Metabolic Functions Quiz
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Questions and Answers

What is the primary function of Acetyl-CoA Carboxylase (ACC1) in fatty acid synthesis?

  • It hydrolyzes palmitoyl-ACP to yield free palmitate.
  • It phosphorylates and activates enzymes involved in oxidative metabolism.
  • It transfers acyl groups to the beta-carbon of Malonyl-CoA.
  • It catalyzes the rate-limiting step in fatty acid synthesis. (correct)

    • Which of the following correctly describes the role of citrate in the regulation of ACC1?

  • It inhibits ACC1 by promoting depolymerization.
  • It acts as a feedforward inhibitor, slowing down synthesis.
  • It activates ACC1 by promoting its polymerization. (correct)
  • It has no significant effect on the activity of ACC1.

    • How do the processes of fatty acid synthesis and beta-oxidation primarily differ?

  • Fatty acid synthesis produces double bonds beyond C9 while beta-oxidation does not.
  • Both processes occur in the mitochondria.
  • Fatty acid synthesis generates NADH while beta-oxidation consumes it.
  • Fatty acid synthesis occurs in the cytoplasm, whereas beta-oxidation occurs in mitochondria and peroxisome. (correct)

    • What role does insulin play in the regulation of ACC1?

    <p>It dephosphorylates and activates ACC1.</p> Signup and view all the answers

    Which statement about essential fatty acids (EFA) is true regarding mammals?

    <p>Mammals cannot introduce double bonds beyond C9, requiring dietary intake.</p> Signup and view all the answers

    Which factor primarily influences appetite regulation in mammals?

    <p>Leptin secretion from adipose tissue</p> Signup and view all the answers

    What is the role of glucagon during fasting?

    <p>Prevents hypoglycemia by stimulating glycogenolysis and gluconeogenesis</p> Signup and view all the answers

    During prolonged fasting, which of the following serves as an alternative energy source for muscles?

    <p>Fatty acids mobilized from adipose tissue</p> Signup and view all the answers

    How does insulin influence metabolism during the postprandial state?

    <p>Promotes glucose uptake and stimulates glycogenesis</p> Signup and view all the answers

    What metabolic process is mainly regulated by the hypothalamus?

    <p>Energy balance and appetite control</p> Signup and view all the answers

    What is the primary function of chylomicrons after food intake?

    <p>Transport lipids to muscle and adipose tissue</p> Signup and view all the answers

    In which condition do skeletal and cardiac muscles primarily utilize fatty acids for energy?

    <p>In the fasting state</p> Signup and view all the answers

    Which statement about the feeding-fasting cycle is accurate?

    <p>Mammals rely on hormonal regulation for metabolic integration.</p> Signup and view all the answers

    Which hormone secreted by the stomach is primarily responsible for stimulating appetite?

    <p>Ghrelin</p> Signup and view all the answers

    What role does glucagon primarily serve in the body?

    <p>Stimulates catabolism and increases blood glucose levels</p> Signup and view all the answers

    Which of the following factors can contribute to obesity?

    <p>Genetics and sedentary lifestyle</p> Signup and view all the answers

    In the context of metabolic effects during fasting, which of the following is promoted by glucagon?

    <p>Glycogenolysis and gluconeogenesis</p> Signup and view all the answers

    What is the primary metabolic function of the liver in relation to blood glucose levels?

    <p>Regulates blood glucose levels and nutrient metabolism</p> Signup and view all the answers

    Which hormone secreted by the small intestine inhibits appetite?

    <p>Peptide YY (PYY)</p> Signup and view all the answers

    Which of the following statements regarding statins and cholesterol synthesis is true?

    <p>Statins inhibit enzymes involved in cholesterol synthesis.</p> Signup and view all the answers

    What detrimental effect can high levels of LDL have on blood vessels?

    <p>Promote the formation of foam cells in arteries</p> Signup and view all the answers

    What is the primary action of NADPH synthesizing genes during metabolism?

    <p>Participate in lipid synthesis</p> Signup and view all the answers

    Which organ is primarily responsible for nutrient absorption and digestion?

    <p>Gastrointestinal tract</p> Signup and view all the answers

    What is a distinguishing characteristic of Type 1 Diabetes?

    <p>Destruction of pancreatic beta-cells</p> Signup and view all the answers

    Which hormone is primarily responsible for stimulating appetite?

    <p>Ghrelin</p> Signup and view all the answers

    What happens to the brain's energy source after several weeks of fasting?

    <p>It adapts to use ketone bodies</p> Signup and view all the answers

    What is the primary method of treating Type 2 Diabetes?

    <p>Lifestyle changes including diet and exercise</p> Signup and view all the answers

    Which condition is characterized by the presence of glucose in the urine?

