Chapter 1: The Cell as a Unit of Health and Disease Flashcards
What proportion of the human genome is protein-coding?
The human genome contains about 3.2 billion DNA base pairs, of which 20 000 (about 1.5%) are protein-encoding genes.
What proportion of the human genome is involved in gene regulation?
The human genome contains about 3.2 billion DNA base pairs, of which about 80% binds proteins and is thought to regulate gene expression.
List the major classes of functional non-protein-coding sequences in the human genome.
- Promoter and enhancer regions that provide binding sites for transcription factors.
- Binding sites for factors that organise and maintain higher order chromatin structures.
- Noncoding regulatory RNAs (eg. micro-RNAs, long noncoding RNAs). More than 60% of the human genome is transcribed into RNAs that are never translated into protein, but which nevertheless regulate gene expression.
- Mobile genetic elements (eg. transposons). These represent up to one third of the human genome.
- Special structural regions of DNA (eg. telomeres, centromeres).
What are the two most common forms of DNA variation in the human genome?
- Single-nucleotide polymorphisms (SNPs).
- Copy number variations (CNVs).
Define epigenetics.
Epigenetics is the regulation of gene expression that is not caused by alterations in the DNA sequence. Epigenetics helps to explain why different cells can express different parts of the host genome.
Discuss DNA packaging in cell nuclei with reference to nucleosomes, histones and chromatin.
Segments of DNA bind to low molecular weight proteins known as histones.
Each segment of DNA bound to a histone is known as a nucleosome.
The nucleosomes then stack together and the DNA-histone complexes are collectively referred to as chromatin.
What is the difference between heterochromatin and euchromatin?
Heterochromatin describes densely packed and therefore inactive segments of nuclear chromatin.
Euchromatin describes cytochemically dispersed (or unwound) transcriptionally active chromatin. Histones can be remodelled to allow different segments of the genome to be accessible to RNA polymerases. This is thought to account for differing gene expression and different phenotypes in the setting of an identical genotype.
Describe noncoding RNAs (eg. micro-RNA and long noncoding RNA).
- Micro-RNAs (miRNA) are involved in posttranscriptional gene regulation. miRNA are able to modulate gene expression by binding to messenger RNA (mRNA) and ‘silencing’ it.
- Long noncoding RNAs (lncRNA) modulate gene expression in many ways to inhibit or promote gene expression. For example, lncRNA can bind to chromatin and thereby inhibit RNA polymerase from transcribing genes in the region.
What is the role of the rough endoplasmic reticulum?
Protein synthesis. Proteins are then moved to the Golgi apparatus for packaging and organising.
What is the difference between lysosomes, proteasomes and peroxisomes?
- Lysosomes contain degradative enzymes that break down macromolecules such as proteins, lipids and nucleic acids.
- Proteasomes chew up denatured proteins to produce peptides. They can be involved in antigen-presentation and often help to consume negative regulatory proteins.
- Peroxisomes break down fatty acids and produce hydrogen peroxide.
What is the role of the mitochondria?
Oxidative phosphorylation to produce ATP for cellular energy needs.
To a lesser degree it also produces intermediaries needed for anaerobic metabolism. Furthermore, mitochondrial damage often triggers programmed cell death.
Describe the structure and function of the cell membrane.
The plasma cell membrane is a bilayer composed of phospholipids, cholesterol and proteins.
Each phospholipid has both a hydrophobic tail and a hydrophilic head. They are arranged such that the hydrophobic tails interact with each other within the cell membrane while the hydrophilic heads are exposed to the aqueous cytoplasmic or extracellular environments.
The cell membrane is liberally studded with proteins and glycoproteins that are involved in:
- ion and metabolite transport;
- fluid-phase and receptor mediated uptake of macromolecules; and
- cell-ligand, cell-matrix and cell-cell interactions.
What are the two major mechanisms of endocytosis?
- Caveolae-mediated endocytosis describes non-coated invaginations of the plasma membrane and is sometimes referred to as ‘cellular sipping’ or potocytosis.
- Pinocytosis and receptor-mediated endocytosis allow consumption of larger molecules by pinching off a specialised area of plasma membrane coated by clathrins. These clathrin-coated vesicles are then combined with endosomes and lysosomes to digest their contents. In this way receptor-bound proteins are ingested.
What are the three major cytoskeletal proteins?
- Actin microfilaments, which polymerise to control cell shape and movement. - Intermediate filaments, which impart tensile strength and allow a cell to withstand mechanical stress. - Microtubules, which essentially act as cables along which motor proteins transport molecules, organelles and vesicles.
What are the three major types of cell junctions?
- Tight junctions, which create an occlusive barrier between cells to prevent molecules and ions slipping in between cells. - Desmosomes, which mechanically attach cells to their neighbours or to the extracellular matrix. Often formed by association between cadherins in the cell wall. - Gap junctions, which allow intercellular chemical and electrical communication as well as the exchange of ions and small molecules. Gap junctions are formed by multiple tiny pores made up of transmembrane proteins known as connexins. Permeability is reduced by low intracellular pH and elevated intracellular calcium concentration.
What is the morphologic difference between the rough and smooth endoplasmic reticulum?
The presence of membrane-bound ribosomes.
Discuss the role of mitochondria in energy generation.
Each mitochondrion has two membranes, an inner membrane folded into cristae, and an outer membrane.
Within the inner membrane is the core matrix. This is the site of the citric acid cycle (Kreb’s cycle) as the enzymes of the citric acid cycle are found in the core matrix. As hydrogen ions are produced they move into the intermembrane space, where they then reenter the core matrix to follow the electrochemical gradient. The reentry into the core matrix generates ATP in the intermembrane space.
List some common growth factors and their roles.
What are the stages of the cell cycle?
- G1 (presynthetic growth)
- S (DNA synthesis)
- G2 (premitotic growth)
- M (mitotic)
Figure 1-17 Robbins & Cotran
How is the cell cycle regulated?
The cell cycle is regulated by activators and inhibitors. Cell cycle progress is driven by cyclins and cyclin-dependent kinases (CDKs). There are checkpoints in the cell cycle that ensure DNA has been replicated without errors. These occur at G1-S and G2-M. The checkpoints are policed by CDK inhibitors (CDKIs) which can slow or stop the cell cycle.
Figure 1-18 Robbins & Cotran
