lecture 2 biochemistry (week 2) Flashcards
what is a circadian rhythm?
ultradian rhythms
(less than one day) e.g. stages of sleep (REM= rapid eye movement, SWS= slow wave sleep patterns)
circadian rhythms – operate over 24 hrs e.g. sleep-wake cycle, body temp, plasma cortisol levels
infradian rhythms
(more than one day) e.g. female menstrual cycle
circannual rhythms
e.g. hibernation patterns
what is a crepuscular routine?
nocturnal but most active dusk and dawn - mice
how can the circadian rhythm be lost?
damage to the SCN
what is the siffre cave experiment?
no sunlight and constant temperature.
he emerged after 179 days
but he thought he had been in the cave for only 151 days
built in 25 hour biological clock
what are circadian rhythms’ affect on physiology?
0-6 hours –> deep sleep, lowest body temp, heart attacks most likely at 5 hours
6-12 hours –> cortisol release, fastest increase in BP, high alertness
12-18 hours –> best coordination, best reactions, highest body temp (18 hours)
18-24 –> highest BP, melatonin secretion
how is the circadian rhythm regulated?
main pacemaker is SCN
SCN receives info directly from the eye and rhythm can be reset by amount of light entering the eye; light is an important zeitgeber
light inhibits the release of melatonin from the pineal gland
blind individuals with intact eyes can reset circadian rhythm with light
how does regulation by light happen?
photosensitive retinal ganglion cells (pRGCs)
connects to the optic nerve
contain a receptor melanopsin (OPN4) which detects blue light 450-480 nm
computer devices can affect your “sleep hygiene”
what does the pineal gland do?
produces melatonin in the dark
light inhibits melatonin production
what is the melatonin pathway?
tryptophan –> 5-hydroxytrytophan –> serotonin –> N-acetylserotoin –> melatonin
what is the effect of melatonin?
melatonin has an important role in regulating the circadian rhythm, sleep control and signalling to other parts of the body
melatonin regulates seasonal cycles (circannual rhythms) controlled by the length of the daily photoperiod
reproduction, coat colour, fat accumulation, hibernation, etc.
melatonin is an antioxidant
describe the fruit fly experiment
larvae usually emerge at night
performed mutagenesis and looked for mutants that didn’t emerge from pupa at the right time– eclosion mutants (circadian rhythm mutants)
oscillator must be regulated by genes and their products
who won the nobel prize in 2017? and why?
jeffrey c. hall, michael rosbash and michael w. young
for their discoveries of molecular mechanisms controlling the circadian rhythm
isolation and identification of one of the mutants mentioned in last slide: the PERIOD (PER) gene in fruit flies
per protein accumulates overnight, which inhibits its own gene’s transcription
what are the role of transcription factors?
basic Helix-Loop-Helix transcription factors operate often as
heterodimers to bind to E-box motifs in target gene promoters
Core oscillator (Cry, Per, Clock, Bmal) and two oscillating ancillary loops
extra loops maintain accuracy and robustness of the system
system has evolved to cycle in ~24 hrs
system feeds into regulation of many output genes that control physiology
how do perturbed circadian rhythms affect physiology or lead to disease?
blood pressure should dip at night
taking antihypertensives in the evening reduces risk of heart attacks
clock-KO mice have a kidney pathology, and impaired glucose stimulated insulin secretion
motility of the GI tract, acid secretion, maintenance of the mucosa, and digestive enzyme production, oscillate in a circadian rhythm…linking GI function with expected meals
innate immune response varies over the day…cold symptoms worse in the evening
describe the sleep disorders
familial advanced sleep phase disorder (FASPD) is a circadian rhythm sleep disorder with early habitual sleep times.
individuals tend to feel tired in the early afternoon.
missense mutation (S662G) in thePER2gene was discovered which prevents phosphorylation by casein kinases Iδ and Iε (CKIδ/ε
