Cell signaling I. General concepts. Nuclear receptors. G-protein couple receptors

• Signalling occurs, the the csele in endocrin glands srecures it to te bloodstram where its transported ever where
• Hormone extra cellular signals for the glands
• Autocrine Signalling is what it called when the secreted orignal is tarretting the sam cell, the cell
• paracirne Singaling the the molecule does not go into the blood stream rather reavh max distance by the molecules diving through them.
• Intracells receptor factor are trasncription factor. Theybind to spacifcn DNA sefuenxes
• the G protitne coupled recepotrs the receptors to trimeric g protits
• adenylcyclase and protein kinaseA is a catalyst from cAMP from ATP.
• Beta adrenerge receptor is a receptor that binds epiephrine and and stimulate and aid teougt protinen k

Cell signaling II. Receptor tyrosine kinases. The Ras/МАPK, РІЗК/Akt and PLC/CaMK pathways

• Kinase enzymes that link the energy. It has serine protein tyrisne
• Second msgere molcule tht rleay extracellular recotpors, degraded or uot inte cal stores
• The RTK has enymicat activaoty and activated dimeers
• The ras a monetrmetiic g ptorein that has swhitch,

Cell Signalling III Pathways to the Nucelus

• Cytokine is when the cell surface is receivevers after being acticated by cttoines
• Jak (Janus Kinase) are to a trasduce to the cytokine, recptor and actuvate a trasnpciption factor.
• STAT TRanpsuces and are factos that actvate at their tyrisne, TGF B RECETOS The few ceptive which have inrensici serine threoanine kinase activity, interprt mesafrs from wide vaietives of ligand.
• wnt the signal that bind to its recepto then b catenin is suspeded.
• bate catein ha function in cell junctiuons, also for ell preliferatiion

cell communciation with nuerone in the sysmem

• Synspase in funtin woth other cell, that spreads through the nerual ce;;
• Chemical syanse in speacilazed juncitn betee celled, electirc signales casuese realease ot chemical.
• Eelxtic snpise has a impulse is trasmittesd raplidy throught the of the gap junbcttion
• Excitatotry synapse is a synapse iin whicj th aactuctation of neurton reector causes an increase of ca. the memebrane ptotion firi theshold. ex ACH seratonin , i inhibtory syanpse is wher the receprto is depolaixe causes shift mmeanre that decreases pototion.

Cell Fates Differentiation

• DIffenretioation is cell beoming more spesilaized and the gene expressuins atternc change
• morphage a uiffalbe subsatnce caeryuong otino, the concrreton The tumou supressing MYOD is is a trancpripion that is hterdimesed to cell differations.
• ONcogwne is a mutated form or or dysregular form of gees that control cell difiosn and growth Prooncogene geens tht drive cellcykces an and signale

CellFates call senensvencea death

• Refelicaitve senssesen haylck limit, are thenumner of of divsons an d ecell can have
• Immortixatiop n has e cells that re reelaase from a cell
• Telomres re enzyme is in eaxhv Dna repliaction cyole refills. th trincatied telmerore.
• breakage the chrormsl ends beoceme stickey due to shorrtein and attach eacrother
• apoptsosos a frmof clldeateht cells takje actibe prat

Cell Fates Stem cells

• stem cell: Is either undiffferntionates cells or partally differented , caon cide .
• totpotateen: Is ceelll that have potenial to make an enteire organimsn tht have the cpacoitu to diferancrt
• Pluri Potent: cell lthat can cude all tissues. except the tissues
• multipotetn, and unimpotent stem cells they can renwwe and regenerate damaed Tissies,
• Stem cell lnicie a microenibroemtne where stem cells can produce and live. Erthopotien, is hormone thaa gow cell in cell theidney. stimu;tes cel TOURMORSTEM CELLS THT CAN COJUMR FROM AN CE:LLL