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Questions and Answers

In inherited sucrase deficiency, what is the primary consequence of the absence of the sucrase enzyme?

  • Increased absorption of fructose in the small intestine.
  • Enhanced production of glucose from galactose.
  • Inability to digest sucrose, leading to distension and colic. (correct)
  • Stimulation of glycogen synthesis in the liver.

Which of the following monosaccharides is primarily absorbed via simple diffusion?

  • Galactose
  • Fructose (correct)
  • Glucose
  • Sucrose

How does Ouabain affect glucose absorption in the intestines?

  • It directly inhibits the SGLT-1 transporter.
  • It promotes facilitated diffusion of glucose.
  • It inhibits the $Na^+-K^+$ pump, reducing the sodium gradient needed for glucose cotransport. (correct)
  • It enhances the activity of GLUT-5 transporters.

If blood glucose levels exceed the renal threshold (180 mg/dL), what is the likely consequence?

<p>Glucose excretion in the urine. (C)</p> Signup and view all the answers

What is the primary purpose of the hexose monophosphate pathway and uronic acid pathway in glucose oxidation?

<p>Formation of important metabolites. (A)</p> Signup and view all the answers

During glycolysis, which enzyme facilitates the conversion of glucose to glucose-6-phosphate?

<p>Hexokinase or glucokinase (D)</p> Signup and view all the answers

What is the role of phosphofructokinase-1 (PFK-1) in glycolysis?

<p>To phosphorylate fructose-6-phosphate to fructose-1,6-bisphosphate. (C)</p> Signup and view all the answers

Which enzyme converts dihydroxyacetone phosphate to glyceraldehyde-3-phosphate during glycolysis?

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

During intense muscle contraction, elevated calcium levels stimulate which enzymes in the citric acid cycle to enhance energy supply?

<p>Citrate synthase, isocitrate dehydrogenase, and $\alpha$-ketoglutarate dehydrogenase (D)</p> Signup and view all the answers

Under anaerobic conditions, the citric acid cycle is inhibited due to which of the following reasons?

<p>Inhibition of the respiratory chain leading to an elevated NADH/NAD+ ratio (B)</p> Signup and view all the answers

Which of the following conditions would inhibit the activity of citrate synthase, isocitrate dehydrogenase, and $\alpha$-ketoglutarate dehydrogenase?

<p>High ATP/ADP ratio (D)</p> Signup and view all the answers

Which eicosanoid primarily contributes to reducing cAMP levels in platelets, promoting thrombus formation, and causing vasoconstriction?

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

Which of the listed disaccharides is commonly found in table sugar?

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

How do steroidal anti-inflammatory drugs alleviate bronchial asthma and anaphylactic shock?

<p>By inhibiting phospholipase A2, reducing arachidonic acid release and subsequent eicosanoid synthesis. (A)</p> Signup and view all the answers

Why are blood samples for glucose estimation often collected in test tubes containing glycolysis inhibitors?

<p>To ensure accurate measurement of glucose by preventing its consumption by cells. (A)</p> Signup and view all the answers

In the digestive system, which enzyme initiates the breakdown of starch in the mouth?

<p>Salivary Amylase (C)</p> Signup and view all the answers

Certain prostaglandins increase cAMP levels in endocrine glands. What is the subsequent effect of this action?

<p>Increased hormonal secretion (D)</p> Signup and view all the answers

Phosphofructokinase-2 (PFK-2) is described as a bifunctional enzyme. Which of the following best describes its dual activity?

<p>It functions as both a kinase and a phosphatase, with their activity being inversely regulated. (C)</p> Signup and view all the answers

A patient experiencing severe allergic reaction (anaphylactic shock) would likely exhibit symptoms associated with which type of eicosanoid?

<p>Leukotrienes due to their role in bronchospasm and blood pressure drop. (B)</p> Signup and view all the answers

What is the primary reason for distension and colic in infants with inherited lactase deficiency?

<p>Fermentation of undigested lactose by intestinal bacteria (D)</p> Signup and view all the answers

If a patient's cells are unable to convert pyruvate into oxaloacetate, which of the following substances would be essential to supplement?

