FAs, Lipids, and Cholesterol Flashcards Preview

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Flashcards in FAs, Lipids, and Cholesterol Deck (50)
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End Point of FA Synthesis

Palmitic Acid


Getting Acetyl CoA into Cytosol for FA Synthesis (3 Steps)

ATP binds isocitrate dehydrogenase and inhibits it, causing buildup of citrate
Citrate moved out of mt matrix into cytosol
ATP-citrate lyase acts as opposite of citrate synthase and cleaves it into OAA and Acetyl CoA


Acetyl CoA Carboxylase (2)

Gateway to FA synthesis
Converts Acetyl CoA to Malonyl CoA via carboxylation


Acetyl CoA Carboxylase Regulation

AMP-dependent kinase (AMPK) phosphodeactivates it into inactive dimer under starving/epinephrine conditions, whereas protein phosphatase dephosphoactivates it into active polymer from insulin


Process of FA Synth (7)

Acetyl CoA attaches to cysteine residue of carrier prot
Malonyl CoA attaches to modified pantothenate on that prot
Malonyl decarbox'd, new carbanion attacks acetyl group
Reduction of last carbonyl group via NADPH
Dehydration of new OH/H
Reduction of new double bond via NADPH
Transfers to cysteine residue, new malonyl CoA added to pantothenate, cycled continues to palmitate (16C)


NADPH Production Associated w/ FA Synthesis (2 steps)

Cytosolic NADH-dependent malate dehydrogenase converts OAA to malate. NADP+ dependent malate dehydrogenase converts malate to pyruvate and creates NADPH from it


2 Sources of Glycerol PO4 production in Liver

Dihydroxyacetone P from glycolysis converted via glycerol-P dehydrogenase
Glycerol converted via Glycerol kinase


1 Source of Glycerol P Production in Adipose Tissue

DHAP from glycolysis converted via glycerol-P dehydrogenase


TAG Synthesis (3)

Acyltransferases add to glycerol P twice until its phosphatidic acid
Phosphatase then removes PO4 so its diacylglycerol (DAG)
Acyltransferase then adds acyl so its triacylglycerol (TAG)


Hormone-Sensitive Lipase

Activated by protein kinase from glucagon/epinephrine, breaks down TAGs


Carnitine Shuttle (purpose and mech[2])

To transport LC FA-CoA from cyt to mt matrix without risk of synthesized FAs going right back in to matrix
Fatty acyl CoA transported to IM space, where carnitine palmitoyl-transferase I switches CoA for Carnitine
Then Fatty Acyl Carnitine transported to matrix, where carnitine palmitoyl transferase II switches back to Fatty Acyl CoA


Beta Oxidation Rxns (4)

Oxidation of C2/3 yields double bond and produces FADH2
Hydration of double bond at C3
Oxidation of C3 hydroxyl, yielding NADH
Thiolysis w/ addition of CoA creating Acetyl CoA and Fatty acyl CoA (2Cs shorter)


3 Products from Full Beta Oxidation of Palmitoyl CoA

7 FADH2, 7 NADH, and 8 Acetyl CoA


Beta Oxidation of Odd-Number Chain FAs

Go through separate pathway where coenzyme form of Vit B12 eventually converts Methylmalonyl-CoA to Succinyl CoA for TCA cycle


Ketone Body Synthesis (4)

FA Beta Oxidation yields Acetoacetyl CoA
HMG CoA Synthase adds another acetyl CoA to form HMG CoA
HMG CoA lyase removes acetyl CoA to form acetoacetate
3-Hydroxybutyrate dehydrogenase converts to 3-Hydroxybutarate


Phospholipid Synthesis

CTP activates phosphatidic acid by adding CDP to diacylglycerol, and then an alcohol w/ head group can add


Cleaving Points for the 4 Phospholipases

A1: C1 acyl group
A2: C2 acyl group
C: C3 after the O, before the P
D: C3 polar head group but leaves the P


Phospholipase C Important Mech Involvement

Cleaves Phosphatidyl-inositol 4,5-bisphosphate to IP3 and DAG


Niemann-Pick Disease (3)

Sphingomyelinase deficiency (sphingolipidosis)
Causes buildup of sphingomyelin and prevents ceramide release
Foamy appearing cells containing sphingomyelin under microscope



Ceramide w/ sugar residue



Cerebroside w/ charged COO- on terminal sugar



Cerebroside w/ OSO3- on terminal sugar


Tay-Sachs Disease (4)

Beta-Hexosaminidase A deficiency
Causes accumulation of gangliosides (specifically NANA)
Prevents ceramide release


Gaucher Disease (4)

Beta-glucosidase deficiency
Causes buildup of glucocerebrosides
Prevents ceramide release


Prostaglandin Synthesis (4)

Dietary linoleic acid converted into arachidonic acid, which COX converts to PGG2 w/ 2 O2, and then peroxidase converts into PGH2, which differentiates into the different prostaglandins


