Biochemistry - Cholesterol and Fat Soluble Vitamins Flashcards
What is the ratio of cholesterol:sphingolipid in lipid rafts?
~1:1
Name four important cholesterol derivatives.
Bile salts, steroid hormones, Vitamin D, coenzyme Q
Where do we get cholesterol?
Synthesis and from diet (animal products only - can’t use plant sitosterols)
What enzyme is involved in the major regulatory step in cholesterol synthesis?
HMG coA reductase.
Describe how HMG coA reductase is regulated.
- Statins inhibit (they mimic cholesterol and bind to allosteric site on enzyme).
- Free cholesterol inhibits allosterically, as well as increases enzyme degradation and decreases transcription of the enzyme gene.
- Glucagon and epinephrine inhibit via phosphorylation.
How many carbons is an isoprene unit (IPP)?
5
In cholesterol synthesis, what intermediate is created when three IPP units are combined? What important molecules are made from this intermediate?
Farnesyl pyrophosphate (FPP) - 15 carbons. Dolichol and ubiquinone are made from this.
What is the enzyme 7-alpha hydroxylase involved in?
Synthesis of bile salts. It adds a hydroxyl group to carbon #7 and —> bile salts!
Does the re-uptake of bile salts from the enterohepatic circulation require energy?
Yeah.
What is the carrier of steroid hormones in the blood?
Albumin.
Do steroid hormones activate intracellular second messengers or do they alter gene transcription?
Alter gene transcription because they are hydrophobic enough to pass through membranes and into the nucleus to bind to transcription factors.
Name the four fat-soluble vitamins.
A, D, E, K
Can the fat soluble vitamins be excreted in urine?
Nope
What are the three types of Vitamin A?
Retinal, retinol, retinoic acid.
What are the sources of vitamin A?
Carotinoids - must be cleaved to get vitamin A (carotinoid is basically two vitamin A’s linked head-to-tail)
What is retinoic acid involved in?
Important in growth and differentiation.
What is retinal involved in? Describe the process.
Involved in vision. Retinal combines with opsin protein to make rhodopsin. Light hits that, and induces a cis –> trans isomerization. The conformational change is the first signal in vision.
What results from vitamin A deficiency?
Night blindness
What is the immediate precursor in Vitamin D synthesis?
The penultimate product of cholesterol synthesis: 7-dehydrocholesterol.
Which three organs are involved in vitamin D synthesis and what are their respective intermediate products?
Skin makes D3, liver makes 25-hydroxycholecalciferol, kidney makes 1,25-hydroxycholecalciferol (most active form of vitamin D)
What does a healthy amount of vitamin D do?
Promotes interstitial Ca2+ absorption and bone formation.
What results from vitamin D deficiency? What results from toxicity?
Deficiency: poor mineralization of bones (Rickets)
Toxicity: Brittle bones - high vitamin D tells the body to get more Ca2+ in the serum, so calcium is resorbed from the bones. Also leads to renal stones and metastatic calcifications.
What is an important function of vitamin E?
It is an antioxidant and terminates free radical oxidation of unsaturated fatty acids.
What is vitamin K used for?
Gamma carboxylation of glutamate residues on prothrombin, so it can attach to the membrane for cleavage.
What enzymes are involved in gamma carboxylation of glutamate?
Vitamin K-dependent carboxylase does the gamma carboxylation. Vitamin K hydroquinone is a cofactor for this and Vitamin K epoxide is a byproduct. To regenerate Vitamin K hydroquinone from the epoxide, Vitamin K epoxide reductase makes Vitamin K quinone, and Vitamin K reductase makes Vitamin K hydroquinone for reuse.
Which LDL apoprotein binds to LDL-R?
B100
In what way does the mRNA for ApoB48 differ from that for ApoB100?
It is edited, resulting in a premature stop codon.
Which Apoprotein is recognized by LRP (remnant receptor)?
Apo-E