Ch 1 Flashcards
Plasma membrane functions are carried out by ____
Bound transmembrane proteins
Cell to cell communication uses chemical messengers systems that ____into ___fluid
Release secretions into extra cellular fluid
The process to generate membrane potential is
Diffusion of current carrying ions
What is the main difference between smooth muscle vs skeletal muscle?
SM have dense bodies attached to actin filaments
What is the role of rRNA in the nucleus?
Provide a site for protein synthesis
Defective sperm motility is secondary to which cellular component?
Microtubules
Which cellular transport mechanism required the most energy?
Vesicular transport
Desmosomes role in cells?
Forms junctions at epithelial cells
What percentage of human genome are protein encoding?
1.5%
What percentage of non coding proteins regulate coding regions?
80%
Central area of chromosome is called — and distal area is called —
Centromere
Telomere
What is the role of centromere? 2
Spindle apparatus attachment
Maintain heterochromatin
What are single nucleotide polymorphisms (SNP)?
Variant in single nucleotide position and are almost always bialleleuc eg one base different
Occurs mostly in non coding region (only 1% in coding region)
What is copy number variations (CNV)?
Genetic variations consisting of different number of large stretches of DNA eg deletion, duplication
What is epigenetics?
Heritable changes in gene expression that are not caused by variation in DNA sequence
What is a nucleosome?
DNA segment of 147 base pairs long, wrapped around central core protein (histone)
Inactive dense chromatin is called
Heterochromatin
Open, active chromatin is called
Euchromatin
What happens to chromatin during histone acetylation?
Opens up so transcription can happen (methylation condenses and inhibits transcription)
Which residues can be methylated? 2
Lysine
Arginine
What is the role of micro RNA (miRNA)?
Do not encode proteins, they modulate translation of target mRNA
Post transcription silencing of mRNA genes
What is the role long noncoding RNA (LC RNA) 4
- Gene silencing: restricting RNA polymerase leading to physiologic X chromosome inactivation (bind TF)
- Enhancer: expansion of transcription via gene promoters (promote TF)
- Stabilise protein complexes for gene expression
- Facilitate histone/DNA modification
What is the role of free ribosomes?
Cytosol protein synthesis
What is the role of smooth ER?
Steroid hormone and lipoprotein synthesis
What is the role of proteosomes?
Degrade tagged/denatured cytosol proteins
What is the role of peroxisomes?
Breakdown of very long chain fatty acids; generates H2O2
What are components of the cell cytoskeleton? 3
Actin
Keratin (intermediate filament)
Microtubules
What is the role of mitochondria? 4
- Generate ATP (Oxidative phosphorylation)
- Source of metabolic intermediates
- Synthesis of macromolecules eg heme
- Regulate apoptosis (intrinsic pathway)
What is the role of endosome?
Intracellular import and export out of cell
What is the cell membrane made of?
Lipid bilayer (hydrophilic head faces inside (later 1) and outside (later 2)
Which phospholipids face outside?
Phosphatydyl choline (PC)
Sphingomyelin (S)
Glycolipids (GL)
Inositol and cholesterol (both sides)
Which phospholipids on cell membrane are involved with eat me signal?
Serine
Which phospholipids on cell membrane are involved with serum cell integration? 2
Glycolipids and sphingomyelin
Which glycolipids form ‘lipid rafts’?
GL and S
What is the role of ‘lipid rafts’?
Maintain cell polarity
Intracellular tight junctions
What are the types of endocytosis? 2
- Caveolin mediated
- Receptor mediated
What is the role of caveolin mediated transport? 5
1.Internalisation of caveolate and bound molecules (Cellular sipping/potocytosis)
2.fusion with endosomes
3. Transmembrane delivery of folates
4. Transmembrane signalling
5. Cell adhesion (areas of lipid rafts)
Examples of receptors involved in receptor mediated endocytosis? 2
Transferrin R
LDL R
What is the coating in receptor mediated endocytosis?