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

How does increased succinyl-CoA affect the citric acid cycle?

<p>It inhibits citrate synthase and $\alpha$-ketoglutarate dehydrogenase (A)</p> Signup and view all the answers

Which of the following best describes the mechanism by which aspirin prevents thrombus formation?

<p>Inhibiting cyclooxygenase, which reduces thromboxane formation in platelets. (B)</p> Signup and view all the answers

Through which process does $\alpha$-ketoglutarate transform into glutamate?

<p>Transamination (C)</p> Signup and view all the answers

In a cell with high levels of Acetyl-CoA, what effect is expected on the activity of pyruvate carboxylase and why?

<p>Activation, because Acetyl-CoA acts as an allosteric activator, promoting oxaloacetate production. (B)</p> Signup and view all the answers

If a drug inhibits the synthesis of prostaglandins and thromboxanes, which enzyme is most likely being targeted?

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

Which of the following phospholipids is also known as lipositol?

<p>Phosphatidyl-inositol (B)</p> Signup and view all the answers

Which of the following conditions would inhibit the pyruvate dehydrogenase (PDH) complex?

<p>Increased ratio of ATP to ADP. (C)</p> Signup and view all the answers

During intense exercise, muscle cells produce lactate. How is this lactate primarily utilized when the body returns to a resting state?

<p>Converted back to pyruvate by lactate dehydrogenase. (A)</p> Signup and view all the answers

What is the direct precursor molecule in the synthesis of phosphatidyl ethanolamine and phosphatidyl choline?

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

How many ATP molecules are generated from the oxidative decarboxylation of two pyruvate molecules into two Acetyl-CoA molecules?

<p>5 ATP (A)</p> Signup and view all the answers

Which of the following tissues is LEAST likely to have active pentose phosphate pathway (HMP)?

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

In sphingolipid catabolism, a deficiency in lysosomal hydrolase enzymes would directly result in:

<p>Accumulation of complex lipids in tissues. (A)</p> Signup and view all the answers

Which of the following conditions results from a deficiency in the enzyme sphingomyelinase?

<p>Niemann-Pick Disease, with accumulation of sphingomyelin. (B)</p> Signup and view all the answers

What is the primary endogenous source of cholesterol synthesis?

<p>Active acetate (acetyl-CoA). (D)</p> Signup and view all the answers

How does carbohydrate feeding impact HMG-CoA reductase activity?

<p>It decreases cAMP levels, activating HMG-CoA reductase. (D)</p> Signup and view all the answers

Which of the following is NOT a direct role of cholesterol in the body?

<p>Precursor for the synthesis of nucleic acids. (B)</p> Signup and view all the answers

What stimulates the key enzyme (7 α - hydroxylase) in bile acid synthesis?

<p>Thyroid hormones and vitamin C. (C)</p> Signup and view all the answers

If a patient has a deficiency in the enzyme $\beta$-Glucosidase, which complex lipid would accumulate in their tissues?

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

Which regulatory mechanism directly involves covalent modification of HMG-CoA reductase?

<p>Regulation through phosphorylation and dephosphorylation. (C)</p> Signup and view all the answers

Which of the following best describes the primary consequence of defective chylomicron, VLDL, and LDL formation?

<p>Impaired lipid transport, potentially leading to fatty liver and other complications. (D)</p> Signup and view all the answers

Hypoalphalipoproteinemia, resulting from a failure in apo-A synthesis, primarily affects the formation of which lipoprotein?

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

A deficiency in LCAT (lecithin-cholesterol acyltransferase) would directly lead to what outcome?

<p>Marked decrease in cholesterol esters and elevated disk-shaped HDL. (B)</p> Signup and view all the answers

Excessive accumulation of triacylglycerols (TAG) in the liver, leading to fatty liver, can cause what sequence of pathological events?

