Steroids and Fat Soluble Vitamins Flashcards
vitamin D def
- prev in children is 9%, adults is 42%
- poor calclium absorption
- bone demineralization
- rickets in children
- osteomelacia in adults
- made synthetically from a precursor to cholesterol or from the diet in fatty fish, beef liver, cheese, egg yolks, some mushrooms
cholesterol
- membranes
- derivatives of this
- fits between phospholipids to reduce fluidity/permeability
- cholesterol rich rafts are important for membrane protein function and signalling
- bile salts, steroid hormones, vitamin D, coenzyme Q
cholesterol sources
- animal products in the diet
- we can not use plant sitosterols
- dietary cholesterol goes to liver as CE’s in chylomicron remnants
- endogenouse synthesis by liver but also in skin intestines, and kidneys
what does cholesterol synthesis use
- acetyl CoA from citrate lyase path
- NADPH from PPS and NADPH linked malate dehydrogenase
cytoplasmic acetyl CoA is converted to
HMG-CoA
-this is essentially the same mechanism to make ketone bodies
HMG-CoA reductase
- the major regulated step in cholesterol synthesis
- produces melavonate, a key building block of chol, from HMG-CoA
- inhibited by: freee cholesterol, phospohrylation by AMPK, and statin drugs
- controlled by rate of synthesis and degradation (has a 3.5 hour half life and free cholesterol inhibits its transcription and activates its degradation)
statin drugs
- work by mimicking substrate of HMG-CoA reductase
- they are inhibitors
what happens to mevalonic acid in cholesterol synth
-it is activated to form IPP (5C) which is an isoprene unit
how is squalene formed
-condensation reaction of isoprene units
what can be attached to proteins to anchor them into the membrane
-farnesyl groups
squalene monooxygenase
squalene to squalene epoxide
other important isoprenoiids that IPP condensations yield
- dolichol: sugar carrier
- ubiquinone: a mitochondrial electron carrier (coQ)
what kind of enzyme makes acetyl CoA
-thiolase
HMG-CoA synthase
-synthesizes HMG-Coa from acetyl coa in the cytoplasm
squalene monooxygenase and cyclase form
- a 4x ring structure (lanosterol)
- some additional modifications form cholesterol
How our body gets cholesterol
- new synthesis (liver, skin, and intestine)
- uptake of LDL via LDL-R
where does our body send cholesterol
- membranes
- conversion to intracellular CE deposits by ACAT
- release of VLDL (liver) and vhylomicrons (liver and intestine)
- excess is removed by HDL and LCAT
- converts it into bile salts, steroidogenic tissues –> hormones
cholesterol regulation
-free cholesterol stimulates ACAT and downregulates LDL receptor levels and HMG-CoA reductase
LDL levels can be controlled by
- ensuring proper LDL uptake by LDL-R
- decreasing synthesis (HMG-CoA reductase inhibitors)
- decreasing dietary cholesterol
- promoting excretion of excess cholesterol as bile salts
conversion of cholesterol into a steroid hormone
- cholesterol to pregnenolone
- pregnenolone to progesterone
- progesterone to either cortisol, corticosterone, or testosterone
- corticosteron can be made into aldosterone
- testosterone can be made into estradiol
cortisol
- from the adrenal cortex
- CHO, protein and fat metabolism
- suppresses immune response and inflammation
aldosterone
- from adrenal cortex
- regulate electrolyte resorption in kidney
estradiol
- from ovary adn testes
- secondary sexual characteristics and reproductive cycle
difference between protein and steroid hormones
- proteins work through second messengers from the cell membrane
- steroids directly alter transcription in the nucleus
what can you make from farnesyl -PP
- dolichol
- haem A
- CoQ (ubiquinone)
- farnesylated proteins (Ras, lamin B)
the conversion of cholesterol to bile salts
-this happens in the liver and begins with 7-alpha-hydroxylase which adds an -OH to the 7th position
fat soluble vitamins
- they are isoprenoids that can not be synthesized de novo or for which de novo synthesis may not be efficient (Vit D)
- includes A, D, E, and K
- not excreted, great excess can be toxic
vitamin A
-light reception and hormone
vitamin D
-hormne controlling calcium absorption
-
vitamin E
-antioxidant
vitamin K
-important cofactor for blood clotting
fat soluble vitamins are usually transported by
-lipoproteins
the three faces of vitamin A
- all trans retinal
- retinol
- retinoic acid
- comes from animal products and cleavage of provitamin A, carotinoids
vitamin A functions
- retinoic acid
- retinal
- retinoic acid: hormone important for growth and differentiation. activates transcription factors of the steroid receptor class
- retinal: bound to opsin, forms rhodospsin. light induces a cis to trans isomerization, causing dissociation and the conformational change in opsin is the first signal in vision
vitamin D
- we can synthesize with sufficient UV exposure
- this is a penultimate intermediate in cholesterol biosynthesis
- maintains blood calcium levels
- activates a vitamin D dependent transcription factor that promotes intestinal Ca++ absorption
- bone resorption
vitamin E
- important antioxidant
- some dietary fat is needed for the absorption of vitamin E from the gastrointestinal tract
- terminates free radical oxidation of unsaturated FA’s
vitamin K
-essential for blood clotting
-cofactorin gama carboxylation required for function of prothrombin and other clotting factors
-from plant sources and made by gut bacteria
-adult deficiencies are rare
-deficiency can cause hemorrhage in infants
-
vitamin K epoxide reductase inhibitors
- dicourmarins like warfarin and coumarol
- cause uncontrolled bleeding
- poison at high doses and low doses can treat thromboses