Clathyrin
What is the role of clathyrin in receptor mediated endocytosis?
Formation of vesicles ‘clathyrin coated vesicle’
What is transcytosis?
Movement of endocytosis vesicles from apical surface to basal surface eg ingested ab in mother’s milk
What are the function of actin filament? 3
Vesicular transport
Epithelial barrier regulation
Cell migration
What filament/protein is the most abundant in cell cytosol?
G-actin
What is formed when G-actin polymerized?
F-actin
What is actin treadmilling?
F-actin: Subunits get added to (+) subunit (subtracted from (-) subunit)
What are intermediate filament?
Rope like polymers, 10 nm diameter filaments, made of keratin and nuclear lamin
What is the function of intermediate filament?
Tensile strength for mechanical stress (eg hemidesmosomes, desmosomes)
Vimentin is a filament associated with (cell)
Mesenchymal
Cytokeratin filament is associated with which cell
Epithelial
What are microtubules?
25nm, made of A & B tubulin, organised to hollow tubes, has (+) and (-) ends: dimers get added/taken away from (-) end
What is the function of microtubules? 4
1.Mooring lines for molecular motor proteins (Kinesin and Dynesin)
2. Mediate sister chromatid segregation during mitosis
3. Core of primary cilia: regulate cell differentiation
4. Motile cilia: bronchial epithelium or sperm motility
What are the molecular motor proteins and how do they work 2
Kinesin: anterograde transport (- to + end)
Dynesin: opposite
Which filament is involved in development of polycystic KD?
Microtubules
What is the function of tight junctions? 3
- Seal adjacent cells
; Prevent paracellular transport of ions and molecules - Maintain cell polarity by seperating apical and basolateral membrane domains
- Facilitate epithelial healing and inflammatory cell migration
What is the transmembrane protein in tight junctions? 2
Claudine and TAMP
What is the scaffolding proteins involved in tight junctions?
Zona occludens and cingulin
What is the transmembrane protein in adherent junction/desmosomes?
Cadherin
What are anchoring junctions?
Junctions that attach to filaments, are more basal than tight junctions
Eg adherent junctions
Desmosomes
Adherent junction: loss of epithelial E-cadherin gives rise to which pattern? Typically seen in which disease
Discohesive invasive pattern
Cancers eg gastric, lobular cancer breast
The transmembrane protein in hemidesmosomes is
Integrin
Which filament does desmosomes/hemidesmosome attach to
Intermediate filament
Which filament does adherent junction attach
Actin
What are focal adhesion complexes?
anchoring junction responds to shear stress and releases signals, localises at hemidesmosomes
What are communicating junctions?
Channels that permit diffusion of chemical and electrical signals
Eg gap junction
What are the pores/transmembrane protein in gap junctions called?
Connexons (Hexamer)
What influences permeability of gap junctions 2
Increase: calcium ion
Decrease: PH
What are the proteins that assist RER fold proteins?
Chaperones
Perinuclear Hoff is associated with presence of (organelle)
Golgi apparatus
What is the function of SER? 4
- Synthesis vesicles to carry proteins to Golgi
- Synthesis of steroid hormone and lipoprotein
3.catabolism of lipid soluble molecules - Sequesters intracellular calcium (signals apoptosis) (Sarcoplasmic reticulum for muscle contraction)
How are lysosomes formed 3
- Receptor mediated endocytosis
- Autophagosome fusion (via senescent organs/degraded proteins)
- Phagocytosis
Proteins that are destined for degradation by proteosome complex are tagged by (protein)
Ubiquitin
What is the process of ATP generation in oxidative phosphorylation?
H+ core membrane space gets pumped into intermembrane space (mitochondria). High H+ causes passive diffusion back into core membrane space: ATP generated
What is the mitochondrial uncoupling protein called? Function?
UCP-1 (Thermogenin): non shivering thermogenesis in brown fat (absence of coupling, cannot form ATP, produces heat only)
What is the Warburg Effect?
