Lipid Synthesis and Storage Flashcards
Rate-limiting enzyme of fatty acid biosynthesis
Acetyl CoA carboxylase (Activated by Insulin because Fat deposition is favored)
The biotin-requiring enzymes
The 3 “P-A-P” carboxylases: Pyruvate carboxylase (Pyruvate to OAA in Gluconeo), Acetyl CoA carboxylase (Acetyl CoA to Malonyl CoA in Fatty Acid Synthesis), and Propionyl-CoA Carboxylase (odd chain fat oxidation)
The thiamine-requiring enzymes
The 4 “A-T-P-B” dehydrogenases: Alpha-ketoglutarate DH (TCA), Transketolase* (PPP pentose interconversion), Pyruvate DH (Pyruvate to Acetyl CoA), Branched-chain Ketoacid DH (“IVL” to Acetyl CoA and Propionyl CoA)
Another name for fatty acid synthase, with the product being the only fatty acid that humans can synthesize de novo
Palmitate synthase (Palmitate)
Required to reduce the acetyl groups added to the elongating chain in fatty acid synthesis
NADPH
Number of acetyl CoA required for synthesis of palmitate
8
Cytochrome involved in the desaturation reactions in fatty acid synthesis
Cyt b5
In fatty acid synthesis, double bonds can only be introduced up to what carbon position?
Carbon position 9 (up to 8 double bonds)
Components of TAGs
3 fatty acids + glycerol
Tissues capable of synthesizing TAG as the storage form of fatty acids
Liver and Adipose tissue
2 sources of glycerol-3P for TAG synthesis
Reduction of DHAP from glycolysis (G3P DH) in adipose (this is the only source for adipose) and liver; phosphorylation of the free glycerol released from reabsorbed VLDL (Glycerol kinase) in LIVER ONLY
Diacylglycerol, inositol 1,4,5-triphosphate, and arachidonic acid are second messengers that are (biomolecule class)
Glycerophospholipids (differing from Glycerol by replacing one FA with 3P-Inositol)
Glycerophospholipid functioning as lung surfactant
Phosphatidylcholine
Lightest lipoprotein
Chylomicrons < VLDL < IDL < LDL < HDL
Apoproteins of Chylomicrons
apoB-48, apoC-II, apoE
Apoproteins of VLDLs
apoB-100, apoC-II, apoE
Only apoprotein of LDL
apoB-100
Apoprotein of HDL
apoA-1 (responsible from cholesterol recovery from fatty streaks in the blood vessels)
Induced by insulin and transported to the luminal surface of capillary endothelium, hydrolyzes the fatty acids from TAGs carried by chylomicrons and VLDL
Lipoprotein Lipase
Apoprotein that activates LPL
apoC-II
The thoracic duct joins what vessel?
left subclavian vein
Enzyme exclusively in the liver, allows liver to have an instant supply of glycerol unlike in adipose where glycerol is sourced from DHAP
glycerol kinase sequesters glycerol as LPL breaks down Chylomicron and VLDL TAGs
apoC-II and apoE apoproteins are obtained by Chylomicrons and VLDLs from?
HDLs circulating in the blood
Fate of the VLDL remnant, IDL
Some are picked up by hepatocytes through their apoE receptor for recycling, some acquire cholesterol esters from HDL particles in the blood to become LDL
Normal role of LDL
Deliver cholesterol to tissues needing them for biosynthesis of bile acids and salts, steroids, etc
Aside from de novo synthesis, hepatocytes can obtain cholesterol from/by
Endocytosis of LDL and Chylomicron remnants with residual dietary cholesterol, Transfer of cholesterol from HDL (via SR-B1 receptor)
High cholesterol in hepatocytes inhibits further accumulation by reducing gene expression of
HMG-CoA reductase, and the LDL and SR-B1 receptors
Protein that coats the “pit” (invagination) for endocytosis of LDL
clathrin
Enzyme in the blood activated by apoA-1. It adds a fatty acid ti cholesterol to produce cholesterol esters that dissolve in the HDL core
Lecithin-cholesterol acyltransferase (LCAT)
Protein that transfers HDLs’ cholesterol esters to IDLs, eventually converting the latter to LDLs
Cholesterol ester transfer protein (CETP)
Receptors for HDLs that are highly expressed in tissues needing the cholesterol scavenged by HDLs along the way
Scavenger receptors, SR-B1, are highly abundant in hepatocytes and the steroidogenic tissues (ovaries, testes, adrenals)
Endothelial damage, high LDL, low HDL, predisposes to what clinical condition
Atherosclerosis
Special type of macrophages present in atherosclerotic plaques that takes up oxidized LDL
Foam cells
Vitamin that exhibits antioxidant property in lipid phase, preventing peroxidation of membrane lipids
Vit E
Rare genetic absence of LPL resulting in excess TAGs in blood and its deposition as xanthomas
Familial lipoprotein lipase deficiency (Type 1 Primary Hyperlipidemia). Symptoms include red-orange eruptive xanthomas, fatty liver, acute pancreatitis, abdominal pain after fatty meal
Most common type of hyperlipidemia
Type V
Lipid abnormality commonly found in diabetics
High triglycerides, low HDL
Lipid abnormality in diabetics (high triglycerides) is caused by
Abnormally low levels of lipoprotein lipase (LPL), inability to degrade serum triglycerides in lipoproteins to facilitate uptake of FA into adipocytes
Deficiency in Type Iia Hypercholesterolemia, characterized by elevated LDL cholesterol, increased risk for atherosclerosis, and CAD
LDL Receptor Deficiency. Cholesterol deposits are also seen as xanthomas of the Achilles tendon, subcutaneous tuberous xanthomas over the elbows, xanthelasma (lipid in eyelid), and corneal arcus (vs arcus senilis)
Hypolipidemia caused by low to absent serum apoB-100 and apoB-48 (main deficiency). Serum triglycerides may be near zero, and cholesterol extremely low.
Abetalipoproteinemia. Steatorrhea, cerebellar ataxia, pigmentary degeneration in the retina, acanthocytes (“thorny” appearing erythrocytes), possible loss of night vision, is due to low chylomicron levels and fat accumulation in intestinal enterocytes and hepatocytes. Essential fatty acids (linoleic acid) and Vit A and E not well absorbed
Rate-limiting enzyme in cholesterol synthesis
3-Hydroxy-3-methylglutaryl (HMG)-CoA reductase; Activated by Insulin, Inhibited by Glucagon
Product of HMG-CoA
Mevalonate (catalyzed by HMG-CoA reductase)
Drug inhibitors of HMG-CoA reductase
Statins inhibit de novo cholesterol synthesis. Decreased hepatocyte cholesterol level will increase LDL receptor expression, more “clearing up” of the blood of LDL
Drugs that increase elimination of bile salts, forcing liver to increase synthesis of cholesterol and to increase LDL receptor expression
Cholestyramine is used in the treatment of hypercholesterolemia
An intermediate of the cholesterol synthesis pathway used for CoQ synthesis (for ETC), Dolichol pyrophosphate synthesis (cofactor in N-glycosylation in ER), and prenylation of proteins
Farnesyl pyrophosphate
Side effect of statins caused by decrease in Farnesyl pyrophosphate levels due to decreased HMG-CoA reductase activity
Muscle soreness, pain, weakness, red-brown urine caused by myoglobinuria from damaged muscle cells. Muscle is damaged due to decreased ability to generate ATP due to decreased ETC since Farnesyl pyrophosphate is needed for synthesis of CoQ
