Term
Integration 11
Describe the mechanisms allowing an increased use of glucose and fatty acids by a muscle cell when it goes from resting to exercising (5) |
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Definition
Causes an increase in AMP which leads to the 4 following things:
Increases glut 4 doorways
Activates muscle glycogen phosphorylase
Activates PFK-1
AMP dependent protein kinase which then phosphorlates acetyl coA carboxylase (turns it off) which turns off the production of malonyl coA (less inhibition of carnitine shuttle) |
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Term
Integration 6i
Glucose 6-phosphate dehydrogenase function |
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Definition
| First enzyme in the pentose phosphate pathway; makes NADPH; glucose 6-P to phosphogluconolactone (don't need to know) |
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Term
Integration 4h
Fructose 1,6-bisphosphatase function |
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Definition
| inducible enzyme; converts fructose-1,6-bisphosphate to fructose 6-phosphate in gluconeogenesis |
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Term
Integration 4i
Phosphoenolpyruvate carboxykinase (PEPCK) function |
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Definition
| fasting; turns OAA into PEP |
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Term
Integration 5a
Active when dephosphorylated or when phosphorylated & function: Phosphofructokinase-2 |
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Definition
| dephosphorylated; makes fructose 2,6 bisphosphate which promotes PFK-1 |
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Term
Integration 5b
Active when dephosphorylated or when phosphorylated & function: Pyruvate Kinase |
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Definition
| dephosphorylated; PEP to pyruvate; makes ATP |
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Term
Integration 6f
Pyruvate carboxylase
On during fasting or fed state, and function? |
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Definition
On during both
fed glucose to fat
fasting for gluconeogenesis
function is to convert pyruvate to OAA |
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Term
| Integration 6g Citrate Lyase function |
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Definition
| Citrate to OAA & acetyl CoA; takes an ATP |
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Term
Integration 7: Describe mechanisms that affect the storage of triacylglycerols in adipose tissue during the fed state.
Describe how adipocytes make the glycerol 3-phosphate needed for triacylglycerol synthesis, and how adipocytes can import fatty acids for attachment to the glycerol backbones. |
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Definition
Insulin increases glut 4 proteins in liver cells, with the glucose being then used for FA production
--
Adipocytes import FA's using LPL
Liver can phosphorylate glycerol --glycerol kinase--> G3P and can use glucose to make DHAP and <--Trios Phosphate Isomerase--> G3P (uses NADH to NAD+)
adipoctyes can only use glucose to make DHAP via <--Trios Phosphate Isomerase--> G3P (uses NADH to NAD+) |
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Term
| Integration 9: Describe the regulation of lipolysis in adipocytes during fasting |
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Definition
| Glucagon leads to PKA activation which activates HSL |
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Term
Integration 10
Describe the mechanisms by which your liver’s production of ketone bodies increases in the fasting state (10) |
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Definition
a decrease in the insulin level in the blood
and an increase in the glucagon level in the blood
↓
an increase in the supply of fatty acids from adipose
↓
an increase in beta oxidation of fatty acids in liver cells
↓
an increase in NADH and acetyl CoA in mitochondria of liver cells
↓
the high NADH (high NADH/NAD+ ratio)
↓
oxaloacetate being reversed to malate in TCA which is then used in the malate shuttle for use in gluconeogenesis
↓
oxaloacetate becomes unavailable for reaction with acetyl CoA
↓
the high acetyl CoA and unavailability of oxaloacetate
↓
increased use of the acetyl CoA to make ketone bodies
Also: mitochondrial HMG-CoA synthase is induced in fasting |
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Term
| Ketone Synthesis Review (4) |
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Definition
| 2 acetylCoA <--Thiolase--> Acetoacetyl CoA (coA gets thrown away) --HMG coA synthase--> 3-Hydroxy-3-Methylglutaryl CoA (HMG CoA) --HMG CoA Lyase--> Acetyl CoA (thrown away) and Acetoacetate |
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Term
| What two things activate PFK-1? |
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Definition
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Term
Cholesterol 2c
Steps we need to know for cholesterol synthesis (8) |
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Definition
Cytosolic acetyl CoA
HMG-CoA
Mevalonate
Isoprene donors
Squalene
Lanosterol
7-dehydrocholestero
Cholesterol |
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Term
Cholesterol 1
Draw the steroid ring system, label the rings and each carbon |
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Definition
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Term
| What does too much cholesterol in one's bile lead to? |
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Definition
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Term
Cholesterol 2a
Name tissues/organs that are the principal sites of cholesterol synthesis (2) |
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Definition
| liver, gonads (ovaries, testacles) |
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Term
Cholesterol 2b
Where does cholesterol synthesis occur? |
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Definition
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Term
Cholesterol 2d
What is the reducing agent in cholesterol synthesis? |
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Definition
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Term
Cholesterol 2e
Mitochondrial vs cytosolic HMG-CoA |
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Definition
mitochondrial to make ketone bodies
cytosolic used to make cholesterol or fat |
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Term
Cholesterol 2f
Give the reaction catalyzed by HMG-CoA reductase (3) |
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Definition
Control Point, Uses NADPH
HMG-CoA → Mevalonate
Takes 3 acetyl CoA molecules to make mevalonate |
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Term
Cholesterol 2g
Describe conversion of Mevalonate to The two interchangeable isoprene donors (3) (p. 641)
Draw Mevalonate
Draw an isoprene |
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Definition
Mevalonate is phosphorylated and drops an H and adds two phosphates to become 5-pyrophosphate mevalonate
It is then again phosphorylated and becomes 3-P-5PP mevalonate Costs 3 ATP; one for each phosphorylation
Carboxyl group CO2 and the 3-P is cut off to make Delta 3 Isopentenyl pyrophosphate ←→ dimethylallyl pyrophosphate
Isoprene:
CH2
||
C-CH3
|
CH
||
CH2 |
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Term
Cholesterol 2h
What constitutes squalene?