    <p>Glycosuria</p> Signup and view all the answers

    What is a key metabolic effect of prolonged fasting?

    <p>Mobilization of fatty acids and ketone bodies</p> Signup and view all the answers

    Which hormone is responsible for inhibiting appetite?

    <p>Leptin</p> Signup and view all the answers

    What is a common symptom shared by both types of diabetes?

    <p>Hyperglycemia</p> Signup and view all the answers

    What role do the arcuate nucleus neurons play in appetite regulation?

    <p>They integrate hormonal signals and sensory input</p> Signup and view all the answers

    What is the result of prolonged uncontrolled Type 2 Diabetes?

    <p>It can lead to insulin dependency</p> Signup and view all the answers

    What is the primary energy source for the heart and skeletal muscle during high-energy demand?

    <p>Ketone bodies</p> Signup and view all the answers

    What enzyme catalyzes the rate-limiting step in fatty acid biosynthesis?

    <p>Acetyl-CoA carboxylase</p> Signup and view all the answers

    During prolonged fasting, which organ primarily utilizes ketone bodies as a major energy source?

    <p>Brain</p> Signup and view all the answers

    Which fatty acid is specifically synthesized by mammals and acts as a precursor for longer and shorter fatty acids?

    <p>Palmitic acid</p> Signup and view all the answers

    Which of the following statements regarding the synthesis of ketone bodies is true?

    <p>Acetoacetate can be formed from HMG-CoA.</p> Signup and view all the answers

    In the context of fatty acid biosynthesis, what role does ACP (acyl carrier protein) play?

    <p>It acts as a fatty acid activator.</p> Signup and view all the answers

    What is the product of the spontaneous decarboxylation of acetoacetate?

    <p>Acetone</p> Signup and view all the answers

    Which of the following is NOT a step in the four repeating cycle of fatty acid synthesis?

    <p>Hydrolysis</p> Signup and view all the answers

    Which reaction represents the activation of malonyl-CoA during fatty acid biosynthesis?

    <p>Malonyl-CoA + ACP-SH → Malonyl-ACP</p> Signup and view all the answers

    What is the significance of the 2-carbon increase in the acyl group during fatty acid synthesis?

    <p>It facilitates the attachment of longer fatty acids to acyl carrier proteins.</p> Signup and view all the answers

    Which enzyme is crucial for the elongation of fatty acids during synthesis?

    <p>Elongase</p> Signup and view all the answers

    What is the primary function of palmitoyl-CoA in the regulation of ACC1?

    <p>To inhibit the activity of ACC1 through depolymerization.</p> Signup and view all the answers

    How does the process of fatty acid synthesis primarily differ from beta-oxidation regarding energy consumption?

    <p>Fatty acid synthesis consumes NADPH, whereas beta-oxidation generates NADH and FADH2.</p> Signup and view all the answers

    In which cellular location do fatty acid elongation and desaturation occur?

    <p>Endoplasmic reticulum</p> Signup and view all the answers

    What characterizes the form in which Acetyl-CoA Carboxylase (ACC1) is active?

    <p>Dimerized and dephosphorylated</p> Signup and view all the answers

    Which dietary components are primarily considered essential fatty acids (EFA) for mammals?

    <p>Fatty acids that contain double bonds beyond C9</p> Signup and view all the answers

    Which of the following statements accurately compares the intermediates in fatty acid synthesis and beta-oxidation?

    <p>Fatty acid synthesis and beta-oxidation both use the same intermediates.</p> Signup and view all the answers

    Which phospholipid is known to stabilize membrane curvature?

    <p>Phosphatidylethanolamine</p> Signup and view all the answers

    What is the first step in the synthesis of phosphatidylethanolamine?

    <p>Ethanolamine is phosphorylated by a kinase</p> Signup and view all the answers

    Which phospholipase enzyme hydrolyzes both C1 and C2 ester bonds?

    <p>PLB</p> Signup and view all the answers

    Which class of phospholipids does sphingomyelin belong to?

    <p>Sphingolipids</p> Signup and view all the answers

    Which of the following is predominantly found in biological membranes?

    <p>Phosphatidylcholine</p> Signup and view all the answers

    What is primarily indicated by the presence of phosphatidylserine in the cellular context?

    <p>Signal for macrophages to engulf cells</p> Signup and view all the answers

    What occurs during phospholipid turnover?

    <p>Fatty acids are replaced with new fatty acids</p> Signup and view all the answers

    Which intermediate is formed from triacylglycerol during phosphatidylcholine and phosphatidylethanolamine synthesis?

