Term
| How do you make phosphatidic acid? |
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Definition
1. Glycerol/ glucose -> Glycerol 3 phosphate *From diet- glycerol + ATP + glycerol kinase *From glycolysis- glucose-> dihydroxyacetone Phos + NADH 2. GLycerol 3 phosphate + 2 activated Acyl-CoA + acyl transferase -> Phosphatidic acid *Chains are on C1 and C2
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Term
| In what synthesises is phosphatidic acid used? |
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Definition
TAG and glycerophospholipid
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Term
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Definition
1. Activated phosphitidic acid + P phosphatase -> DAG (P is removed from C3) 2. DAG + Acyl transferase + Acyl-CoA -> TAG |
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Term
| What determines what type of lipid is made? |
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Definition
| Acyl-CoA synthases and Acyl-transferases |
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Term
Activation of DAG for glycerophospholipid synthesis: |
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Definition
DAG activated by CDP Head group (alcohol) "attacks" P of CDP CMP is released =Activated glycerophospholipid Used for phosphotidylinostitol (and PIP2), cardiolipin, and phosphotidyl glycerol synthesis
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Term
| Head group activation in glycerophospholipid synthesis: |
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Definition
2 types: Head group activation and head group transfer 1. Head group transfer (PC/PE)
-Phosphorylate using ATP and kinase -Activate using CTP (cleave off PPi) -Add DAG (cleave of CMP)
2. Head group exhange (PE: PS and PC: PS) ex- PE + serine + PSS1 -> PS
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Term
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Definition
1. Decarboxylate PS -> PE 2. PE + 3 methyl transferase -> PC |
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Term
| Sphingolipid biosynthesis |
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Definition
1. Palmitoy-CoA + Serine -> β-ketosphinganine + CoA + CO2
2. β-ketosphinganine + NADPH -> Sphinganine + NADP 3. Sphinganine + fatty-acyl-CoA -> N-acylsphinganine + CoA 4. N-acylsphinganine + mixed function oxidase ->Ceramide w/sphingosine 5. Ceramide + glycerophospolipid (PC) -> sphingomyelin + DAG OR 5. Ceramide + UDP-sugar -> globo/ganglioside
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Term
What are the 4 stages of biosynthesis of cholesterol? |
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Definition
1. Condensation of 3 A-CoAs to form mevalonate 2. Activation of mevalonate to IPP 3.IPP condensing to squalene (5C to 30C) 4. Cyclization of squalene to 4 ring structure and reduction of some bonds to form cholestrol
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Term
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Definition
1. 2 A-CoA + thiolae -> Acetoacetyl-CoA + CoA 2. Acetoacetyl-CoA + A-CoA + HMG-CoA synthase -> β-Hydroxy-β-methylglutaryl-CoA 3. β-H-βMG + 2 NADPH + HMG-CoA reductase -> Mevalonate + CoA + 2 NADP |
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Term
| Activation of mevalonate (to IPP) |
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Definition
1. Mevalonate + ATP -> 5-Phosphomevalonate + ADP 2. 5-Phosphomevalonate + ATP -> 5-Pyrophosphomevalonate + ADP 3. 5-Pyrophosphomevalonate + ATP +decarboxylase -> [3-phospho-5-Pyrophosphomevalonate] + ADP -> CO2 + Pi AND IPP and DMAPP *[3-P-5PPM] is just intermediate, not found in cells |
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Term
| Cholesterol synthesis from DMAPP and IPP |
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Definition
1. DMAPP + IPP and prenyl transferase -> geranyl pyrophosphate + PPi 2. Geranyl pyrophosphate + IIP +prenyl transferase -> Farnesyl pyrophosphate + PPi 3. 2 FarnesylPPi+ NADPH + squalene synthase -> Squalene + NADP + 2PPi 4. Squalene + NADPH + O2+ (monooxygenase) -> Squalene 2,3 epoxide + NADP + H2O
5. Squalene 2,3 epoxide + cyclase -> lanosterol --> Cholesterol *monooxygenase is mixed function oxidase
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Term
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Definition
Liver uses ACAT to transport _______ to peripheral tissues Peripheral tissues use ACAT to aid in storage |
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Term
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Definition
HDLs Cholesterol transport back to liver Activated by ApoA-I |
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Term
| Major classes of lipoproteins |
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Definition
Chylomicrons VLDL LDL IDL
HDL |
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Term
| General characteristics of lipoproteins |
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Definition
-Hydrophobic core -Composed mainly of TAGs, cholesterol and esterified cholesterol -Contain various apolipoproteins
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Term
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Definition