How many carbons are needed to make squalene? |
|
Definition
6 isoprenes in squalene, therefore 30 C’s
6 C’s needed to make 1 isoprene, therefore 18 acetyl groups and 36 carbons needed to make squalene |
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Term
Cholesterol 2i
Describe the cyclization of squalene to lanosterol (5 w/ lots of details) |
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Definition
| Squalene + O2 + NADPH –Squalene monooxygenase→ Squalene 2,3-epoxide (same oxygen) + H2O + NADP+ --2 Cyclase steps→ Lanosterol –Many reactions→ 7dehydrocholesterol + NADPH --reduction→ Cholesterol + NADP+ |
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Term
Cholesterol 3a
Predict the effect of an increase in the concentration of cholesterol in a cell on the cell’s expression of the gene for HMG-CoA reductase |
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Definition
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Term
Cholesterol 3b
Predict the effect of an increase in the concentration of cholesterol in a cell on the cell’s rate of degradation (proteolysis) of HMG-CoA reductase |
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Definition
| Increases degradation/proteolysis |
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Term
Cholesterol 3c
Predict the effect of phosphorylation of HMG-CoA reductase on its activity |
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Definition
| Deactivate; cholesterol produced in fed state |
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Term
Cholesterol 3e
Predict the effect of an increase in the concentration of AMP in a cell on the percentage of HMG-CoA reductase molecules that is phosphorylated |
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Definition
| Increase in HMG-CoA reductase phosphorylation |
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Term
Cholesterol 4
Describe the mechanism by which an increase in the concentration of cholesterol in a cell decreases the cell’s expression of the genes for HMG-CoA reductase and HMG-CoA synthase (3) |
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Definition
SREBP binds to SRE on DNA and causes transcription
Cholesterol/sterols make SREBP stay bound to ER membrane and not induce transcription
Sterols Increase HMG-CoA Reductase proteolysis/degradation |
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Term
Cholesterol 5b
Describe the reaction catalyzed by 7α-hydroxylase (6) |
|
Definition
cholesterol → 7α-hydroxycholesterol
control step in bile production
bile salts allosterically inhibit 7α-hydroxylase
NADPH is oxidized to NADP+ to make cytochrome P450 (Fe3+) become cytochrome P450 (Fe2+) which is used as a cofactor
O2 becomes H2O; O atom is reduced
An O is donated making an OH group |
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Term
Cholesterol 5c
Say how many carbons are in the structure of an unconjugated bile salt. Be able to recognize the chemical structure of an unconjugated bile salt. (3) |
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Definition
24 C’s
C 25, 26, 27 missing
C 24 becomes carboxyllic |
|
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Term
|
Definition
| conjugation = attachment of something that makes a molecule more water soluble (frequently done in detoxification) |
|
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Term
| Why is taurine not a true amino acid? |
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Definition
| It's not used in protein production |
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Term
Cholesterol 5d
Describe the conjugation of bile salts by the liver. Be able to recognize the chemical structure of a conjugated bile salt. (2) |
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Definition
Cholic Acid + ATP + CoA → AMP +PPi + Cholyl CoA
Cholyl CoA loses its CoA and becomes either Taurocholic acid or Glycocholic acid depending on which amino acid replaces the CoA |
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Term
Cholesterol 5e
Describe the enterohepatic circulation of bile salts. |
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Definition
| Bile salts released from gall-bladder in small intestine, 95% of bile salts are then later reabsorbed in ileum |
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Term
Cholesterol 6a
Describe the reaction catalyzed by cholesterol desmolase |
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Definition
| Cholesterol → pregnenolone |
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Term
Cholesterol 6b
Distinguish between corticosteroids (i.e. glucocorticoids and mineralocorticoids), androgens, and estrogens. Name an example of each, and give its origin. |
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Definition
Corticosteroids (c21)- steroids made by the adrenal cortex
Mineralcorticoids- important in how your body handles minerals
Aldosterone- save sodium get rid of potassium (when blood pressure is too low)
Glucocorticoids- important in how your body handles glucose
