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In which cellular compartment does the de novo synthesis of fatty acids (lipogenesis) primarily occur?
The cytosol
What is the immediate substrate for the de novo synthesis of fatty acids?
Acetyl-CoA
What is the primary end product of the fatty acid synthase system in humans?
Free palmitate
Which enzyme catalyzes the conversion of acetyl-CoA to malonyl-CoA?
Acetyl-CoA carboxylase
The conversion of acetyl-CoA to malonyl-CoA requires which vitamin as a cofactor?
Biotin
Name the two reductive steps in fatty acid synthesis that require NADPH as a cofactor.
Reduction of the 3-ketoacyl group and reduction of the 2,3-unsaturated acyl group
What molecule serves as the source of carbon dioxide for the carboxylation of acetyl-CoA?
Bicarbonate (HCO3−)
The fatty acid synthase complex in mammals exists as a dimer of two identical _____.
Polypeptide chains
In the fatty acid synthase complex, which protein contains pantothenic acid as 4'-phosphopantetheine?
Acyl carrier protein (ACP)
Which enzyme activity in the fatty acid synthase complex is responsible for liberating the final palmitate molecule?
Thioesterase
What are the two main pathways that provide NADPH for lipogenesis in the cytosol?
The pentose phosphate pathway and the malic enzyme reaction
Acetyl-CoA carboxylase is allosterically activated by _____.
Citrate
Which molecule acts as a feedback inhibitor of acetyl-CoA carboxylase?
Long-chain acyl-CoA (e.g., palmitoyl-CoA)
How does insulin affect the activity of acetyl-CoA carboxylase?
It promotes dephosphorylation, activating the enzyme
Glucagon and epinephrine inhibit lipogenesis by promoting the _____ of acetyl-CoA carboxylase.
Phosphorylation
In the presence of high AMP, which kinase phosphorylates and inactivates acetyl-CoA carboxylase?
AMP-activated protein kinase (AMPK)
Where does the elongation of existing fatty acid chains primarily occur?
The endoplasmic reticulum (microsomal system)
Fatty acids must be converted to an active intermediate before catabolism. What is this intermediate called?
Acyl-CoA
Which enzyme catalyzes the activation of a fatty acid to acyl-CoA, requiring ATP?
Acyl-CoA synthetase (thiokinase)
What is the primary site for β-oxidation of fatty acids?
Mitochondria
Which molecule transports long-chain acyl-CoA across the inner mitochondrial membrane?
Carnitine
Which enzyme is the gateway for fatty acid entry into mitochondria?
Carnitine palmitoyltransferase-I (CPT-I)
Which intermediate of lipogenesis inhibits CPT-I?
Malonyl-CoA
Each cycle of β-oxidation removes how many carbon atoms?
Two carbons (as acetyl-CoA)
Identify the four steps of β-oxidation.
Dehydrogenation (FAD), hydration, dehydrogenation (NAD+), thiolysis
What is the net ATP yield from complete oxidation of palmitate (C16)?
129 ATP
β-oxidation of odd-chain fatty acids produces acetyl-CoA and _____.
Propionyl-CoA
Why is propionyl-CoA glucogenic?
It is converted to succinyl-CoA
Where does oxidation of very-long-chain fatty acids begin?
Peroxisomes
Under what condition does the liver produce ketone bodies?
High fatty acid oxidation (starvation or diabetes)
Name the three ketone bodies.
Acetoacetate, D-3-hydroxybutyrate, acetone
Which enzyme is rate-limiting in ketogenesis?
HMG-CoA synthase
Ketone bodies are used by _____.
Extrahepatic tissues
Which enzyme required for ketone use is absent in liver?
Succinyl-CoA-acetoacetate CoA transferase (thiophorase)
High ketone bodies in blood is called _____.
Ketonemia
Δ9 desaturase produces what type of fatty acids?
Monounsaturated fatty acids
Why are linoleic and α-linolenic acids essential?
Humans cannot introduce double bonds beyond Δ9
Which C20 fatty acid is precursor for eicosanoids?