-Used for transport of dietary fats/ cholesterol - Lowest SA:Vol ratio -low in protein, phospholipids, free cholesterol and cholesterol esters - high in TAGs
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Term
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Definition
-Mainly cholesterol esters
-Almost equal portions (~20) protein and phospholipids - Almost equal portions (~10) free cholesterol and TAGs *Uptake in peripheral tissues by receptor mediated endocytosis
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Term
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Definition
-Mainly TAGs (50%) -Low levels of free cholesterol, protein, and cholesterol esters (7,10,12) -~20% phospholipids |
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Term
| Where does cholesterol synthesis occur? |
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Definition
First half is in cytosol Second part (once it is large and hydrophobic) moves to ER
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Term
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Definition
-Mostly protein -~25% phospholipids 15% cholesterol esters -Hardly any TAGs or free cholesterol *Get transported back to liver
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Term
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Definition
-LDLs and VLDLs -Binds to LDL receptor on peripheral tissues and delivers cholesterol (from liver) |
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Term
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Definition
-Activates lipoprotein lipase in Chylomicrons, VLDL, and HDL -Leads to release of TAGs in peripheral tissue
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Term
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Definition
HDL Activates LCAT to send HDL to liver
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Term
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Definition
-Released from liver into blood -Enters peripheral tissue via binding of Apo B100 to receptors on the tissue -Remnants of VLDL (IDL) can 1. Circulate back to liver 2. Become enriched w/ cholesterol esters -> LDL - This LDL can go to liver or to extrahepatic tisue |
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Term
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Definition
-HDL precursors from (liver and intestine) enter extra hepatic tissue via ACAT activation (by contact with membrane)
- From peripheral tissues, HDL is shipped back to the liver |
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Term
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Definition
Defect in LDL receptor that leads to an inability for the cell to take up LDL Since the liver cannot take up the LDL, it synthesizes more cholesterol than needed Extra cholesterol synthesized remains in blood unless taken care of with medicine |
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Term
| Receptor mediated endocytosis |
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Definition
1. ApoB-100 on LDL binds receptor on outside of cell 2. LDL is taken up by cell via endocytosis 3. In endosome, receptor dissociates 4. Lysosome breaks up endosome/ LDL leaving remnants (FAs, AAs, Cholesterol esters, etc) in cell 5. The released cholesterol moves to ER where it signals LDL receptor synthesis 6. LDL receptor then sent to membrane via golgi app *Process is for peripheral tissue uptake of LDL
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Term
| Key regulated step in cholesterol synthesis |
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Definition
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Term
| Inhibition of production of Mevalonate |
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Definition
Glucagon -> decreased CoA -> decreased HMG synthesis High cholesterol down regulates synthesis and transcription (transcription facor cleaved on ER) |
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Term
| What increases mevalonate production? |
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Definition
| Insulin -> increased glucose -> increased A-CoA -> increased synthesis of mevalonate -> (cholesterol) |
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Term
| What decreases cholesterol synthesis after mevalonate step? |
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Definition
-Excess cholesterol increases proteolic cleavage of HMG-CoA reductase -> change in transcription factors (down regulates) |
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Term
| What increases storage of cholesterol? |
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Definition
| Extra cholesterol stimulates ACAT which esterifies cholesterol and stores |
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Term
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Definition
Competative inhibiters of HMG-reductase Derived from fungi Reduce cholesterol synthesis but do NOT reduce cholesterol in diet |
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Term
| Transamination reaction carriers |
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Definition
NH4 transfer from AAs to carriers (α-keto acids) α-ketoglutarate pyruvate oxaloacetate |
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Term