Androgens male 19C’s
Testosterone - Testes/Gonads
Estrogens female 18C’s
Estrogen - Ovaries/Gonads |
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Term
Cholesterol 6c
Describe the reactions catalyzed by aromatase (5) and 5α-reductase (3) |
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Definition
Aromatase cleaves carbon 19C
Androgen to estrogen
2 instances
androstenedione to estrone
testosterone to estradiol
--
5α-reductase
Testosterone → Dihydrotestosterone
DHT is an even stronger androgen than testosterone, found in hair follicles and in prostate gland
Inhibiting DHT and aromatase can prevent baldness and reduce enlarged prostate gland
Dihydro = two extra hydrogens |
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Term
Cholesterol 7c
Describe the synthesis of chylomicrons, their transport of dietary (exogenous) triacylglycerols, and their delivery of fatty acids to adipose tissue and muscle after a fatty meal (5) |
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Definition
pancreatic lipase, and colipase breaks down TAGs to FA’s and a 2-monoacylglycerol in micelles in small intestines
TAG’s resynthesized in enterocyte smooth ER
apoproteins made in rough ER
Chylomicrons then put in secretory vesicle by enterocyte golgi complex and secreted
then into lymph, then into blood where muscle and liver cell LPL uptake TAGs and the remnants are sent back to the liver |
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Term
|
Definition
Typically made from glucose
DHAP → G-3-P + FACoA → TG + Other lipids + ApoB-100 → VLDL |
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Term
Cholesterol 7f
Describe how, when lipoproteins are abundant in the blood, adipocytes can import fatty acids for the synthesis of stored fat. Describe the role of apo C2 in this process, and identify the source of the apo C2 |
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Definition
| HDL provides CII apoprotein (which activates LPL) |
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Term
Cholesterol 8
Describe the roles served by the apo(lipo)proteins of lipoproteins and give examples (4) |
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Definition
apo b 48 on a chylomicron:
- Make the surface more attractive to the water
- Forming the protein making a stable package for export
activating enzymes (eg. Apo CII, apo A1)
lipoprotein binding to a lipoprotein receptor can cause endocytosis (LDLs can accumulate if this does not occur) (eg. Apo B100, apo E) |
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Term
Cholesterol 9
Describe the conversion of chylomicrons into chylomicron remnants, and the fate of the chylomicron remnants |
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Definition
They release contents little by little as they travel through the blood at LPLs
Still contain a lot of cholesterol ester and cholesterol which can be used to make either steroid hormones or bile salts (in liver) |
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Term
Cholesterol 10
How do liver cells uptake Lipoproteins? |
|
Definition
LDLs are removed from the blood by receptor mediated endocytosis
Liver cells have chylomicron remnant receptors (requires that chylomicron have apo E from HDLs) LDL receptors for apo B-100 and apo E (liver cells have all cells that make steroid hormones) |
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Term
Cholesterol 11
Where do LDLs get apo B-100 and apo E? |
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Definition
| HDLs responsible for donation of both to LDLs |
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Term
Cholesterol 11
Describe the biochemical basis and clinical consequences of familial hypercholesterolemia |
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Definition
| Inheritance of lack of genetic coding for LDL receptors, causing cholesterol levels such as 400 or 500, can have heart attacks at age 20-30, if inherited from both parents, cholesterol can rise to 1000, children have heart attacks with this condition. |
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Term
Cholesterol 11
Describe the regulation of the expression of the gene coding for LDL receptors. (3) |
|
Definition
sterol regulatory element binding protein (binds to DNA and increases LDL receptor production)
additional gene with sterol regulatory element for making LDL
cells will get better at making and importing cholesterol when it is needed |
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Term
Cholesterol 12a
Describe how increased fiber intake can lower cholesterol (10) |
|
Definition
Can slow the absorption of fructose
Fiber decreases enterohepatic reabsorption of bile salts → amount of bile salts returning to the liver decreases → less inhibition of 7a-hydroxylase in liver cells → more use of intracellular cholesterol to make bile salts → intracellular concentration of cholesterol decreases → SREBP comes untethered and binds to DNA → expression of the gene coding for LDL receptors increases → more LDLs are removed from the blood → blood level of LDL cholesterol decreases |
