Lecture 4 Flashcards
What are two types of physical damage to DNA?
Ionising radiation and Ultraviolet radiation
What damage is caused by ionising radiation?
Water is broken to form H and OH free radicals which cause breaks in the DNA strand which can be misrepaired
What damage does U.V. radiation cause?
Damages DNA bases where adjacent C’s and T’s become linked causing potential misrepair leading to cancer or death of keratinocytes
What is a form of chemical damage to DNA?
Alkylation where aflatoxin B can cause liver injury at high doses, or G to T mutations underlying liver cancer
What is a form of biological damage to DNA?
Dietary deficiency in B9 and B12 prevents DNA synthesis and repair causing megaloblastic anaemia
What is a form of physical damage to lipids?
Crystal intake into lysosomes which then puncture activating inflammasomes and releasing hydrolytic enzymes
What is a chemical form of damage to lipids?
Reaction of lipids with free radicals
What is superoxide?
A oxgen diatomic molecule that is also a free radical and detoxified by superoxide dismutase to hydrogen peroxide and O2
What is the enzymic reaction of hydrogen peroxide that occurs in cells?
Catalse detoxifies it to Oxygen and water
What is the reaction that occurs between an OH radical and a Lipid?
The OH breaks a hydrogen bond to make a lipid radical, which then reacts with oxygen to make a lipid peroxyl radical. This the reacts with another lipid to generate a lipid radical and a lipid hydroperoxide. The lipid hydroperoxide then forms dmagning aldehydes and ketones
What are the sources of reactive oxygen species?
Oxygen therapy, Inflammation, UV radiation, Damaged mitochondria, radio therapy
What is a biological form of damage to lipids?
Lipases are protiens that can cause damage to lipids as they digest them
What is acute haemorrhagic pancreatisis?
Damage to exocrine cells occurs, resulting i nthe release of activated digestive enzymes including phospholipases and lipases which digest cell membranes and triglycerides
What is a form of physical damage to proteins?
Heat as above 42 degrees proteins become denatured resulting in the release of heat shock proteins in an attempt to address the denaturation problems
What is a form of chemical damage to proteins?
Glycation or the maillard reation where sugars are added to proteins due to high temperatures rather than enzymes.
What are the steps in the maillard reaction?
Reversible schiff bases are generated, these then become irreversible amadori products, which then become advanced glycation end products
What damage do amadori products cause to cells?
Binding to RAGE receptors causing inflammation
Generation of reactive oxygen species
inhibiting protein function
cross-linking, aggregating and precipitation proteins impeding things such as axonal transport
What diseases to amadori products promote?
Cardiovascular disease, neurodegeneration and cataract formation
What is a form of biological damage to proteins?
Proteases can cleave the extracellular matrix, causing cleavage to collagen in arthritis, elastin in emphysema, laminin during cancer invasion
What are the two classes of reversible effects that damage can have on cells?
Acute intracellular oedema and abnormal storage
What is acute intracellular oedema?
When the ability of the cell to regulate ion concentrations is compromised resulting in swelling which is initially reversible
What is Abnormal storage?
Accumulation of products such as fat and glycogen resulting from either increased cocnentration or a reduced ability of hepatocytes to metabolism them
What are the 5 types of adaptive responses cells have to deal with damage?
DNA damage response, Antioxidant response, Heat shock response, Unfolded protein response, hypoxia response
What occurs in the DNA damage response?
p53 transcription factor will cause repair, cell cycle arrest or cell suicide
What occurs in the Antioxidant response?
Nrf family of transcription factors are activated resulting in the making of proteins like catalase or SOD1
What occurs in the heat shock response proteins?
Heat shock factors are activating resulting in the formation of molecular chaperones which bind to denatured proteins preventing aggregation, and aiding in either the renaturation or the destruction of the protein
What occurs in the unfolded protein response?
Chaperone proteins are produced
What occurs in the hypoxia response?
Genetic sequences designed to help the cell survive in low oxygen environments are activated including things like glucose transportses, glycolytic enzymes erythrocyte and blood vessel development