In rapidly dividing cells: they switch from oxidative phosphorylation to aerobic glycolysis
Increase uptake of glucose and glutamine
What products are produced in aerobic glycolysis?
2ATP
Lactic acid
Protein/lipid/amino acids
Membrane permeability transition proteins (MPTP) causes what kind of cell death?
Necrosis (leaks H+ out of mitochondria)
What are examples of receptors that belong to Epidermal growth factor (EGF)?
HER-2 (EGF-2) in breast cancer
Which growth factor stimulates embryonic development (pattern of tissue differentiation)?
Hepatocyte growth factor (AKA Scatter factor)
Where are Epidermal growth factors/transforming growth factors derived from?
Macrophages and keratinocytes
EGFR-1 is implicated in which cancers? 3
Lung
Breast
H&N
EGFR family has which enzyme activity
Tyrosine kinase
What is the function of EGF R family?
Proliferation (granulation tissue: EGF, hepatocytes: TGF-A)
Source of hepatocyte growth factor? 3 cell types
Fibroblasts, strommal cells in liver, endothelium
Platelet derived growth factor source?
Platelets
Macrophage
Keratinocytes
sMC
Endothelial cells
Function of PDGF?
Stimulates ECM synthesis
Which PDGF isoforms are already activated?
AA/BB/AB (CC/DD need activation)
Where is VEGF sourced?
Mesenchymal cella
Angiogenesis is mainly done by which VEGF?
VEGF 2
Which VEGF is responsible for embryonic vessel development?
VEGF B
What is the function of VEGF?
- Angiogenesis
2.lymphangiogenesis - Maintain normal epithelium (eg renal podocytes)
What is the main inducer of VEGF?
Hypoxia (via TF HIF-1)
What VEGFR receptor is expressed in pregnant women that lead to pre eclampsia?
VEGFR -1 (SFLT-1)
What are the finctional non-coding sequences 5
Promoter and Enhancer
Non coding regulatory RNA
Mobile genetic elements eg transposons
Telomeres
Centromeres
What is the CRISPR/Cas9 system?
High precision editing system
Cas9 is dual RNA guided DNA endonuclease enzyme
CRISPR clustered regularly interspaces short palindromic repeats
Homologous joining is superior
Which protein inhibits p53
MDM2
P53 is active in which state?
Hypophosphorylated
What is an autocrine signal?
Signal from cell to own receptor
What is a paracrine signal?
Cell signal to another neighbouring cell
What is endocrine signals?
Cell signals to another cell that is far away
What does signal transduction mean?
Signal molecule that is attached to receptor, will change receptor shape and send a 2nd messenger signal
When GDP binds to G-protein receptor, it is ___
Inactive
What are the types of G-protein?
Gi
Gq
Gs
What enzyme does Gq protein bind to?
Phospholipase C
What happens when Gq binds to Phospholipase C?
Cleaves Phosphatidyl 4.5- biphosphate
Into Diacylglycerol (DAG)
Inositol triphosphate
What is the fate of Inositol triphosphate (IP3) in the cell?
Diffuses into cytoplasm and ER: opens calcium channels (Can leaks out): depolarization
What is the fate of Diacylglycerol (DAG) in cell?
Binds to kinase C (cell membrane). Binds calcium: activates proteins by adding phosphoryl groups
What enzyme does protein Gs stimulate?
Adenylate cyclase
What does Adenylate cyclase do?
Takes 2P from ATP: transforms ATP into cAMP.
CAMP then binds to Kinase A (regulatory unit)
What does protein Gi for?
Inhibits adenylate cyclase
What do endonucleases do in cell?
Damage nuclear chromatin
Lactate dehydrogenase elevated suggests?
Cell death
The changes that happen to endometrium before period is
Apoptosis
Bcl-2 and NF-KB in tumour cells: function
Cell survival
What colour is lipofuscin?
Chocolate