[P] Week 1: The Cell As a Unit of Health and Disease - Part 1 Flashcards
If pathology is defined as the study of suffering or the study of disease then what does “pathos” and “logos” stand for?
- Pathos: suffering
- Logos: study
- This is defined as the study of the structural, biochemical, and functional changes in cells, tissues, and organs that underlie disease
- It serves as the bridge between the basic sciences and clinical medicine
- It is the scientific foundation for all of medicine
Pathology
General vs. Systemic Pathology
- Alterations in specialized organs and tissues responsible for disorders that involve these organs
- Reactions of cells and tissues to abnormal stimuli and to inherited defects, the main causes of disease
- Systemic
- General
- The human genome contains around ____ DNA base pairs
- Within the genome, there are only about ____ protein-encoding genes, constituting just ____ of the genome
- 3.2 billion
- 20,000
- 1.5%
These genes are the blueprints that instruct the assembly of enzymes, structural elements, and signaling molecules within the 50 trillion cells that make up the human body
Protein-encoding genes
5 Major Classes of Functional Non-protein-coding Sequences
- These provide binding sites for transcription factors
- These are for factors that organize and maintain higher order chromatin structures
- These are described as jumping genes (e.g. transposons)
- Refers to telomeres (chromosome ends) and centromeres (chromosome tethers)
A. Mobile Genetic Elements
B. Promoter and Enhancer Sequences
C. Binding Sites
D. Special Structural Regions of DNA
E. Non-coding Regulatory RNAs
- (B) Promoter and Enhancer Sequences
- (C) Binding Sites
- (A) Mobile Genetic Elements
- (D) Special Structural Regions of DNA
- (E) Non-coding Regulatory RNAs
Note: (E) has no description in the transes but it constitutes the 5
Most of the genetic variations (polymorphisms) associated with diseases are located in what regions of the genome?
Non-protein-coding regions
Person-to-person variation susceptibility to diseases and response to environmental agents and drugs, is encoded in less than ____ of our DNA which is about ____ base pairs
- 0.5%
- 1.5 million
Refers to heritable changes in gene expression not caused by alterations in DNA sequences (phenotype diversity cannot be explained by DNA changes)
Epigenetics
What are the 2 most common forms of DNA variation in the human genome ?
- Single Nucleotide Polymorphisms (SNPs)
- Copy Number Variations (CNVs)
Single Nucleotide Polymorphisms (SNPs) or Copy Number Variations (CNVs)
- Are almost always biallelic (only two choices exist at a given site; e.g. A or T)
- There are more than 6 million of these
- Occurs across the genome (about 1% in the coding regions)
- A useful marker if co-inherited with a disease-associated pleomorphism as a result of physical proximity (linkage equilibrium)
- Displays a weak effect on disease susceptibility
Single Nucleotide Polymorphisms (SNPs)
Single Nucleotide Polymorphisms (SNPs)
- This element alters gene expression and disease susceptibility
- This variant has no effect on gene function or individual phenotype
- Genomic Regulatory Element
- “Neutral” Variant
Single Nucleotide Polymorphisms (SNPs) or Copy Number Variations (CNVs)
- Is biallelic and simply duplicated or deleted in some individuals
- Deals with complex rearrangements of genomic material, with multiple variants in the human population
- Is responsible for between 5 million and 24 million base pairs of sequence difference between any two individuals
- 50% of these involve gene-coding sequences
Copy Number Variations (CNVs)
- All cells of the body have (the same/different) genetic compositions
- Differentiated cells have distinct structures and functions that arise as a result of (lineage-specific/inheritance-specific) gene expression programs, depending on epigenetic factors
- The same
- Lineage-specific
TOF: Genomic sequences are translated but NOT transcribed
False (reverse; genomes cannot be translated as they are not proteins)
MicroRNAs (miRNAs) vs. Long noncoding RNAs (lncRNAs)
- Refers to small RNA molecules
- They do not encode proteins but rather modulate the translation of target messenger RNAs (mRNAs)
- Are critical regulators of developmental pathways as well as pathologic conditions (e.g. cancer)
MicroRNAs (miRNAs)
MicroRNAs (miRNAs)
This is a mechanism of gene regulation in all eukaryotes
Post-transcriptional silencing of gene expression
MicroRNAs (miRNAs) vs. Long noncoding RNAs (lncRNAs)
- Contains more than 200 nucleotides in length
- They modulate gene expression
- They bind to chromatin regions to restrict gene coding
- There is increased transcription from gene promoters (e.g. cancer and atherosclerosis)
Long noncoding RNAs (lncRNAs)
The following are the roles of Long non-coding RNAs (lncRNAs) EXCEPT:
A. Gene Activation
B. Gene Suppression
C. Promotion of Ribosomal Modification
D. Assembly of Protein Complexes
C. Promotion of Ribosomal Modification (should be chromatin modification)
Gene editing advancements are associated with CRISPRs which stand for?
