55. Biochemistry - Lipid Metabolism II Beta Oxidation

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Questions and Answers

What is the enzyme responsible for phosphorylating glycerol in the liver during TAG synthesis?

  • Fatty acyl-CoA synthetase
  • Phosphatidate phosphatase
  • Glycerol kinase (correct)
  • Glycerol-3-P acyltransferase

Which molecule is produced when acyl group from FA-CoA is transferred to 2-MAG during TAG synthesis in intestinal cells?

  • Triacylglycerol
  • Phosphatidic acid
  • Lysophosphatidic acid
  • 1,2-diacylglycerol (correct)

In adipocytes, how is glycerol-3-P primarily obtained for TAG synthesis?

  • From the hydrolysis of phosphatidic acid
  • From acetyl-CoA synthesis
  • By direct phosphorylation of glycerol
  • By reduction of dihydroxyacetone phosphate (correct)

What role does insulin play in storing fatty acids within adipocytes?

<p>It promotes the transfer of fatty acids from lipoprotein carriers (C)</p> Signup and view all the answers

Which of the following statements about glycerol kinase in adipose tissue is correct?

<p>It is not expressed in adipose tissue. (A)</p> Signup and view all the answers

What is the final product of the TAG synthesis pathway in hepatocytes?

<p>Triacylglycerol (D)</p> Signup and view all the answers

What immediately follows the hydrolysis of phosphatidic acid during TAG synthesis in hepatocytes?

<p>Transfer of acyl units to DAG (A)</p> Signup and view all the answers

What is the total amount of ATP yielded from the complete oxidation of palmitate to CO2 and H2O?

<p>106 ATP (D)</p> Signup and view all the answers

Which enzyme is responsible for the carboxylation of propionyl CoA in the odd-chain fatty acid oxidation pathway?

<p>Propionyl CoA carboxylase (A)</p> Signup and view all the answers

What is the role of CoA in each round of b-oxidation?

<p>It is consumed and aids in the breakdown of acyl chains. (B)</p> Signup and view all the answers

In palmitoyl-CoA oxidation, what is produced alongside Acetyl CoA in the final round of b-oxidation?

<p>Propionyl CoA (B)</p> Signup and view all the answers

How many moles of ATP are generated per Acetyl CoA burned to CO2 and H2O during the TCA cycle?

<p>10 ATP (B)</p> Signup and view all the answers

What is the primary function of ATGL in adipocytes?

<p>Hydrolyzes triacylglycerol only (D)</p> Signup and view all the answers

Which form of perilipin protects lipid droplets from lipases in adipocytes?

<p>Non-phosphorylated form (B)</p> Signup and view all the answers

What initiates the phosphorylation of perilipin in adipocytes?

<p>Hormone binding to G-protein coupled receptors (D)</p> Signup and view all the answers

What effect does insulin have on TAG lipolysis?

<p>Inhibits TAG lipolysis (B)</p> Signup and view all the answers

Which lipase enzyme is considered rate-limiting for TAG mobilization?

<p>Adipocyte TAG lipase (ATGL) (D)</p> Signup and view all the answers

Which of the following stimulates lipolysis by increasing cAMP levels?

<p>Epinephrine (D)</p> Signup and view all the answers

What is the role of protein kinase A (PKA) in TAG hydrolysis?

<p>It phosphorylates perilipin and hormone-sensitive lipase (D)</p> Signup and view all the answers

Which hormone directly lowers the rate of TAG lipolysis?

<p>Insulin (A)</p> Signup and view all the answers

Which of the following accurately describes the function of perilipin once phosphorylated?

<p>Changes conformation to expose binding sites for lipases (B)</p> Signup and view all the answers

What is the function of Carnitine acyltransferase I (CAT1)?

<p>Transfers long chain fatty acids from CoA to carnitine. (C)</p> Signup and view all the answers

How are very long chain fatty acids (VLCFA) primarily degraded?

<p>Inside peroxisomes until they are reduced to long chain fatty acids. (B)</p> Signup and view all the answers

Which statement about short chain fatty acids (SCFA) is correct?

