Pathology

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1. The cell as a unit of health and disease

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The genome

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miRNA and lncRNA

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• miRNA. 22 nucleotides on average; at least 6000
  • join protein complex called RNA-induced silencing complex (RISC)
• siRNA (small interfering RNA). miRNA analogs artificially introduced into cells
• lncRNA. >200 nucleotides in length; at least 30,000
  • can bind to regions of chromatin, restricting RNA polymerase access

Cellular housekeeping

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Plasma membrane

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• glycolipids (particularly gangliosides): outer
  • cell-cell, cell-matrix interactions
  • inflammatory cell recruitment
• sphingomyelin: outer
• choline: outer
• serine: inner
  • normally inner; electrostatic scaffold for intracellular proteins
  • when extracellular (e.g. during apoptosis), becomes "eat me" signal for phagocytosis
  • in platelets, cofactor in clotting of blood
• ethanolamine: inner
• inositol: both
  • inner: electrostatic scaffold for intracellular proteins
  • hydrolyzed by phospholipase C to generate diacylglycerol and inositol triphosphate
• four general ways proteins interact with lipid bilayer
  • integral proteins. generally have positively charged amino acids in cytoplasmic domains to anchor to negatively charged phospholipids
  • attached to prenyl or fatty acids.
  • attached to glycosylphosphatidylinositol (GPI) anchors. GPI anchors are on extracellular face of membrane
  • noncovalent interactions with transmembrane proteins. extracellular proteins can associate with transmembrane proteins

Smooth endoplasmic reticulum.

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• site of steroid hormone and lipoprotein synthesis
• site of modification of hydrophobic compounds

Sites of catabolism

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• proteasomes. degrades tagged proteins
• lysosomes. degrades all kinds of macromolecules from phagocytosed microbes and damaged/unwanted organelles
• peroxisomes. contains oxidative enzymes (catalase, peroxidase); breakdown of very long chain fatty acids