Clustered Regularly Interspaced Short Palindromic Repeats
Cas9 nuclease is an example of what kind of gene?
CRISPR-associated genes (Cas)
Cellular Constituents
- Are “disposal” complexes that degrade denatured or otherwise “tagged” cytosolic proteins
- The degradation of regulatory proteins or transcription factors can trigger the initiation or suppression of signaling pathways
Proteasomes
In antigen-presenting cells, the resulting short peptides are presented in the context of Class I or Class II MHCs to help drive the adaptive immune response. What component is responsible for cleaving the peptides into short ones?
Proteasomes
Cellular Constituents
- These are intracellular organelles containing degradative enzymes that permit the digestion of macromolecules
- Serves as the site of senescent intracellular organelle breakdown (autophagy) and where phagocytosed microbes are killed and catabolized
Lysosomes
Cellular Constituents
- These contain catalase, peroxidase, and other oxidative enzymes
- They play a specialized role in the breakdown of very long-chain fatty acids, generating hydrogen peroxide in the process
Peroxisomes
The Fluid Bilayers of Amphipathic Phospholipids
____ head groups face the aqueous environment while ____ lipid tails interact with each other to form a barrier for the ____ diffusion of large or charged molecules
- Hydrophilic
- Hydrophobic
- Passive
The Plasma Membrane
- This can be phosphorylated, serving as an electrostatic scaffold for intracellular proteins
- This can also be hydrolyzed by Phospholipase C to generate intracellular second signals (e.g. diacylglycerol and inositol triphosphate)
Phosphatidylinositol
The Plasma Membrane
- These are located on the extracellular face
- These support charge-based interactions that contribute to inflammatory cell recruitment and sperm-egg fusion
Glycolipids and Sphingomyelin
Glycolipids
Glycolipids, including ____ with complex sugar linkages and terminal ____ that confer negative charges, support charge-based interactions
- Gangliosides
- Sialic acids
Membrane Transport (Passive or Active?)
- Oxygen (O2), carbon dioxide (CO2), and hydrophobic molecules diffuse easily through this
- Is impermeable to charged ions and is dependent on the degree of hydration
- It drives solutes via a concentration and/or electrical gradient between the inside and outside of the cell
Passive Diffusion
Membrane Transport (Passive or Active?)
- Plasma membrane transport proteins are required for the uptake and secretion of ions and larger molecules required for cellular function (e.g. nutrient uptake and waste disposal)
- It requires ATP as the solute moves against the concentration gradient
Active Diffusion
Membrane Transport (Proteins)
These create hydrophilic pores, which, when open, permit rapid movement of solutes (usually restricted by size and charge)
Channel Proteins
Membrane Transport (Proteins)
These bind to their specific solutes and undergo a series of conformational changes to transfer the ligand across the membrane
Carrier Proteins
Membrane Transport (Water Movement)
- H2O moves OUT of the cell
- H2O moves INTO the cell
- Hypertonic
- Hypotonic
Note: The point of reference is the PLASMA
Receptor-Mediated and Fluid-Phase Uptake Mechanisms
- Refers to the uptake of fluids or macromolecules by the cell
- The movement of endocytosed vesicles/intact proteins between the apical and basolateral compartments of cells (epithelial barriers)
- Refers to when macromolecules are exported out of the cell (vesicle is recycled to the plasma membrane)
- Endocytosis
- Transcytosis
- Exocytosis
Types of Endocytosis
- This makes use of caveolae, caveolin, and pinocytosis
- Contains major mechanisms for macromolecules bound to membrane receptors
- Caveolae-mediated Endocytosis
- Receptor-mediated Endocytosis
Types of Endocytosis
These are non-coated plasma membrane invaginations associated with GPI-linked molecules, cAMP binding proteins, src-family kinases, and the folate receptor
Caveolae (“little caves”)
Types of Endocytosis
This is a major structural protein of caveolae along with bound molecules and associated extracellular fluid
Caveolin
This is the intracellular scaffold (support) of proteins which has the ff. functions:
- Forms the shape of cells
- Maintains cellular polarity
- Provides a means for cell movement
- Maintains the positions of intracellular organelles
Cytoskeleton
Classes of Cytoskeletal Proteins
- The most abundant cytosolic proteins in cells
- Includes G and F actin (e.g. muscles)
Actin Microfilaments