<p>They do not require a carrier for transport in blood. (A)</p> Signup and view all the answers

What inhibits the enzyme Carnitine acyltransferase I?

<p>Malonyl-CoA (D)</p> Signup and view all the answers

What role do acyl-carnitine/carnitine transporters play in fatty acid metabolism?

<p>They transport fatty acyl-carnitines into the mitochondrial matrix. (C)</p> Signup and view all the answers

What is a distinguishing feature of medium chain fatty acids (MCFA)?

<p>They bind to albumin for transport in the bloodstream. (B)</p> Signup and view all the answers

Which step in the mitochondrial beta-oxidation pathway is considered rate-limiting?

<p>The transfer of fatty acyl-CoA to carnitine. (D)</p> Signup and view all the answers

Which fatty acid length requires the most complex transport mechanism into the mitochondria?

<p>Long chain fatty acids (B)</p> Signup and view all the answers

What describes the overall process of fatty acid beta-oxidation?

<p>It generates acetyl-CoA from saturated fatty acyl-CoA molecules. (C)</p> Signup and view all the answers

What distinguishes saturated fatty acyl-CoA degradation during beta-oxidation?

<p>It is enzymatically facilitated through three sequential steps. (B)</p> Signup and view all the answers

What role does acyl-CoA dehydrogenase play in the metabolism of fatty acids?

<p>Catalyzes the introduction of a trans double bond between carbons 2 and 3 (D)</p> Signup and view all the answers

Which type of dehydrogenase is specifically involved in the oxidation of long-chain fatty acids?

<p>LCAD (D)</p> Signup and view all the answers

What is the immediate product of the hydration step in fatty acid oxidation?

<p>L stereoisomer of a hydroxyl intermediate (B)</p> Signup and view all the answers

What is the primary role of β-hydroxyacyl-CoA dehydrogenase in the fatty acid oxidation pathway?

<p>Oxidizing alcohols to ketones (C)</p> Signup and view all the answers

How does the fatty acid chain transfer occur in the β-oxidation process?

<p>Via thiolysis catalyzed by acyl-CoA acetyltransferase (C)</p> Signup and view all the answers

What results from the recursive nature of the β-oxidation pathway?

<p>Releasing acetyl-CoA and shortening the fatty acid chain by 2 carbons (C)</p> Signup and view all the answers

Which statement correctly describes the relationship between β-oxidation and oxidative phosphorylation?

<p>Interference in oxidative phosphorylation inhibits β-oxidation (B)</p> Signup and view all the answers

What type of isomers can act as substrates in the process described?

<p>Only L-isomers of hydroxyacyl CoA (A)</p> Signup and view all the answers

Which of the following molecules is generated during the dehydrogenation of the alcohol step?

<p>NADH (A)</p> Signup and view all the answers

Flashcards

TAG synthesis in liver

Liver synthesizes TAGs from glycerol and fatty acids. It uses glycerol kinase to directly phosphorylate glycerol and acyltransferases to assemble the TAG molecule.

TAG synthesis in intestines

Dietary TAGs are broken down, absorbed, and reassembled in enterocytes. Fatty acids are attached to CoA, then transferred to 2-monoacylglycerol to form TAGs.

Glycerol kinase

An enzyme that phosphorylates glycerol, crucial for TAG synthesis in liver.

TAG synthesis in adipocytes

Adipocytes synthesize TAG from fatty acids and glycerol-3-phosphate, predominantly from glucose metabolism.

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Insulin's role in adipocyte TAG synthesis

Insulin promotes fatty acid uptake and glycerol-3-phosphate production in adipocytes, enhancing TAG synthesis.

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Chylomicrons

Amphiphilic particles transporting newly synthesized dietary TAGs in the bloodstream.

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VLDL

Liver-derived TAGs are packaged into VLDL for transport to other tissues.

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TAG Mobilization

The process of breaking down stored triglycerides (TAGs) into fatty acids and glycerol to be used for energy.

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Lipolysis

The breakdown of triglycerides (TAGs) into fatty acids and glycerol.