    <p>Diacylglycerol</p> Signup and view all the answers

    What is the role of phospholipases in lipid metabolism?

    <p>Degrade phospholipids</p> Signup and view all the answers

    Which phospholipase is specifically responsible for hydrolyzing the phosphodiester bond between the glycerol and phosphate?

    <p>PLC</p> Signup and view all the answers

    How does prolonged fasting change the brain's preferred energy source?

    <p>The brain adapts to utilize ketone bodies for energy.</p> Signup and view all the answers

    What is the primary effect of ghrelin on appetite regulation?

    <p>It stimulates food intake by activating AgRP/NPY neurons.</p> Signup and view all the answers

    Which hormone primarily acts to inhibit appetite through its effect on AgRP/NPY neurons?

    <p>Leptin</p> Signup and view all the answers

    Which of the following symptoms occurs due to hyperglycemia in diabetes mellitus?

    <p>Excessive thirst and frequent urination</p> Signup and view all the answers

    What distinguishes Type 1 diabetes from Type 2 diabetes?

    <p>Type 1 diabetes is an autoimmune disease destroying pancreatic cells.</p> Signup and view all the answers

    What is the direct product of the reaction between sphinganine and a long chain fatty acid?

    <p>Ceramide</p> Signup and view all the answers

    Which of the following compounds is formed when ceramide reacts with UDP-galactose?

    <p>Galactocerebroside</p> Signup and view all the answers

    What contributes to Niemann-Pick Syndrome in relation to sphingomyelin?

    <p>Defective sphingomyelinase</p> Signup and view all the answers

    What characterizes sphingomyelin's structure compared to other sphingolipids?

    <p>Is esterified to a phosphate group</p> Signup and view all the answers

    Which of the following reactions does NOT occur during sphingolipid synthesis?

    <p>Ceramide + UDP-galactose → Glucocerebroside</p> Signup and view all the answers

    Which statement correctly describes the end product of sphingomyelin metabolism?

    <p>Involves sphingomyelinase activity</p> Signup and view all the answers

    What is the role of ceramide in the synthesis of glycosphingolipids?

    <p>It reacts with different UDP-sugars</p> Signup and view all the answers

    Which enzyme is responsible for the breakdown of sphingomyelin?

    <p>Sphingomyelinase</p> Signup and view all the answers

    Which of the following correctly describes a key feature of cerebrosides?

    <p>They typically have a monosaccharide as the head group</p> Signup and view all the answers

    What is the first compound formed during sphingosine synthesis?

    <p>Sphinganine</p> Signup and view all the answers

    What is the primary mechanism by which statins lower blood cholesterol levels?

    <p>Inhibiting the activity of HGMR</p> Signup and view all the answers

    Which type of cell transformation results from macrophages accumulating oxidized LDL?

    <p>Lipid-laden macrophages</p> Signup and view all the answers

    Which hormone secreted by the pancreas promotes glucose uptake in muscle tissue?

    <p>Insulin</p> Signup and view all the answers

    What role does the liver play in nutrient metabolism concerning blood glucose levels?

    <p>Regulates blood glucose levels through gluconeogenesis and glycogenolysis</p> Signup and view all the answers

    What is a common characteristic of foam cells within atherosclerotic plaques?

    <p>They contribute to plaque formation and necrosis.</p> Signup and view all the answers

    What is a potential consequence of taking statins without a CoQ supplement?

    <p>Decreased energy production in cells</p> Signup and view all the answers

    Which biochemical process is primarily affected by the action of NADPH synthesizing genes?

    <p>Fatty acid synthesis</p> Signup and view all the answers

    What physiological role does peptide YY (PYY) serve within the gastrointestinal tract?

    <p>Inhibits appetite</p> Signup and view all the answers

    Which organ is crucial for both digestion and the regulation of metabolic activities related to nutrient absorption?

    <p>Gastrointestinal tract</p> Signup and view all the answers

    How do foam cells contribute to atherosclerosis progression?

    <p>By oxidizing LDL and promoting inflammation</p> Signup and view all the answers

    Study Notes

    Role of Skeletal Muscle

    • Skeletal muscle constitutes 50% of body mass and consumes a significant portion of generated energy.
    • Cardiac muscle uses glucose during the fed state and fatty acids during the fasting state.
    • Insulin activates glucose absorption into skeletal and cardiac muscle through GLUT4 translocation.

    Role of Adipose Tissue

    • Adipose tissue stores energy as triglycerides.
    • It secretes leptin, a peptide hormone that promotes satiety (inhibits appetite).

    Role of Brain

    • The brain directs most metabolic processes.
    • The hypothalamus plays a crucial role in energy balance.
    • It utilizes 20% of the body's energy resources.

