Metabolism 2 Flashcards
What particles have ApoB100?
VLDL and LDL
What is steatorrhea?
Fat in the stool.
What particle(s) have ApoB48?
Chylomicrons
What are the three proteins on the surface of chylomicrons? How did they get there?
ApoB48: intestinal mucosal cells put it on
ApoCII: HDL puts it on
ApoE: HDL puts it on
What is the fxn of ApoE?
Recognized by liver.
What is the fxn of ApoCII?
Activates Lipoprotein Lipase which converts TAGs into FAs and moves the FAs into cells. This happens in the blood stream.
After a chylomicron docks to LPL, where does it go, and how has its composition changed?
It goes to the liver (ApoE).
Before LPL TAGs > CE.
After LPL TAGs < CE.
What is the rate limiting step in the FA oxidation process?
The carnitine shuttle.
How does Acyl-CoA get into the mitochondria?
- Acyl-CoA > (CATI) > Acyl-Carnitine
- Diffuse through outer membrane
- Transporter to get into inner membrane
- Acyl-Carnitine > (CATII) > Acyl-CoA
What are four things to know about normal beta-oxidation?
- Four step cycle
- 2 carbons cleaved at each step
- Acetyl-CoA all go to TCA
- NADH, FADH2 go straight to ETC
What is the trick in cis-double bond unsaturated fatty acid oxidation?
Turn the cis- into a trans- and then proceed as normal. You lose 1 FADH2.
What is the trick to odd # FA oxidation?
Add an extra carbon. Use a coenzyme that uses B12.
VLCFAs- how are they oxidized?
In peroxisome. It’s very similar to Mito oxidation, but it produces no FADH2.
Where does Beta-oxidation occur?
matrix of mito
What cell types cannot use ketones as fuel?
Liver and RBC.
Where are ketone bodies made?
Primarily in the liver.
What is the affect/correlation of glucagon and fatty acid synthesis?
When glucagon is present, you are not making FAs bc you are burning them.
What is the rate limiting step in FA synthesis?
Acetyl-CoA carboxylase (ACC).
How does Acetyl-CoA get out of the mito matrix?
It becomes Citrate
What cancer drugs are being explored around citrate?
Citrate Lyase: it turns Citrate back into Acetyl-CoA in the cytoplasm. This is important bc Acetyl-CoA in the cytoplasm is used to make FAs, which are needed for lipids in aggressively growing cancers.
What does Acetyl-CoA Carboxylase do?
It turns acetyl-CoA into Malonyl-CoA
How does ammonia get from peripheral tissue to the liver? What are the 3 steps?
- Peripheral Tissues: Glutamate > (add NH4 and ATP) > Glutamine
- Liver: Glutamine > (H2O removes NH4) > Glutamate [loss of NH4]
- Glutamate > (NADP+ to NADPH) > alpha-Ketoglutarate [loss of NH4]
What regulates the urea cycle?
N-Acetyl-glutamate. This enzyme regulates Carbamoyl Phosphate Synthetase-1 which is the necessary step for citrulline production.
Can Acetyl-CoA make sugar? Why?
No. When Acetyl-CoA joins TCA it first joins with OAA. It loses 2 carbons, and then becomes OAA again. The net affect is no gain. OAA can make sugar.
What AAs can’t make glucose?
Leucine and Lysine
What is different about the branch chain amino acids? What are those AAs?
Isoleucine, Leucine, Valine.
They are not taken up by portal circulation; they are sensed by the brain an an indicator of nutrient/caloric intake.
Phenylalanine makes what AA? Are they both essential?
Phenylalanine make tyrosine. Phenylalanine is essential, but tyrosine is not… unless we have no phenylalanine.
How does PKU work?
Phenylalanine cannot make tyrosine bc of a defect in phenylalanine hydroxylase.
What neurotransmitter does tyrosine make?
Tyrosine > L-Dopa > Dopamine
*all catecholamines are made from tyrosine
Kinase
Uses ATP to add phosphates
Posphorylase
Adds inorganic phosphate without ATP
Phosphatase
Removes phosphate group
Dehydrogenase
Catalyzes oxidation-reduction reactions
Hydroxylase
Adds hydroxyl
Carboxylase
Transfers CO2 groups with help of biotin
What is the rate-determining enzyme for de novo purine synthesis?
Glutamine-phosphoribosylpyrophosphate (PRPP) amidotransferase
What is the RDE for de novo pyrimidine synthesis?
Carbamoyl phosphate synthetase II
What is the RDE for the urea cycle?
Carbamoyl phosphate synthetase I
What is the RDE for fatty acid synthesis?
Acetyl-CoA carboxylase
How do you treat gout? By what mechanism does this work?
Use allopurinol. This inhibits xanthine oxidase, creating a back up of hypoxanthine and xanthine, both of which are more water soluble.
What are the 3 C’s that you always confuse? What do they do?
- Citrate: the way to get carbons out of mito matrix, used for FA synthesis.
- Citrulline: in urea cycle, citrulline gets carbons out of the mito matrix. Carbamoyl phosphate is added here, and this is the RDS for the urea cycle.
- Carnitine: Acteyl-CoA > Acetyl-Carn > enters mito matrix > Acetyl-CoA. There is a carnitine acyltransferase that puts the carnitine on.
What is the RDE for cholesterol synthesis?
HMG-CoA
What AA does the muscle release, and why?
Alanine bc it can carry a N.
What enzyme is used for the ping-pong? Which pathway does this go to?
PLP. This is used for the urea bc there is the N to get rid of.
What AA does muscles always end in?
Alanine.
What does N-Acetyl-glutamate do?
It regulates CPS-1 which starts the urea cycle.
What is the function of the salvage pathway in terms of the AA pathway? What is the enzyme that does this?
It tries to put a a sugar onto a base, -eg turn AMP into a purine. HGPRT [the lesch-nyman enzyme].
Explain the function of SREBP-2.
SREBP-2 is the TF that transcribes HMGBT CoA reductase, which is the enzyme used in cholesterol synthesis. It is activated when the cholesterol levels are low.
HMG CoA Lyase vs. Reductase, what’s the deal?
Lyase: ketone bodies
Reductase: cholesterol
What makes heme?
porphyrin + Fe2+ = heme
Where is heme synthesized?
- Liver (which produces CP450)
2. Erythrocyte-producing cells of bone marrow
What is the committed step in heme synthesis? What activates this? What inhibits this?
ALA (delta-aminolevulinic acid).
ALA synthase-1in liver. ALAS-2 in erythroid tissue.
Hemin
How are porphyrias inherited?
Autosomal dominant.
What is the difference between Transerrin, Ferrin, Ferroportin, and Hepcidin?
- Transferrin: uptake of Fe
- Ferrin: sequesters Fe in cells as Fe3+
- Ferroportin: efflux of Fe
- Hepcidin: secreted from liver when Fe is high to degrade Ferroportin