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ATGL (Adipocyte TAG Lipase)

Rate-limiting enzyme in TAG mobilization; hydrolyzes TAGs only.

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HSL (Hormone-Sensitive Lipase)

Hydrolyzes both TAGs and diacylglycerols (DAGs); its activity is regulated by hormones.

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Perilipin

A protein coating lipid droplets in adipocytes; regulates access of lipases to TAGs.

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Perilipin Phosphorylation

Phosphorylation of perilipin exposes sites in lipid droplet coating, allowing lipases to access TAGs.

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Epinephrine/Glucagon

Hormones that stimulate lipolysis by increasing cAMP and activating PKA.

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Insulin's Role in Lipolysis

Inhibits TAG lipolysis by downregulating ATGL and dephosphorylating HSL & perilipin

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White Adipose Tissue

Body tissue that serves as a major storage site of triglycerides.

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SCFA transport

Short-chain fatty acids (SCFA) are transported in the blood without a carrier.

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MCFA transport

Medium-chain fatty acids (MCFA) use albumin for transport in blood.

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LCFA transport

Long-chain fatty acids (LCFA) are transported bound to the protein albumin.

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Carnitine shuttle

LCFAs use the carnitine shuttle to cross the mitochondrial inner membrane.

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CAT1 (CPT1)

Enzyme that transfers an LCFA from CoA to carnitine (rate-limiting step for b-oxidation).

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CAT2 (CPT2)

Enzyme that catalyzes FA transfer to CoA inside the mitochondria.

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Fatty acid oxidation steps

Saturated fatty acyl-CoA are broken down into acetyl-CoA, with oxidation from acyl end to methyl end.

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VLCFA Degradation

Very long chain fatty acids (VLCFA) are broken down in peroxisomes before entering the mitochondria.

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Rate-limiting step

The slowest step in a metabolic pathway

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Malonyl-CoA Inhibition

Malonyl-CoA inhibits CAT1.

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B-oxidation step 1 product

Produces 1 FADH2 molecule during the first step of fatty acid breakdown.

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B-oxidation step 3 product

Yields 1 NADH molecule in the third step of fatty acid breakdown.

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Palmitoyl-CoA oxidation final product

Yields 8 acetyl-CoAs, along with other breakdown products, following complete oxidation of palmitoyl-CoA.

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Odd-chain fatty acid cleavage products

Results in acetyl-CoA and propionyl-CoA when undergoing b-oxidation in step 4.

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Propionyl-CoA conversion

Converts propionyl-CoA to succinyl-CoA in three steps, crucial for entering the TCA cycle.

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Dehydrogenation of Alkane to Alkene

The first step in Beta-oxidation, where an alkane is converted to an alkene, introducing a double bond between carbons 2 and 3. It's catalyzed by acyl-CoA dehydrogenase.

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Enoyl-CoA Hydratase

Enzyme catalyzing the addition of water to the alkene double bond in b-oxidation, forming a hydroxyl intermediate.

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Beta-hydroxyacyl-CoA dehydrogenase

Enzyme catalyzing the oxidation of the alcohol to a ketone, producing NADH.

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Acyl-CoA acetyltransferase/b-ketothiolase

Enzyme that cleaves the fatty acyl chain, releasing acetyl-CoA and shortening the chain for subsequent rounds of b-oxidation.

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Beta-oxidation Recursion

The beta-oxidation process repeats, removing two-carbon fragments at each cycle, until the entire fatty acid is oxidized.

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Fatty Acid Saturation

The beta-oxidation pathway is efficient for fully saturated fatty acids with an even number of carbons.

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Oxidative Phosphorylation

Beta-oxidation is linked to oxidative phosphorylation, meaning the electron transport chain is essential for the process.

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LCAD (long-chain fatty acyl-CoA dehydrogenase)

An isoform of Acyl-CoA dehydrogenase responsible for b-oxidation of long-chain fatty acids.