<p>Liver enlargement, pressure atrophy of liver cells, hepatic dysfunction, and potentially liver cirrhosis. (D)</p> Signup and view all the answers

Which scenario would most likely lead to over-mobilization of fat from adipose tissue to the liver:

<p>Untreated diabetes mellitus (B)</p> Signup and view all the answers

A deficiency in pantothenic acid can lead to fatty liver by directly impairing:

<p>The synthesis of Coenzyme A (CoA). (C)</p> Signup and view all the answers

Lipotropic factors facilitate the mobilization of fat from the liver. What is the most direct mechanism by which these factors accomplish this?

<p>Promoting lipoprotein synthesis. (D)</p> Signup and view all the answers

Excessive intake of nicotinic acid can lead to depletion of methyl donors, potentially affecting phospholipid synthesis. How does this occur?

<p>Nicotinic acid is excreted in urine as n-methylnicotinamide, consuming methyl groups. (C)</p> Signup and view all the answers

Flashcards

Glutamate Source

Formed from α-ketoglutarate via transamination.

Aspartate Source

This is formed from oxaloacetate.

Acetyl-CoA and Oxaloacetate

It activates citrate synthase in the citric acid cycle.

Succinyl-CoA

It inhibits citrate synthase and α-ketoglutarate dehydrogenase.

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High Energy Signals

High NADH/NAD+ and ATP/ADP ratios inhibit citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase.

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Calcium's Role in Krebs

Elevated calcium activates citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase.

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Common Monosaccharides

Glucose, fructose, and galactose.

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Common Disaccharides

Sucrose, lactose, and maltose.

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Inherited Sucrase Deficiency

A condition where the sucrase enzyme is deficient, leading to undigested sucrose, causing distension and colic. Typically occurs later in life.

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Simple Diffusion (Monosaccharides)

Fructose and pentoses are absorbed through the intestinal membrane down their concetration gradient without the need of a transport protein.

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Facilitated Transport

Fructose, glucose and galactose are absorbed with the help of a protein transporter (GLUT-5).

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Active Transport (Monosaccharides)

Glucose and galactose are absorbed needing energy (ATP).

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Inhibitors of Glucose Absorption

Ouabain inhibits the Na+/K+ pump and Phlorhizin inhibits glucose absorption in the intestine and renal tubules.

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Fates of Absorbed Glucose

Glucose can be oxidized for energy, converted to other sugars, used to build glycerol-3-P and non-essential amino acids, stored as glycogen/triacylglycerol, or excreted in urine if the renal threshold is exceeded.

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Glycolysis

The oxidation of glucose into pyruvate (aerobic) or lactate (anaerobic).

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Glycolysis Step 1

Hexokinase converts glucose to glucose-6-phosphate, trapping glucose inside the cell.

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Prostaglandins

Contraction of smooth muscles, stimulation of uterine contraction, increased cAMP in some endocrine glands, decreased cAMP in the stomach.

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Prostacyclins (PGI2)

Vasodilation and inhibition of platelet aggregation via increased cAMP in platelets.

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Thromboxanes

Vasoconstriction and promotion of platelet aggregation by decreasing cAMP in platelets.

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Leukotrienes

Bronchospasm, vasodilation, drop in blood pressure; involved in allergic reactions.

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NSAIDs (e.g., Aspirin)

Inhibit cyclooxygenase, reducing inflammation and thromboxane formation.

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Steroidal Anti-inflammatory Drugs (e.g., Cortisone)

Inhibit phospholipase A2, preventing arachidonic acid release and eicosanoid synthesis.

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Phosphoglycerides

Phospholipids with a glycerol backbone.

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Sphingolipids

Phospholipids with a sphingosine backbone.

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Glycolysis Inhibitor

Substance added to blood samples for glucose estimation to stop glycolysis.

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Phosphofructokinase-2

A bifunctional enzyme with both kinase (adds phosphate) and phosphatase (removes phosphate) activity, regulated inversely.

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Sources of Pyruvate

Pyruvate can be derived from glucose, glycerol-3-P and lactate.

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Fate of Pyruvate

Pyruvate can be converted into oxaloacetate, acetyl-CoA, lactate and alanine.

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Pyruvate Carboxylase

Converts pyruvate to oxaloacetate. Activated by glucagon/adrenaline and Acetyl CoA. Inhibited by insulin.

