Lecture 4

Question 1

What are two types of physical damage to DNA?

Answer 1

Ionising radiation and Ultraviolet radiation

Question 2

What damage is caused by ionising radiation?

Answer 2

Water is broken to form H and OH free radicals which cause breaks in the DNA strand which can be misrepaired

Question 3

What damage does U.V. radiation cause?

Answer 3

Damages DNA bases where adjacent C’s and T’s become linked causing potential misrepair leading to cancer or death of keratinocytes

Question 4

What is a form of chemical damage to DNA?

Answer 4

Alkylation where aflatoxin B can cause liver injury at high doses, or G to T mutations underlying liver cancer

Question 5

What is a form of biological damage to DNA?

Answer 5

Dietary deficiency in B9 and B12 prevents DNA synthesis and repair causing megaloblastic anaemia

Question 6

What is a form of physical damage to lipids?

Answer 6

Crystal intake into lysosomes which then puncture activating inflammasomes and releasing hydrolytic enzymes

Question 7

What is a chemical form of damage to lipids?

Answer 7

Reaction of lipids with free radicals

Question 8

What is superoxide?

Answer 8

A oxgen diatomic molecule that is also a free radical and detoxified by superoxide dismutase to hydrogen peroxide and O2

Question 9

What is the enzymic reaction of hydrogen peroxide that occurs in cells?

Answer 9

Catalse detoxifies it to Oxygen and water

Question 10

What is the reaction that occurs between an OH radical and a Lipid?

Answer 10

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

Question 11

What are the sources of reactive oxygen species?

Answer 11

Oxygen therapy, Inflammation, UV radiation, Damaged mitochondria, radio therapy

Question 12

What is a biological form of damage to lipids?

Answer 12

Lipases are protiens that can cause damage to lipids as they digest them

Question 13

What is acute haemorrhagic pancreatisis?

Answer 13

Damage to exocrine cells occurs, resulting i nthe release of activated digestive enzymes including phospholipases and lipases which digest cell membranes and triglycerides

Question 14

What is a form of physical damage to proteins?

Answer 14

Heat as above 42 degrees proteins become denatured resulting in the release of heat shock proteins in an attempt to address the denaturation problems

Question 15

What is a form of chemical damage to proteins?

Answer 15

Glycation or the maillard reation where sugars are added to proteins due to high temperatures rather than enzymes.

Question 16

What are the steps in the maillard reaction?

Answer 16

Reversible schiff bases are generated, these then become irreversible amadori products, which then become advanced glycation end products

Question 17

What damage do amadori products cause to cells?

Answer 17

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

Question 18

What diseases to amadori products promote?

Answer 18

Cardiovascular disease, neurodegeneration and cataract formation

Question 19

What is a form of biological damage to proteins?

Answer 19

Proteases can cleave the extracellular matrix, causing cleavage to collagen in arthritis, elastin in emphysema, laminin during cancer invasion

Question 20

What are the two classes of reversible effects that damage can have on cells?

Answer 20

Acute intracellular oedema and abnormal storage

Question 21

What is acute intracellular oedema?

Answer 21

When the ability of the cell to regulate ion concentrations is compromised resulting in swelling which is initially reversible

Question 22

What is Abnormal storage?

Answer 22

Accumulation of products such as fat and glycogen resulting from either increased cocnentration or a reduced ability of hepatocytes to metabolism them

Question 23

What are the 5 types of adaptive responses cells have to deal with damage?

Answer 23

DNA damage response, Antioxidant response, Heat shock response, Unfolded protein response, hypoxia response

Question 24

What occurs in the DNA damage response?

Answer 24

p53 transcription factor will cause repair, cell cycle arrest or cell suicide

Question 25

What occurs in the Antioxidant response?

Answer 25

Nrf family of transcription factors are activated resulting in the making of proteins like catalase or SOD1

Question 26

What occurs in the heat shock response proteins?

Answer 26

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

Question 27

What occurs in the unfolded protein response?

Answer 27

Chaperone proteins are produced

Question 28

What occurs in the hypoxia response?

Answer 28

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