Cell Biology Concepts

Fundamentals of Molecular Cell Biology - Winter Semester 2024/25

• The study notes cover "The Cell and its Components"

The Cell as the Basic Unit of Life

• 2 structural types of cells: prokaryotes and eukaryotes
• 3 evolutionary types of cells: Bacteria, Archaea, and Eukarya
• Eukarya evolved from Archaea by endosymbiosis involving an α-proteobacterium becoming the mitochondrion and a cyanobacterium becoming the chloroplast

General Architecture of a Prokaryotic Cell

• Possesses one large cyclic DNA molecule (chromosome) and one or more smaller extrachromosomal DNA molecules called plasmids
• Has no internal membrane-bound compartments, with a few exceptions.

General Architecture of a Eukaryotic Cell

• Contains several large, linear DNA molecules called chromosomes
• Has several different types of membrane-bound compartments known as organelles

Eukaryotic Organelles

• Nucleus: Site of DNA synthesis and storage as well as RNA synthesis and synthesis of ribosomal subunits
• Mitochondrium: Involved in ATP synthesis, citric acid cycles, β-oxidation of fatty acids, and synthesis of Fe-S clusters
• Endoplasmatic reticulum (ER): Site of transmembrane and secretory protein synthesis and membrane lipid synthesis
• Golgi Apparatus (GA): Responsible for the distribution of proteins and polysaccharides via transport vesicles and protein glycosylation
• Lysosome (in animals): Organelle for the hydrolysis of proteins, nucleic acids, polysaccharides, and phospholipids
• Vacuole (in plants): Functions as a storage compartment for proteins, organic and inorganic ions, and is involved in the hydrolysis of various molecules
• Peroxisome: Site of oxidative degradation of long-chain and branched lipids and other organic molecules
• Chloroplast/Plastid (in plants): Conducts synthesis of monosaccharides from CO₂ and H₂O through photosynthesis

The Biomolecules of Life

• Nucleic acids: DNA and RNA
• Proteins: Enzymes and structural proteins
• Lipids: Membrane components, energy storage, carbon storage, and signaling molecules
• Carbohydrates: Energy and carbon storage
• Small organic molecules: Metabolites
• Inorganic ions and molecules: H⁺, Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻, phosphate, HCO₃⁻, O₂, CO₂, and many others

Nucleic Acids Details

• Nucleic acids (DNA, RNA) are biosynthesized from nucleotides
  • Biosynthesis of DNA = Replication
  • Biosynthesis of RNA = Transcription
• Schematic structure of all nucleotides including those that are not used for DNA and RNA biosynthesis (e.g., NADH, FADH₂, CoASH)
• All aromatic organic Bases in DNA and RNA are derived from purine and pyrimidine
• The monosaccharide residue in RNA is Ribose and in DNA is deoxyribose

Chemical Structures and Nomenclature of Organic Bases in DNA and RNA

• The presence of a 2'-deoxyribose unit in place of ribose, as it occurs in DNA, is implied by the prefixes "deoxy" or "d"
• For thymine-containing residues, which rarely occur in RNA, the prefix is redundant and may be dropped, and prefixes such as "ribo" may be used

Comparison of DNA and RNA

Chemical Structure of RNA

Chemical Structure of DNA

• 2 antiparallel strands

3D Structure of DNA

• Watson-Crick base pairing
• 1 helical turn = 10 bp = 3.4 nm

3D Structure of RNA

• Features include: stem, internal loop, hairpin loop, and bulge

Carbohydrates (Sugars)

• Are monosaccharides or multimers thereof (di-, tri-, oligo-, poly-saccharides).
• Monosaccharides are poly-hydroxy aldehydes (aldoses) or poly-hydroxyketones (ketoses)
• Biological monosaccharides are: trioses (C3), tetroses (C4), pentoses (C5), or hexoses (C6) e.g. ,

Aldoses

Ketoses

Cyclization of monosaccharides

• Occurs for pentoses and hexoses
• reaction of the carbonyl group with an -OH group = hemiacetal or hemiketal
• Generates two diastereomers: α and β and axial and equatorial groups

Derivatives of monosaccharides

• Result from reactions involving the aldehyde group or one of the OH-groups, -> Oxidation: alhehyd group is oxidised forming a "onic acid" Oxidation at terminal C-OH leads to uronic acid . Reduktion : the aldehyde- or keto group leads to sugar alcohol Reduktion : C-OH to C-H leads to deoxy sugar
• Substitution of -OH against -NH2 leads to amino sugar e.g,