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Pyruvate Dehydrogenase (PDH) Complex

Converts Pyruvate to Acetyl CoA. Requires 3 enzymes and 5 coenzymes.

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Regulation of Pyruvate Dehydrogenase

Activated by: Insulin, pyruvate, CoASH, NAD, ADP & Ca2+. Inhibited by: Acetyl CoA, NADH, ATP

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Hexose Monophosphate Pathway (HMP)

A minor pathway for glucose oxidation producing pentose-5-P and NADPH. Occurs in the cytoplasm of liver, mammary glands, RBCs and adrenal glands.

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Sphingolipid Catabolism

Catalysis of sphingolipids is performed by a group of lysosomal hydrolase enzymes.

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Hypobetalipoproteinemia

Defective formation of chylomicrons, VLDL, and LDL due to genetic defects.

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Sphingolipidosis

Lipid storage diseases caused by a deficiency in sphingolipid catabolic enzymes, leading to complex lipid accumulation in tissues.

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Hypoalphalipoproteinemia

Failure to synthesize apo-A, resulting in decreased HDL formation.

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Gaucher's Disease

A disease caused by a deficiency in β-Glucosidase, leading to the accumulation of glucocerebrosides.

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LCAT Deficiency

A deficiency leading to decreased cholesterol esters and elevated disk-shaped HDL.

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Fatty Liver

Excessive accumulation of TAG in the liver, exceeding 40% of its weight.

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Niemann-Pick Disease

A disease caused by a deficiency in sphingomyelinase, leading to accumulation of sphingomyelin.

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Cholesterol Synthesis Site

Every cell and the liver (plasma cholesterol) through active acetate (acetyl-CoA).

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Carb Overfeeding (Fatty Liver)

Excessive carbs stored as glycogen, then converted to TAGs via lipogenesis.

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Regulation of Cholesterol Synthesis

Carbohydrate/insulin: decreases cAMP, increases HMG-CoA reductase activity. Fasting/glucagon: decreases its activity. Feedback inhibition: mevalonate and cholesterol inhibit HMG-CoA reductase.

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Pantothenic Acid Deficiency

Insufficient pantothenic acid (for CoA) impairs fatty acid oxidation.

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Lipotropic Factors

Factors needed for lipoprotein synthesis, aiding fat mobilization from the liver.

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Importance of Cholesterol

Component of cell membranes, forms plasma lipoproteins, precursor to Vitamin D3, steroid hormones, and bile acids/salts.

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Liver Toxins

Toxins that decrease protein synthesis, affecting lipoprotein production.

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Bile Acid Synthesis

Key enzyme: 7 α - hydroxylase. Stimulated by thyroid hormones and vitamin C, inhibited by bile salts. Forms primary bile acids (cholic and chenodeoxycholic acids).

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Study Notes

Bioenergetics and Metabolism

  • Metabolism is a reaction series of biochemical processes involving biomolecules in living organisms, including anabolic and catabolic reactions.

Anabolism

  • Anabolism is the synthesis of macromolecules from simpler molecules, a process that is usually endergonic, requiring energy input.
  • Examples include the synthesis of polysaccharides from monosaccharides, triacylglycerol from glycerol and fatty acids, and proteins from amino acids.

Catabolism

  • Catabolism is the breakdown of macromolecules into simpler components which is exergonic releasing energy.
  • Catabolism occurs in three stages:
    • Stage I involves the digestion of proteins, lipids, and carbohydrates.
    • Stage II involves the formation of amino acids, glycerol, fatty acids, and monosaccharides.
    • Stage III involves the formation of Acetyl CoA.

Bioenergetics

  • Energy is stored in two types of bonds: low energy and high energy, with the key difference is the amount of energy released upon hydrolysis, in Kcal/mole.
  • Low energy bonds release less than 7.3 Kcal/mole upon hydrolysis, and they link food stuffs, such as Glycosidic bonds in carbohydrates, Carboxyl-ester bonds in triacylglycerol, and Peptide bonds in protein.
  • High energy bonds release more than 7.3 Kcal/mole upon hydrolysis.