Ingestion of proteins -> excretion |
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Definition
1. AA exchanges its amino for keto group of carrier 2. New amine formed donates the amino group to form NH4, urea, or ureic acid outside of liver *Look at outline for more information* |
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Term
| Three key amine acceptors/ donors |
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Definition
α-ketoglutarate -> glutamate pyruvate -> alanine oxaloacetate -> spartic acid |
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Term
| Alpha-ketoglutarate structure |
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Definition
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Term
| Transaminase reaction mechanism |
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Definition
| Ping-pong mechanism (double displacement) |
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Term
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Definition
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Term
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Definition
-Coenzyme used for AA catabolism -Initially attached to protein -Acts as a schiff base -Can cycle between being on or off
-Covalent and weak bonds keep it on protein -Helps stabilize carbanion into Quinoid intermediate |
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Term
| Aspartate- arginosuccinate shunt |
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Definition
Aspartate from TCA cycle and Citruline from urea cycle |
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Term
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Definition
-Decarboxylation yeilds an amine and pyridoxal phosphate in aldimine form -Racemization converts from L to D or D to L stereoisomer |
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Term
NH4 collection in hepatocytes using glutamate |
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Definition
-Glutamate oxidized to NH2 form by NAD(P) -NH2 form is hyrdated (by H2O) -> alpha-ketoglutarate and NH4 *NH4 is used in urea cycle *Unique that it can use NAD or NADP "Oxidative deamination"
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Term
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Definition
L-glutamate +ATP + glutamine synthetase -> γ-glutamyl phosphate γ-glutamyl phosphate + NH4 + glutamine synthetase -> L-glutamine +Pi *Transport of L-glutamine from periphery to liver L-glutamine +H2O + Glutaminase -> L-glutamate
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Term
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Definition
1. Glucose in blood -> Pyruvate 2. Pyruvate +Glutamate + alanine transferase -> alanine + α-ketoglutarate in blood 3. Alanine moves to liver 4. Alanine + α-ketoglutarate in liver -> Pyruvate + glutamate *Pyruvate -> glucose via gluconeogenesis, cycle repeat *Glutamate -> NH4 -> Urea cycle |
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Term
| Point of regulation in urea cycle |
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Definition
| Carbamoyl phosphate formation |
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Term
| Where do the carbon groups and amino group in urea come from? |
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Definition
1st NH4 from glutamate ->carbomyl phosphate C from HCO3 -> carbomyl phosphate 2nd amino group from aspartate |
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Term
| Carbomyl phosphate formation |
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Definition
1. NH4 from glutamate or glutamine + HCO3- +2 ATP --> Carbomyl phosphate + 2Pi |
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Term
| Carbomyl phosphate -> Citrulline |
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Definition
1. Carbomyl phosphate +ornithine +transcarbamylase -> Citruline + Pi
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Term
| Citruline -> Arginosuccinate |
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Definition
1. Citrulene +ATP + argininosuccinate synthetase -> [Citrullyl-AMP intermediate] + Pi 2.+ Aspartate ->Argininosuccinate + AMP
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Term
| Argininosuccinate -> arginine |
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Definition
Argininosuccinate+ argininosuccinase -> Arginine AND Fumarate *Fumarate -> TCA cycle
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Term
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Definition
--> Urea AND ornithine *Argininase requires H2O |
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Term
| Which products travel between mitochondria and the cytosol? Which Direction? |
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Definition
1. Cirtuline moves from mitoto cytosol 2. Ornithine moves from cytosol into mitochondria
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Term
| Energetics of aspartate-arginosuccinate shunt |
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Definition
4 ATP used per urea made 2 in CPS-I 2 in arg-suc synthetase *Fumarate -> Malate -> TCA produces NADH (=2.5) therefore net ATP use is 1.5 ATP used/ urea made |
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