Sugar acids

Sugar alcohols

Deoxy sugars

Amino sugars

Polymerization of monosaccharides

• Condensation reaction:
• ether 2 hemiacetal OH-groups leads to Acetals _HO O C-OH R HO HO Option A alcoholic

O C

Acetal

OH-group RR C OH Acetal

• ether 1 hemiacetal OH-group with 1 alcohol OH-group

O hemiacetal

C-OH OH-group R HO

O C

Option B hemiacetal

COHI HO R'

Acetal

Disaccharides

-Saccharose (non-reducing): α-D-Glucose ((α-D-Glc) residue and β-D-Fructose (β-D-Frc) residue ß-1,4 glycosidic bond

• Lactose (reducing): ß-D-Galactose (β-D-Gal) residue and ß-D-Glucose (β-D-Gic) residue.

Polysaccharides

• Cellulose: ( poly-β-1,4 glucose) main component of plant cell walls
• a-Amylose: ( poly-α-1,4 glucose) storage polysaccharide of plants

3D structures of polysaccharides

• Anomer used in the glycosidic bond and intramolecular H-bonds affects the 3D structure

Amylopectin (plants) and Glycogen (animals)

• Storage polysaccharide of plants and aminals
• Branch point: α-1,6 glycosidic Bindung" Amylopectin: 1 branch point per 20-30 Glc units Glycogen: 1 branch point per 8-14 Glc units

Chitin

• main component of fungal cell walls and arthropod exoskeletons (e.g. crustaceans, insects)
• ß-1,4 glycosidic bond β-D-N-Acetylglucosamine(β-D-GlcNAc) = Chitobiose residue => β-D-GlcNAc

Glycosaminoglycans (Mucopolysaccharides)

• used as lubricants and shock-absorbers in the extracellular matrix of animals

Lipids and Biomembranes

• Lipids are biomolecules highly soluble in organic solvents (e.g., methanol, chloroform, diethyl ether, diethyl acetate, toluene) and less soluble in H₂O
  • Proteins, carbohydrates, and nucleic acids are not lipids

Functions of the different Lipid Classes:

• Lipids are the main component of biological membranes ("lipid bilayer")
• Enable energy storage
• Signal transmission (extracellular: hormones, pheromones and intracellular: "second messenger" molecules)
• Transfer electrons from Electron transporters (e.g. ubiquinone in the respiratory chain)
• Enable Photoreceptors (e.g. retinal)

Biomembrane formation and life:

• Generation of electrochemical gradients by the body for energy production by chemiosmosis to maintain life activities.
• Enable the body to conduct compartmentalization of chemical reactions by avoiding undesired side reactions
• Molecules are selectively transported across the biomembrane and enables the cell to maintain optimal operating environment

Chemical structures and features of major lipids

Fatty acids

• Long-chain monocarboxylic acids (unbranched)
• Have saturated fatty acid where no C=C double bond exists
• Have unsaturated fatty acid where 1x C=C double bond exists
• Have · Nomenclature (always spaced by 1 methylene group -CH2-)
• Polyunsaturated fatty acid where ≥2 C=C double bonds exists -Carboxylic acid group position is C1 C=C double bonds are in cis configuration abbreviated notation: a : b (An,m,...) | Number of C atoms || Positions of the| | double bonds | number of | Example: Arachidonic acid 20:4(5,8,11,14)

Packing of fatty acid molecules

• Caused by "kink" in C-chain
• Caused by cis conformation of C=C double bonds =>
• Unsaturated fatty acid molecules cannot be tightly "packed" like saturated fatty acid molecules => fewer interactions between the unsaturated fatty acid molecules => lower melting point.

Triacylglycerides

• Lipids for energy storage

Glycerophospholipids and Sphingophospholipids

• Lipids for biomembranes

Isoprenoids

• multifunctional lipids

Steroids

• Lipid for biomembranes

Eicosanoide

• Lipid hormones

Aggregation

• When placed in an aqueous environment, lipid molecules aggregate as soon as they exceed a critical concentration (depends on the respective lipid molecule).
• critical micelle concentration (CMC) structure of the lipid aggregates is determines by the shape of any present Lipid molecules