ATP

  • Released energy is collected in the form of ATP in two forms:
    • Substrate level oxidative phosphorylation reactions
    • Electron transport chain (respiratory chain) level.

Substrate Level Phosphorylation

  • Reactions produce energy directly in the form of ATP.
  • ATP is produced at the substrate level in two reactions in glycolysis and one in the citric acid cycle.
  • Krebs' cycle: One reaction is Succinyl Co A with thiokinase, resulting in succinate + ATP
  • Glycolysis: 2 reactions involve Biphospoglycerate (phosphoglycerate kinase to phosphoglycerate +ATP) and Phosphoenol pyruvate (pyruvate kinase to pyruvate + AТР)

Electron Transport Chain

  • Electron transport chains or respiratory chains consist of a series of hydrogen transfers from complexes that are more electronegative to oxygen an electropositive form of water,which releases energy in the form of ATP.

Electron Transport Chain Components

  • Components are present in 4 complexes, CoQ, and cytochrome c
  • Complex I consists of FMN, NADH dehydrogenase (7FeS groups) and many polypeptides and transfers it to CoQ forming (CoQH2) with production of one ATP.
  • Complex II consists of FAD Succinate dehydrogenase, and 2 FeS groups where FADH2 transfers hydrogen from succinate to CoQ to form CoQH2 without production of ATР.
  • CoQ is the main station between complex I and complex II.
  • Complex III consists of Cytochromes b & C and one iron sulfur FeS group that transfers electrons from CoQH: to cytochrome releasing four protons with production of one ATP.
  • Complex IV consists of Cytochromes a-a3 (a hemoprotein contains iron) and 2 Copper atoms that transfers electrons from cytochrome c to oxygen which combines with the two protons to form water with of production 0.5ATP.
    • Flavoproteins exist in Complex I as FMN and Complex II as FAD.
    • Protons are pumped through complexes I, III & IV.

Chemiosmotic Theory of ATP Synthesis

  • Chemiosmotic theory of ATP synthesis involves ATP synthase enzyme (complex V), consisting of two subunits, F0 and F1.
    • The F0 subunit through which protons return to the mitochondrial matrix according to their concentration gradients.
    • Coupled with the F1 subunit couples ADP with Pi to form ATP.

ATP Transporter

  • ATP Transporter (Translocater) exchanges ADP to (ATP formed in respiratory chain) to avoid inhibition of ETC by the accumulated ATP.

Regulation of respiratory chain

  • Respiratory chain is inhibited in the absence of oxygen (under anaerobic conditions).
  • ADP and AMP are the major control substances of E.T.C. -E.T.C. is inhibited by excess ATP (energy in the cell) and is stimulated by ADP and highly stimulated by AMP.

P/O Ratio

  • P/O ratio is the ratio between inorganic phosphate consumed to form ATP in relation to the oxygen atom reduced to form water in the respiratory chain.
    • Oxidation of NADH,H = 2.5 ATPs, formed at 3 coupling sites.
    • Oxidation of FADH2 = 1.5 ATPs, formed at 2 coupling sites.

Storage of energy

  • Energy is stored in the form of creatine phosphate in muscles, collected in the form of ATP and starts this reaction: Creatine + ATP via Creatine phosphokinase (CPK), creates Creatine ~P ++ ADP.

Uncouplers

  • Uncouplers dissociate oxidation from phosphorylation and include physiological uncouplers:
    • Calcium ions, Thyroxin hormone and Thermogenin (physiological uncoupler present in adipose tissue), responsible for energy released as heat and in human babies who cannot shiver to generate heat
  • Pharmacological uncouplers : 2,3 Dinitrophenol affect ion and proton transport through the mitochondrial membrane and disrupt electrochemical gradients, allowing protons to pass through gate F2 and release energy as heat.

The Citric Acid Cycle

  • The citric acid cycle (also known as the Krebs Cycle) is a series of chemical reactions for the complete oxidation of active acetate (acetyl ~ SCoA) derived from carbohydrates, fats, and proteins.
  • All components of the cycle are located freely in the mitochondrial matrix except succinate dehydrogenase, which is present in the inner mitochondrial membrane.

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