    Role of Kidney

    • The kidney maintains stable internal body environments.
    • It filters blood plasma, absorbs nutrients and electrolytes, regulates blood pH, and maintains the body's water content.

    Feeding-Fasting Cycle

    • Mammals consume food intermittently due to a mechanism for storing and mobilizing energy-rich molecules from food.
    • Hormonal regulation and substrate concentrations are key factors in controlling metabolism during the feeding-fasting cycle.
    • Postprandial State: After a meal, nutrient levels are high.
    • Post-absorptive State: After an overnight fast, nutrient levels are low.

    Feeding Phase

    • During the postprandial state, nutrients are absorbed and transported via portal blood to the liver.
    • Glucose movement from the intestine to the liver stimulates insulin release from pancreatic-𝛃-cells.
    • Insulin release triggers glucose uptake, glycogenesis, fat synthesis and storage, and protein synthesis.
    • Lipids are transported into lymph as chylomicrons.
    • Chylomicrons supply fatty acids to muscle and adipose tissue and deliver phospholipids, cholesterol, and remaining triglycerides to the liver.
    • The liver uses cholesterol to make bile acids and fatty acids to synthesize phospholipids.
    • Lipids, phospholipids, cholesterol, and proteins are packaged as VLDL for export to tissues.

    Fasting Phase

    • Decreased blood glucose and insulin levels induce glucagon release from pancreatic-𝛂-cells.
    • Glucagon prevents hypoglycemia by stimulating glycogenolysis and gluconeogenesis in the liver.
    • During prolonged fasting, blood glucose is maintained by fatty acid mobilization.
    • Fatty acids become the alternative energy source for muscle during prolonged fasting, conserving glucose for the brain and red blood cells.

    Atherosclerosis

    • Atherosclerosis is the hardening and narrowing of heart arteries due to plaque buildup.
    • Macrophages have receptors similar to LDL receptors that bind and oxidize LDL.
    • In the presence of high LDL, macrophages accumulate more LDL, converting them into foam cells.
    • Foam cells stick to blood vessel walls and promote plaque formation.
    • As foam cells necrose, cholesterol crystals form in the plaques.
    • Atheromas (plaques) can block blood flow and rupture veins.

    High Cholesterol and Drug Therapy

    • High total cholesterol (VLDL, LDL, and HDL) combined with high LDL is strongly associated with cardiovascular disease.
    • Statins, a class of drugs, lower blood cholesterol by inhibiting HMG-CoA reductase.
    • Most cholesterol synthesis occurs at night, so statins are typically taken in the evening.
    • Statin therapy may interfere with ubiquinone (UQ) synthesis, a critical molecule in the electron transport chain.
    • CoQ supplementation may be necessary during statin therapy.

    Role of Gastrointestinal Tract

    • The gastrointestinal (GI) tract mixes, digests, absorbs, and propels food.
    • The stomach secretes ghrelin, a hormone that stimulates appetite.
    • The small intestine secretes peptide YY (PYY), a hormone that inhibits appetite.
    • Pancreatic-𝛃-cells secrete insulin, which stimulates glucose absorption in muscle.
    • Pancreatic-𝛂-cells secrete glucagon, which stimulates catabolism.

    Role of Liver and Muscle

    • The liver plays a crucial role in nutrient metabolism and regulates blood glucose levels.
    • During prolonged fasting (starvation), metabolic changes ensure adequate glucose availability for glucose-requiring cells (brain and red blood cells).
    • Fatty acids from adipose tissue and ketone bodies from the liver are mobilized.
    • Glycogen is depleted after 7 hours of fasting, so gluconeogenesis becomes crucial.
    • Amino acids from muscle protein are used for gluconeogenesis.
    • After several weeks of fasting, the brain adapts to using ketone bodies as an energy source.

    Feeding Behavior

    • Regulating feeding behavior involves hormonal and neuronal signals, as well as sensory input from the environment.
    • These signals are integrated in the brain to regulate appetite.
    • Arcuate Nucleus (ARC): First-order neural circuits that control appetite are located in the hypothalamus.
    • Agouti-related protein (AgRP) and neuropeptide Y (NPY) containing neurons: Activation stimulates appetite.
    • Pro-opiomelanocortin (POMC) peptide containing neurons: Activation inhibits appetite.

    Ghrelin stimulates food intake

    • Ghrelin, an appetite-inducing stomach hormone, activates AgRP/NPY neurons to increase food intake.
    • AgRP/NPY activation also inhibits POMC.

    Leptin inhibits food intake

    • Leptin, insulin, and PYY inhibit AgRP/NPY neurons to reduce food intake.
    • Leptin also activates POMC neurons, further inhibiting appetite and reducing food intake.

