steroids and prostaglandins (biochem) Flashcards
cholesterol
- structure
- no. of carbons
- how is it transported
- ring-based
- 27 carbon atoms
- by lipoproteins (LDL, HDL)
where is cholesterol synthesised?
pathway name
endoplasmic reticulum
HMG-CoA
what subclass of receptor are steroid receptors?
which protein are they associated with?
nuclear receptors
heat shock protein (HSP)
which receptors do steroids act on?
what do they do for gene transcription?
nuclear receptors
increase it
what type of hormones are steroids and prostaglandins?
lipid hormones
2 classifications of steroid hormones
where is each synthesised?
corticosteroids
- synthesised in adrenal cortex
gonadal steroids
- synthesised in ovary or testis
what are steroid hormones derrived from?
cholesterol
(by removal of carbon groups and addition of oxygen-containing groups)
3 subtypes of corticosteroids & major example of each
mineralocorticoids e.g. aldosterone
glucocorticoids e.g. cortisol
androgens e.g. DHEA
3 subtypes of gonadal steroids and example of each
progestogens e.g. progesterone
androgens e.g. testosterone
estrogens e.g. estradiol
steroid genenis diagram
what is the rate limiting step in steroid genesis?
which enzyme is involved?
cholesterol (C27)–> progestogens (C21) + C6
CYP11A1 (a cytochrome p450)
aka CP450 CSCC (cholesterol side chain cleavage)
where does CYP11A1 reside?
which 2 substances do its actions depend on?
inner mitochondria facing matrix
StAR
mitochondrial peripheral benzodiazepine receptors
what is the role of StAR?
where does it reside?
aids with intracellular transport of hydrophobic cholesterol
ovaries and testes
2 steroidogenic enzymes:
- cytochrome p450 (specifically CYP11A1/ CP450 CSCC (cholesterol side chain cleavage)
- HSD
which 2 enzymes does cytochrome p450 include?
17- hydroxylase
21 hydroxylase
what are the 4 types of gonadal cells?
Leydig cells
theca cells
granulosa cells
luteal cells
what do Leydig cells produce?
do they have 17B-HSD?
testosterone
no
what do theca cells produce?
do they have 17B-HSD?
androgens - but cannot produce testosterone and oestradiol
yes
what do granulosa cells produce?
do they have 17B-HSD?
oestradiol
yes
what do luteal cells produce?
progesterone & oestradiol
CAH - congenital adrenal hyperplasia
- inheritance
- what is the issue?
- what is the consequence of this physiologically
- autosomal recessive
- defect in StAR protein (also cytochrome p450CSCC and 21-hydroxylase)
- failure of steroid production
accumulation of large lipid droplets in adrenal glands
clinical features of congenital adrenal hyperplasia (CAH)
salt wasting crisis
issues with lung inflation
also:
i. ambigious genitalia
ii. natiuresus (weeing out lots of sodium)
iii. precocious puberty or failed puberty
iv. infertlility due to anovulation
v. virilisation
^^ all above due to 21-hydroxylase deficiency
vi. HTN
^^ due to 11-hydroxylase deficiency
what are prostaglandins synthesised from?
arachadonic acid
what is arachadonic acid?
what is it attached to?
which enzyme removes it from this?
(the material from which prostaglandins are synthesised)
- a polyunsaturated fatty acid
phospolipid membrane
phospholipase A2 - this is rate limiting step in synthesis of prostaglandins
arachadonic acid –> free arachidonate
what limits phospholipase A2?
lipocortin
what does COX do?
free arachidonate –> prostaglandin H2 (briefly G2 first)
what is the difference between COX1 and COX2
COX 1 - constitutively active
COX 2 - hormone responsive
what inhibits COX?
indomethacin
aspirin
other NSAIDS
what does prostaglandin rely on?
alcohol group at carbon 15
what enzyme can inhibit prostaglandin?
where is there lots of this?
15-hydroxyprogestaglandin dehydrogenase
lungs
myometrial contraction is a balancing act.
what are the relaxants/ contractants
contractants (Ca2+)
oxytocin
prostaglandins
relaxants (cAMP/ cGMP)
NO
relaxin
progesterone