Arachidonic acid
Why is cyclooxygenase called a suicide enzyme?
It undergoes self-catalyzed destruction
How do NSAIDs reduce inflammation?
They inhibit COX and block prostaglandin synthesis
Leukotrienes are formed via which pathway?
Lipoxygenase pathway
Function of thromboxane A2?
Vasoconstriction and platelet aggregation
Function of prostacyclin (PGI2)?
Inhibits platelet aggregation
Common precursor of TAGs and phosphoglycerols?
Phosphatidate
Intestinal TAG synthesis starts from _____.
2-monoacylglycerol
Which phospholipid deficiency causes neonatal respiratory distress?
Dipalmitoyl lecithin
All sphingolipids derive from _____.
Ceramide
Ceramide is formed from serine and _____.
Palmitoyl-CoA
Tay-Sachs disease enzyme deficiency?
Hexosaminidase A
Gaucher disease accumulates _____.
Glucosylceramide
Four major plasma lipoproteins?
Chylomicrons, VLDL, LDL, HDL
Which transports dietary TAGs?
Chylomicrons
Which transports endogenous TAGs?
VLDL
Which mediates reverse cholesterol transport?
HDL
Main apoprotein of LDL?
Apo B-100
Cofactor for LPL?
Apo C-II
LPL is located in _____.
Blood capillaries
Chylomicron remnants are taken up via _____.
Apo E receptor
Which enzyme esterifies cholesterol in HDL?
LCAT
Rate-limiting enzyme of lipolysis?
Hormone-sensitive lipase (HSL)
Effect of insulin on HSL?
Inhibits via dephosphorylation
Brown fat uncoupling protein?
Thermogenin
Precursor of LDL?
VLDL
Deficiency causing fatty liver due to impaired VLDL?
Choline
High LDL leads to _____.
Atherosclerosis
Enzyme converting remnants to denser particles?
Hepatic lipase
SR-B1 function?
Uptake of cholesteryl esters from HDL
C2 donor in fatty acid synthesis?
Malonyl-CoA
Signal that inhibits fatty acid oxidation?
Malonyl-CoA
Excess liver fat condition?
Fatty liver (NAFLD)
What happens to CO2 in malonyl-CoA during synthesis?
It is released
Effect of fasting on lipolysis?
Increases lipolysis
Apolipoprotein unique to chylomicrons?
Apo B-48
FFA transport protein in blood?
Albumin
Fate of glycerol from adipose tissue?
Goes to liver
Acetoacetate converts to _____.
Acetone
Source of acetyl-CoA for lipogenesis?
Glycolysis
Cytosolic enzyme producing acetyl-CoA from citrate?
ATP-citrate lyase
α-linolenic acid belongs to which family?
Omega-3
EFA deficiency leads to accumulation of _____.
Mead acid
Enzyme converting arachidonate to PGH2?
Prostaglandin H synthase
Function of LTB4?
Chemotaxis
Ether phospholipids class?
Plasmalogens
Ceramide + phosphatidylcholine forms _____.
Sphingomyelin
Active sulfate donor?
PAPS
Niemann-Pick disease deficiency?
Sphingomyelinase
Krabbe disease deficiency?
β-galactosidase
Hormone regulating appetite and FA oxidation?
Leptin
Ketosis in cattle occurs when?
High glucose demand + low intake
Ethanol metabolism converts pyruvate to _____.
Lactate
Alcohol causes fatty liver because _____.
High NADH inhibits β-oxidation
LCAT activator?
Apo A-I
Function of carnitine translocase?
Exchange acylcarnitine/carnitine
Hypoglycin inhibits _____.
Acyl-CoA dehydrogenases
Refsum disease involves _____.
Phytanic acid
Zellweger syndrome lacks _____.
Peroxisomes
Thiolase function in β-oxidation?
Cleaves 3-ketoacyl-CoA
First step enzyme in TAG synthesis?
Glycerol-3-phosphate acyltransferase
Second messenger for lipolysis?
cAMP
Glucocorticoid effect on lipolysis?
Permissive effect