Cholesterol

• Promotes the formation of liquid ordered regions within the bilayer

General information about the lipid compositions inside the biomembranes

• "Fluid Mosaic Model" of lipids, from 1972
• The biomembranes of different subcellular compartments differ from each other
• The Cytosolic lipid layer(Inner) has 2 lipid leaflets called leaflet (membrane) of of biomembranes for the of subcellular compartments, called the cytosolic side,and has extracellular/luminal lipid layer(outer side)
• The two leaflets: cytosolic lipid layer(Inner) and has extracellular/luminal lipid layer(outer side) are always different
• Newly synthesized lipid molecules are always originally incorporated on the cytoplasmic side of the biomembrane, but can get transported.
• The asymmetric distribution of lipids is accelerated under energy consumption (ATP hydrolysis) of flippases and floppases, in a short period of (days → seconds) types of
• transbilayer in this case "flips" lipid type from outer to the cytosolic by the protein"flippase" that requires ATP
• transbilayer in this case "flips" lipid type from cytosolic to the outer leaflet by the protein"floppase" that requires ATP
• Also exisits 'Scramblase" that moves lipids in either direction, toward equilibrium and requires not ATP

lons and hydrophilic molecules: transport of small moleucles across biomembranes

• Extremely slowly diffuse because inner of the lipid bilayer is hydrophobic.
• Membrane transporters to to enable easy transport hydrophobic molecules
• There are various molecules: sucrose, glucose, Cl-fructose, tryptophan ,urea ,indole, NH3.
• Passive diffusion:
  • simple diffusion that does not require transporters with an upward free energy
  • Passive diffusion has catalysed diffusion that use transporters with an reduced free energy
• Passive diffusion with an example of glucose: diffusion along a concentration gradient requires no energy
• Active transport: catalyzed diffusion of an ion/hydrophilic molecule S1 across biomembranes against a concentration gradient requires energy

Energy for transport of S1 can be supplied by:- - ATP hydrolysis (Uniport) - Transport of an second ion/molecule, S2 along its concentration gradient "Cotransport ,Symport, Antiport

In organs, physiological functions are achieved by the interaction of several transporter proteins

Example: the transfer of glucose from small intestine into the blood

Proteins Introduction

• Polymers of amino acids (monomers)
• Amino acid = α-Amino carboxylic acid

What defines a protein

In all proteinogenic amino acids (AA), wit exception of glycin, the α-C Atom is chiral and occurs exclusively in the L-form. The side chain of the amino acid is unique

Proteinogenic Amino Acids (I - IV)

• Non-polar side chains: Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Proline, Phenylalanine, Tryptophan
• uncharged polar, side chains: Serine, Threonine, Asparagine, Glutamine ,Tyrosine, Cysteine
• charged and polar side chains: with Lysine and Arginine. Aspartic acid and glutamic acids which are both negativelt charged. H is Histidine

Peptide Bonds

• Are build and made by a condensation reaction between the α-carboxylic acid group of one amino acid with the α-amino group of another.

• Isopeptide bond: reaction between α-carboxy group with amino group of side chain ",(K)", or α-amino group with carboxylic acid group",

• The molecule forms Peptide if its: contains ≤ 30 AAs connected via peptide bonds and the molecule is considered in this form a folded polypeptide The molecule forms a Polypeptide of chain": > 30 AAs connected via peptide bonds The fully functionally and structured molecule is a" Protein: folded polypeptide with or without chemical modifications

• pKs of the side chain in a free amino acid differs from its pKs in the peptide (influence of electrostratic repulsion and attraction ) that defines the molecule

Protein Structure

• The molecule shows two parts: N-Terminus and C-terminus

Protein Conformatin Forms

• Protein conformation of the Aminoacid: Arrangement of all atoms in space (3D structure)
• Native conformation of the Aminoacid molecule: 3D structure, in which the protein is functional "poperly folded"
• Denatured conformation of the Aminoacid molecule: 3D structure, in which the protein is non-functional ("unfolded")
• The peptide bond (all amide bonds) exhibits partial double bond character

The 3D structure of Proteins:

• Generates two diastereomers: a and ẞ"

• 3D structure of a cyclic monosaccharide : is chair-like

• axial group, equatorial group*

• Generates two diastereomers: axial and equatorial groups

• Protein is defined with - The degree of steric hindrance

Protein structrues' types

• Primary= AA Sequence
• Secondary a Helix, with axial group, equatorial group β sheet ( determined by the anomer used in the glycosidic bond and intramolecular H-bonds

Hairpin, Bulge

• Tertiary structure

Explore cell biology: ribosome function, chromatin structure, and signal transduction. Learn about nuclear localization signals and mitosis. Understand carbohydrate storage in plants and the function of glycogenin.