    Diabetes Mellitus

    • Diabetes mellitus is a metabolic disease characterized by two types:
      • Type 1 diabetes: Also known as juvenile diabetes or insulin-dependent diabetes. An autoimmune disease caused by destruction of pancreatic-𝛃-cells. Results in inadequate insulin production.
      • Type 2 diabetes: Also known as insulin-independent diabetes. Caused by insulin insensitivity of target cells.
    • In both types, cells fail to acquire glucose from the blood, leading to high blood glucose (hyperglycemia).
    • Hyperglycemia: High blood glucose.
    • Hypoglycemia: Low blood glucose.

    Type 1 Diabetes

    • Symptoms: Ketoacidosis, thirst, frequent urination (polyuria).
    • Treatment: Insulin injection or infusion.

    Type 2 Diabetes

    • Treatment: Diet and exercise.
    • Prolonged uncontrolled Type 2 diabetes can become insulin-dependent.

    Symptoms of Diabetes

    • Hyperglycemia: High blood glucose level.
    • Glycosuria: Presence of glucose in urine. Leads to osmotic diuresis and polyuria (frequent urination, causing excessive thirst).
    • Dyslipidemia: Abnormal blood lipid and lipoprotein levels.

    Obesity

    • Why are many humans predisposed to obesity in the modern world?

    Ketone Body Formation

    • Ketone bodies are formed through a multi-step process.
    • Step 1: Two acetyl-CoA molecules condense to form acetoacetyl-CoA.
    • Step 2: Acetoacetyl-CoA condenses with another acetyl-CoA to form HMG-CoA.
    • Step 3: HMG-CoA lyase hydrolyzes HMG-CoA into acetoacetate.
    • Step 4: Acetoacetate spontaneously decarboxylated to form acetone.
    • Acetoacetate can also be reversibly reduced to beta-hydroxybutyrate.
    • Heart, skeletal muscles and the brain use ketone bodies for energy, especially the brain during prolonged starvation.

    Conversion of Ketone bodies to Acetyl-CoA

    • Ketone bodies can be converted back into acetyl-CoA.
    • Beta-hydroxybutyrate to acetyl-CoA formation occurs in the mitochondrial matrix of the liver.

    Fatty Acid Biosynthesis

    • Fatty acid synthesis takes place in the cytoplasm.
    • Intermediates are covalently linked to acyl carrier protein (ACP), a fatty acid activator in biosynthesis (compare to CoA, which acts as an activator for beta-oxidation).
      • Acetyl-CoA + CO2 → Malonyl-CoA
    • Acetyl-CoA and malonyl-CoA are activated as Acetyl-ACP and Malonyl-ACP for fatty acid synthesis.
    • Four-Step Repeating Cycle (Extension by 2 carbons/cycle):
      • Condensation:
      • Reduction:
      • Dehydration:
      • Reduction:

    Fatty Acid Synthase (FAS)

    • Fatty acid synthase is a multi-enzyme complex that packages the enzymes involved in fatty acid synthesis.
    • Mammals can only synthesize palmitic acid (16:0).
    • Longer and shorter fatty acids, as well as unsaturated fatty acids, are synthesized from palmitic acid.
    • Two carbons are added at a time during fatty acid synthesis.
    • Fatty acid synthesis begins at the methyl end and proceeds towards the carboxyl end.
    • FAS is a X-shaped homodimer of two polypeptides.
      • Each polypeptide contains 7 catalytic domains and ACP.
      • Synthesizes two fatty acids simultaneously.

    Fatty Acid Biosynthesis Phases

    • Phase 1: Synthesis of Malonyl-CoA:
      • Acetyl-CoA carboxylase (ACC1): Carboxylates acetyl-CoA to synthesize malonyl-CoA (irreversible reaction; rate-limiting step in fatty acid biosynthesis).
      • Malonyl-CoA is activated by Malonyl-Acetyl transferase to Malonyl-ACP.
    • Phase 2: Sequential Addition of 2 Carbon Units to Synthesize Palmitic Acid (16:0):
      • Substrates for fatty acid biosynthesis are Acetyl-ACP and Malonyl-ACP:
        • Acetyl-CoA reacts with ACP-SH to form Acetyl-ACP.
        • Malonyl-CoA reacts with ACP-SH to form Malonyl-ACP.
    • Acetyl-ACP Formation:
      • Acetyl-CoA reacts with ACP-SH to form Acetyl-ACP (activated acetate).
      • Acetyl-ACP is transferred to the ketosynthase (KS) unit of the fatty acid synthase complex.