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Term
Cholesterol 12b
Describe how statin drugs (and red yeast rice) can decrease the level of cholesterol in your blood, and why can this be unhealthy? |
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Definition
They inhibit HMG-coA reductase
Which also inhibits isoprene donors
Recommendation of Coq10 supplementation if HMG-coA reductase inhibitor is being taken to lower cholesterol |
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Term
Cholesterol 13
Describe the role of antioxidants in the prevention of atherosclerosis (4) |
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Definition
LDLs that stay in the blood too long will become oxidized
Oxidized LDLs are attractive to macrophages in the walls of arteries
When macrophages phagocytose too much oxidized LDL they then become foam cells and act deranged by sending off chemicals that they wouldn’t normally and draw cells and things that would not come normally and can cause plaque build up
Antioxidants prevent LDL oxidation |
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Term
Cholesterol 14
What cells make HDL? |
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Definition
| Liver cells make the HDL which is responsible for all that we're learning (since other cells make other lipoproteins that qualify as HDLs by definition but do do what liver HDLs do) |
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Term
Cholesterol 15
Describe the maturation of HDLs as they function in reverse cholesterol transport. Describe the reaction catalyzed by LCAT and its importance in this process. Describe the role of apo A1 in this process. Draw schematics for the structure of a lecithin and the structure of a cholesterol ester. (8) |
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Definition
HDL can remove cholesterol from the walls of arteries where it does not belong
Cholesterol to cholesterol ester establishes putting cholesterol in the core of an HDL
Cholesterol to cholesterol ester catalyzed by LCAT lecithin cholesterol acyl transferase
FA at position 3 needs to be donated from a lecithin molecule
Which is why lecithin granules are given to individuals with high cholesterol
[G – Fatty Acid
L
Y
C
E – Fatty Acid
R
O
L – P] – Choline (shorter)
Lecithin = Phosphatidyl (part of diagram in brackets) Choline
Apoprotein that activates LCAT is apo A1
Cholesterol –ester bond- FA is a cholesterol ester |
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Term
Cholesterol 16
Describe the interactions between HDLs and other lipoproteins in circulation. Describe the fate of HDLs. (3) |
|
Definition
CETP – Cholesterol Ester Transfer Protein transfers cholesterol from HDL to VLDL
Exchanges proteins with chylomicrons and VLDL
HDL then goes back to liver at the end of their lives |
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Term
Cholesterol 17
Describe the synthesis of vitamin D3, and the conversion of vitamin D3 into calcitriol:
Describe the conversion of 7-dehydrocholesterol into cholecalciferol (vitamin D3), and the conversion of cholecalciferol into calcitriol (1,25-dihydroxycholecalciferol). Describe some of the functions of calcitriol. (7) |
|
Definition
7-dehydrocholesterol converts to cholecalciferol (vit d3) by the energy from a photon
starts out by breaking the b-ring of 7-dehydrocholesterol, then becomes cholecalciferol which is converted in the liver to 25-hydroxycholecalciferol (calcidiol) where the kidney converts it to 1,25-dihydroxycholecalciferol (aka 1,25-(OH)2D3 or simply calcitriol) via PTH.
PTH induces 1-a-hydroxylase which converts calcidiol to calcitriol
UVB (for breaking the b-ring)
Calcitriol improves ability to absorb Ca++ from digestive tract
Enters enterocyte and forms transcription factor that binds to DNA, causes creation of calcibindin (protein that binds to calcium and causes the absorption of it) |
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Term
Cholesterol 18
Note the importance of monooxygenases in cholesterol metabolism (e.g. squalene monooxygenase and the hydroxylases and cytochrome P450 enzymes). Describe in general the reactions catalyzed by enzymes classified as monooxygenases or mixed function oxidases. Name and describe the structure of the cofactor required by all cytochromes. (7) |
|
Definition
General Monooxygenase function: O2 + S(ubstrate) + Electron Donor-XH2 (such as NADPH + H+) --> H2O + Electron Donor-X + S - OH
squalene monooxygenase converts squalene to squalene 2,3-epoxide which is a step in its conversion to lanosterol
all cytochromes have protein wrapped around a cofactor called heme
cytochromes important for bile salt production
hydroxylases important for tyrosine production from phenylalanine
cholesterol → 7α-hydroxycholesterol done by a 7a-hydroxylase, with cytochrome P450 as a cofactor
1-a-hydroxylase responsible for calcidiol to calcitriol |
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