2 Fates of Arachidonic Acid

5-Lipoxygenase converts to Leukotrienes
COX-1 or 2 modify to PGG2


2 Prostaglandins and Function

Thromboxane A2 (TXA2) promotes platelet aggregation
Prostacyclin (PGI2) in endothelium of blood vessels, promoting vasodilation


Aspirin Mech (3)

Acetylates serine side chain in COX active site, preventing prostaglandin synthesis
Platelets don't have nuc, so TXA2 inhibition means they're done so blood thinning
Endothelial cells can just degrade COX and make more, so PGI2 still fine


Rate-Limiting "Gateway" into Cholesterol Biosynthesis

HMG CoA reductase converts HMG CoA to mevalonate


Synthesis of Cholesterol Mevalonate->on (7)

6C mevalonate phopho'd twice to form 5-pyrophosphomevalonate
Decarbox'd to isopentenyl pyrophosphate (IPP) (5C)
Isomerized to dimethylallyl pyrophosphate (DPP) (5C)
IPP added to form Geranyl pyrophosphate (10C)
IPP added to form farnesyl pyrophosphate (15C)
2 of those form Squalene (30C)
Then hydroxy added and other modifications to turn it into cholesterol


Stimulation of HMG CoA Reductase Activity (2)

Phosphoprotein phosphatase dephosphoactivates it
SREBP also binds SRE, stimulating transcription of HMG CoA Reductase


Inhibition of HMG CoA Reductase (2)

AMPK phosphodeactivates
Cholesterol inhibits SREBP release from Golgi


Statins Action

Lower cholesterol my inhibiting HMG CoA Reductase


Bile Acid Synthesis

Cholesterol 7-alpha-hydroxylase adds carboxylic acid to cholesterol alkane tail to for cholic acid or chenodeoxycholic acid


Bile Salt Synthesis (2)

Glycine added to cholic acid to make glycocholic acid
Taurine added to chenodeoxycholic acid to make Taurochenodeoxycholic acid


Enterohepatic Circulation

Bile salts/acids sent from liver/gallbladder to intestines and those that aren't excreted are recycled back to liver


Steroid Synthesis (7 different molecules mentioned total)

Cholesterol to pregnenolone to progesterone which differentiates into cortisol, aldosterone, or testosterone (and then estradiol from there)


Congenital Adrenal Hyperplasias (CAH)

Deficiencies in enzymes along the steroid hormone synthesis pathway


General Passage of Cholesterol Through Lipoproteins (5)

Chylomicrons w/ lots of TAGs go from GI to muscles/tissues
Remnants go to liver
Contents repackaged into VLDL w/ some TAGs and cholesterol which goes to tissues
LDL returns to liver w/ just cholesterol and cholesteryl esters
HDL then secreted in bile, takes up cholesterol from peripheral tissues and returns


Lipoprotein w/ Highest TAG component



Lipoprotein w/ Highest Cholesterol Component



Chylomicron Apolipoproteins (3 prots, 5 points)

Apo B-48 added upon nascent in SI
Then C-II and Apo E added from HDL
C-II activates lipoprotein lipase to hydrolyze TAGs to FAs and glycerol in capillaries
Then Apo C-II returned to HDL from remnant
Apo E binds to Rs in liver for endocytosis of the remnant


VLDL and LDL Apolipoproteins (3 prots, 5 points)

Apo B-100 on nascent VLDL in liver
Then Apo C-II and Apo E added from HDL
Apo C-II activates lipoprotein lipase to hydrolyze TAGs to FAs and glycerol in capillaries
Apo C-II and Apo E returned to HDL from LDL (which now has CEs and C almost entirely)
Apo B-100 binds to LDL Rs on extrahepatic/liver tissues and are endocytosed


Cholesteryl Ester Transfer Protein (CETP)

Catalyzes transfer of TAGs to HDL from VLDL and CE from HDL to VLDL


Difference b/w Apo B-100 and Apo B-48

Come off same gene w/ same mRNA, but a cytosine is edited in ssRNA to create a stop codon to make Apo B-48 for chylomicrons


Familial Hypercholesterolemia

Low LDL Rs causes hypercholesterolemia



Gene for LDL R degrading protein on outside of the cell, new even more effective target for inhibition decreasing cholesterol


2 Inhibitory Effects by Cholesterol

Blocks HMG CoA Reductase
Blocks synthesis of LDL Rs


Cholesterol's Contribution to Arterosclerosis (major point and 4 steps)

Individual has to have high cholesterol *AND* unknown susceptibility to oxidative
Endothelium causes/releases oxidative stress
LDLs damaged by it
Macrophages swallow damaged LDLs and become foam cells
Foam cells deposit onto arterial walls causing plaques


HDL Circulation

Released as bile and then has intermediate stages which pick up cholesterol from peripheral tissues and return to liver