    Fatty Acid Biosynthesis (Phase 2)

    • 1. Condensation:* Acetyl group is transferred to the malonyl group to form acetoacetyl-ACP (catalyzed by KS).
    • 2. Reduction:* Reduction of the beta-carbonyl group forms an alcohol (catalyzed by beta-ketoacyl-ACP reductase (KR).
    • 3. Dehydration:* Removal of water to form a carbon-carbon double bond is catalyzed by beta-hydroxyacyl-ACP dehydratase.
    • 4. Reduction:* Reduction by enoyl-ACP reductase (ER) yields a saturated 4-carbon acyl group.
    • 5. Transfer:* The acyl group is transferred from ACP to the SH group of beta-ketoacyl synthase (KS), starting a new elongation.
    • 6. Elongation:* The acyl chain lengthens by 2 carbons as it condenses with another ACP-linked malonyl group.
    • 7. Termination:* Fatty acid synthesis ends with the release of palmitate from ACP by thioesterase (TE).

    Repeated Cycles for Elongation

    • First Cycle Result: A 4-carbon chain associated with the ACP arm is transferred back to the KS arm. A new malonyl-CoA is introduced on the ACP arm.
    • Subsequent Cycles: The reactions proceed as before. For each cycle, the acyl group is transferred to the alpha-carbon of malonyl-CoA, making it 2 carbons longer than the previous cycle.
    • Final Product: After 7 cycles, a 16-carbon fatty acid (palmitoyl-ACP) is attached to the ACP arm, hydrolyzed from ACP to yield free palmitate.
    • Net Reaction:* 8 acetyl-CoA + 14 NADPH + 17 H+ + 7 ATP → Palmitate + 14 NADP+ + 7 ADP + 7 Pi + 8 CoASH + 6 H2O.

    Acetyl-CoA Carboxylase (ACC)

    • Key Enzyme in Fatty Acid Synthesis: Acetyl-CoA carboxylase (ACC1) catalyzes the rate-limiting step in fatty acid synthesis.
    • Active and Inactive Forms:
      • Active Form: Polymerized-Dephosphorylated (Dimer).
      • Inactive Form: Phosphorylated Monomer.

    Allosteric Regulation of ACC1

    • Activator:
      • Citrate: A feedforward activator that promotes polymerization of ACC1.
    • Inhibitor:
      • Palmitoyl-CoA: The end product of fatty acid synthesis depolymerizes to inhibit ACC1.

    Hormonal Regulation of ACC1

    • Insulin: Dephosphorylates and activates ACC1.
    • Epinephrine and Glucagon: Phosphorylates and inhibits ACC1.

    Fatty Acid Elongation and Desaturation

    • Closely Integrated Processes: Fatty acid elongation and desaturation occur in the endoplasmic reticulum (ER), which is essential for regulating membrane fluidity.
    • Initial Activation: Palmitoyl-CoA is activated to palmitoyl-CoA for both elongation and desaturation.
    • Elongation: Two-carbon units are supplied by malonyl-CoA. Elongases synthesize longer-chain fatty acids.
    • Desaturation: Desaturases synthesize unsaturated fatty acids, specific for specific positions of the double bond.
    • Mammals Lack Enzyme for C9 and Beyond: Mammals cannot introduce double bonds beyond carbon 9. Fatty acids with double bonds beyond carbon 9 are obtained by diet.

    Desaturases and Double Bond Positions

    • Desaturases are specific to the positions of the double bond.

    Similarities Between Fatty Acid Synthesis and Beta-Oxidation

    • Fatty acid synthesis appears as the reverse of beta-oxidation.
    • Fatty acids are synthesized by sequential addition of 2-carbon groups supplied by malonyl-CoA.
    • Beta-oxidation removes 2-carbon groups as acetyl-CoA.
    • Both pathways share the same intermediates: beta-ketoacyl (1), beta-hydroxyacyl (2), alpha,beta-unsaturated acyl (3).

    Differences Between Fatty Acid Synthesis and Beta-Oxidation

    • Location: Fatty acid synthesis occurs in the cytoplasm; beta-oxidation occurs in mitochondria and peroxisomes.
    • Redox Cofactors: Fatty acid synthesis consumes NADPH; beta-oxidation generates NADH and FADH2.
    • Enzymes: Different enzymes are used in fatty acid synthesis and beta-oxidation.
    • Intermediates: Fatty acid synthesis intermediates are linked to acyl carrier protein (ACP).