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MCAD (medium-chain fatty acyl-CoA dehydrogenase)

An isoform of Acyl-CoA dehydrogenase responsible for b-oxidation of medium-chain fatty acids.

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SCAD (short-chain fatty acyl-CoA dehydrogenase)

An isoform of Acyl-CoA dehydrogenase responsible for b-oxidation of short-chain fatty acids.

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Study Notes

Triacylglycerol Metabolism & Fatty Acid Oxidation

  • Learning Objectives:
    • Identify 3 sites of triacylglycerol synthesis and their differences.
    • Explain glucagon, epinephrine, and insulin's effects on TAG mobilization.
    • Detail the mitochondrial pathway for fatty acid oxidation (FA entry, β-oxidation steps, propionyl-CoA catabolism).
    • Recognize enzymes for oxidizing unsaturated fatty acids and why they yield less energy.
    • Compare/contrast fatty acid oxidation in peroxisomes.
    • Define metabolic syndromes: carnitine deficiency, MCAD deficiency, X-ALD, and Zellweger/Refsum disease.

Triacylglycerol (TAG) Synthesis

  • Principal sites: Small intestine (enterocytes), liver (hepatocytes), and adipose tissue (adipocytes).
  • Intestinal synthesis: Part of dietary lipid digestion, converting excess hydrocarbons into stored energy.
  • Hepatic synthesis: De novo fatty acid synthesis from acetyl-CoA. Glycerol-3-P is phosphorylated from glycerol.
  • Mechanism: Acyl groups are attached to glycerol-3-P, creating DAG, then TAG. This process forms chylomicrons.
  • Adipocyte synthesis: Insulin promotes FA and glycerol-3-P uptake; TAG synthesis occurs within adipocytes.

TAG Mobilization

  • Epinephrine and glucagon: Stimulate lipolysis (breakdown of TAG).
  • Insulin: Inhibits lipolysis by decreasing the activity of key lipase enzymes (ATGL, HSL, MGL).
  • Hormone-linked function of perilipin: Perilipin coats lipid droplets in adipocytes, protecting them from lipases.

Mitochondrial Fatty Acid Oxidation

  • FA entry: Fatty acids enter the mitochondrial matrix via carnitine transport.
  • β-oxidation pathway: A four-step cycle that removes 2-carbon fragments as acetyl-CoA, producing FADH2 and NADH.
  • Unsaturated fatty acids: Require additional enzymes (isomerases) to process different double-bond configurations.
  • Propionyl-CoA catabolism: A distinct pathway for odd-numbered fatty acids.
  • Energetics: Oxidizing unsaturated fatty acids results in less energy release than saturated fatty acids.

Peroxisomal Pathway

  • Pathway: An alternative for fatty acid oxidation, particularly for very long-chain fatty acids (VLCFAs).
  • VLCFA oxidation: Peroxisomes convert VLCFAs to shorter-chain fatty acids, before their transfer to the mitochondria.

Metabolic Disorders

  • Carnitine deficiency: Defect in transporting fatty acids into mitochondria.
  • MCAD deficiency: Inability to oxidize medium-chain fatty acids, leading to possible acidosis & hypoglycemia.
  • X-ALD: Defect in VLCFA transport in peroxisomes, resulting in build-up of VLCFAs & damage to CNS and adrenal glands.
  • Zellweger syndrome/Refsum disease: Defects in peroxisomal biogenesis result in accumulation of phytanic acid & harmful effects on the nervous system.

Fatty Acid β-oxidation

  • Four steps: Dehydrogenation, hydration, dehydrogenation, and thiolysis.
  • Yield calculations: The breakdown of one palmitic acid (saturated) yields 106 ATP.
  • Odd-chain fatty acids: Require additional enzymes to process the propionyl-CoA produced.
  • Unsaturated fatty acids: Must be isomerized to a form usable by the β-oxidation enzymes.

Energy Yield from Beta Oxidation

  • Saturated fatty acids yield 1 FADH2 and 1 NADH per cycle, along with 1 acetyl CoA, producing the needed energy.
  • Each round of β-oxidation consumes 1 water and 1 coenzyme A.

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