    Fatty Acid Synthesis

    • Fatty acid synthesis occurs via a series of cycles, each adding a 2-carbon unit to the growing fatty acid chain, derived from malonyl-CoA.
    • The process requires 7 cycles to synthesize palmitate (16 carbons).
    • The enzyme Acetyl-CoA carboxylase (ACC1) catalyzes the committed step of fatty acid biosynthesis, converting acetyl-CoA to malonyl-CoA.
    • ACC1 exists in active (polymerized and dephosphorylated) and inactive (monomer, phosphorylated) forms.
    • Citrate, a feedforward activator, promotes the polymerization of ACC1.
    • Palmitoyl-CoA, the end product of fatty acid synthesis, inhibits ACC1 by promoting depolymerization.
    • Insulin activates ACC1 by dephosphorylating it, while epinephrine and glucagon inhibit ACC1 by phosphorylating it.

    Fatty Acid Elongation and Desaturation

    • Fatty acid elongation and desaturation occur in the endoplasmic reticulum (ER), playing a crucial role in regulating membrane fluidity.
    • Elongation enzymes (elongases) synthesize longer fatty acid chains by adding 2-carbon units from malonyl-CoA to palmitoyl-CoA.
    • Desaturases introduce double bonds into fatty acid chains at specific positions.
    • Mammals lack the enzymes to introduce double bonds beyond carbon 9. Therefore, essential fatty acids containing double bonds beyond carbon 9 must be acquired through diet.

    Similarities and Differences between Fatty Acid Synthesis and Beta-Oxidation

    • Although seemingly reversed, fatty acid synthesis and beta-oxidation share common intermediates: beta-ketoacyl (1), beta-hydroxyacyl (2), and alpha,beta-unsaturated acyl (3).
    • Both pathways utilize similar enzymes, but key differences exist:
      • Location: Fatty acid synthesis occurs in the cytoplasm, while beta-oxidation occurs in mitochondria and peroxisomes.
      • Redox: Fatty acid synthesis consumes NADPH, while beta-oxidation generates NADH and FADH2.
      • Carrier: Fatty acid synthesis intermediates are linked to acyl carrier protein (ACP), while beta-oxidation intermediates are attached to CoA.

    Phospholipids

    • Two main phospholipid classes: phosphoglycerides and sphingomyelins.
    • Phosphatidylethanolamine (cephalin): Stabilizes membrane curvature, composing 25% of human phospholipids.
    • Phosphatidylcholine (PC): Acts as a surfactant and is a major component of biological membranes.
    • Phosphatidylserine (PS): Signals macrophages to engulf cells, playing a crucial role in biological membranes.
    • Synthesis:
      • Ethanolamine and choline enter the cell and are phosphorylated.
      • Phospho-ethanolamine and phospho-choline react with CTP to form CDP-ethanolamine and CDP-choline, respectively.
      • Diacylglycerol is synthesized from triacylglycerol.
      • CDP-ethanolamine and CDP-choline react with diacylglycerol to form phosphatidylethanolamine and phosphatidylcholine.
    • Turnover: Phospholipid turnover is rapid, involving the replacement of fatty acids.
      • Phospholipases (PLA) degrade phospholipids:
        • PLA1: Hydrolyzes the ester bond at C1 of glycerol.
        • PLA2: Hydrolyzes the ester bond at C2 of glycerol.
        • PLB: Hydrolyzes both C1 and C2 ester bonds.
        • PLC: Hydrolyzes the phosphodiester bond between glycerol and phosphate.
        • PLD: Hydrolyzes the phosphodiester bond between phosphate and fatty acid (R3).

    Sphingosine, Ceramide, Sphingomyelin and Glycosphingolipids

    • Sphingosine synthesis: Palmitoyl-CoA condenses with serine to form sphinganine (palmitoyl-CoA + serine -> sphinganine).
    • Ceramide synthesis: Sphinganine reacts with a long-chain fatty acid to form ceramide (sphinganine + long-chain fatty acid -> ceramide).
    • Sphingomyelin synthesis: Ceramide reacts with phosphatidylcholine or phosphatidylethanolamine to form sphingomyelin (ceramide + phosphatidylcholine or phosphatidylethanolamine -> sphingomyelin).
    • Galactocerebroside synthesis: Ceramide reacts with UDP-galactose to form galactocerebroside (ceramide + UDP-galactose -> galactocerebroside).
    • Glucocerebroside synthesis: Ceramide reacts with UDP-glucose to form glucocerebroside (ceramide + UDP-glucose -> glucocerebroside).

    Sphingomyelin Metabolism and Cerebrosides Metabolism

    • Sphingomyelin: The hydroxyl group of ceramide is esterified to the phosphate group of either phosphorylcholine or phosphorylethanolamine.
      • Involved in nerve insulation and rapid nerve impulse transmission.
      • Degraded by sphingomyelinase.
      • Accumulation of sphingomyelin due to defective sphingomyelinase leads to Niemann-Pick Syndrome.
    • Cerebrosides: Monosaccharides are the head groups in cerebrosides, they are important components of myelin sheaths, the insulating covering around nerve fibers.

    Cholesterol Metabolism

    • Cholesterol synthesis: The rate-limiting enzyme in cholesterol synthesis is HMG-CoA reductase.
    • HMG-CoA reductase is regulated by:
      • Steroid hormones: Promote cholesterol.
      • Insulin: Stimulates cholesterol synthesis.
      • Glucagon: Inhibits cholesterol synthesis.
    • LDL: Low-density lipoprotein transports cholesterol from the liver to the tissues
    • HDL: High-density lipoprotein transports cholesterol from tissues back to the liver.
    • Atherosclerosis: Hardening and narrowing of arteries due to plaque buildup.
      • Oxidized LDL binds to macrophage receptors similar to LDL receptors.
      • Macrophages accumulate LDL, transforming into foam cells.
      • Foam cells contribute to plaque formation, leading to narrowed arteries and potentially blocking blood flow.

    High Cholesterol and Drug Therapy

    • High total cholesterol, especially high LDL, is strongly linked to cardiovascular disease.
    • Statins (e.g., Lipitor, Atorvastatin, Crestor), a class of drugs, lower blood cholesterol by inhibiting HMG-CoA reductase.
    • Statins are often taken in the evening as most cholesterol synthesis occurs at night.
    • Statins may interfere with ubiquinone (UQ) synthesis, which is crucial for the electron transport chain. Supplementation with CoQ may be necessary.

    Integration of Metabolism (Feeding-Fasting Cycle)

    • Organs involved in metabolic workload: gastrointestinal tract (including pancreas), liver, muscle (skeletal and cardiac), adipose tissue, brain, and kidneys.
    • Gastrointestinal tract: Mixes, digests, absorbs, and propels food.
      • Stomach: Secretes ghrelin, a hormone that stimulates appetite.
      • Small intestine: Secretes peptide YY (PYY), a hormone that inhibits appetite.
      • Pancreatic-β-cells: Secrete insulin, a hormone that stimulates glucose absorption in muscle.
      • Pancreatic-α-cells: Secrete glucagon, a hormone that stimulates catabolism.
    • Liver: Plays a key role in nutrient metabolism and regulating blood glucose levels.
      • During prolonged fasting, the liver synthesizes ketone bodies from fatty acids, providing an alternative energy source for the brain.
    • Muscle: Uses glucose for energy and stores carbohydrates as glycogen.
      • During prolonged fasting, muscle protein is broken down to provide amino acids for gluconeogenesis in the liver.

    Feeding Behavior

    • Regulating feeding behavior involves hormonal and neuronal signals, as well as sensory input.
    • The hypothalamus, specifically the arcuate nucleus (ARC), plays a central role in appetite regulation.
    • The ARC consists of two types of neurons:
      • Agouti-related protein (AgRP) and neuropeptide Y (NPY) neurons: Stimulates appetite.
      • Pro-opiomelanocortin (POMC) neurons: Inhibits appetite.
    • Ghrelin: A stomach hormone that stimulates food intake by activating AgRP/NPY neurons and inhibiting POMC neurons.
    • Leptin, insulin, and PYY: Hormones that inhibit food intake by inhibiting AgRP/NPY neurons and activating POMC neurons.

    Diabetes Mellitus

    • A metabolic disease characterized by high blood glucose levels and cellular inability to acquire glucose from the blood.
    • Two main types:
      • Type 1 Diabetes (insulin-dependent): Autoimmune disease caused by destruction of pancreatic-beta cells, leading to inadequate insulin production.
      • Type 2 Diabetes (insulin-independent): Characterized by insulin resistance in target cells.
    • Symptoms:
      • Hyperglycemia (high blood glucose): Common to both type 1 and type 2 diabetes.
      • Glycosuria (glucose in urine): Leads to osmotic diuresis and polyuria (frequent urination) causing excessive thirst.
      • Dyslipidemia (abnormal blood lipid): Abnormal blood lipid and lipoprotein levels.

    Obesity

    • Obesity is a complex condition influenced by genetic predisposition, environmental factors, and lifestyle choices.
      • It is strongly associated with increased risk of cardiovascular disease, type 2 diabetes, cancer, and other health issues.
      • Treatment often involves lifestyle changes such as diet modification, exercise, and behavioral therapy.

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    Description

    Test your knowledge on the roles of skeletal muscle, adipose tissue, brain, and kidney in metabolism. Explore how these organs interact during the feeding-fasting cycle and their significance in energy balance. This quiz is perfect for students studying human biology or physiology.

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