Biology Chapter: Plasma Membrane Structure
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Questions and Answers

What role does cholesterol play in the cellular membrane?

  • It stiffens the membrane by connecting phospholipids. (correct)
  • It acts as a signal molecule.
  • It forms the hydrophobic barrier of the bilayer.
  • It allows for cell communication.

What characteristic of phospholipids contributes to the formation of the lipid bilayer?

  • They are amphipathic with hydrophilic heads and hydrophobic tails. (correct)
  • They form single-layer membranes only.
  • They are all nonpolar molecules.
  • They spontaneously repel water.

Why is the hydrophobic core of the lipid bilayer important?

  • It allows the passage of water-soluble substances.
  • It prevents the diffusion of water-soluble (hydrophilic) solutes. (correct)
  • It facilitates the movement of lipids.
  • It enables cell division.

Which component of the plasma membrane is involved in cell-to-cell recognition?

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

Which of the following is NOT a property of the lipid bilayer?

<p>It has a hydrophilic core. (C)</p> Signup and view all the answers

What is the function of glycolipids in the plasma membrane?

<p>To act as signal molecules. (D)</p> Signup and view all the answers

Which lipid class is characterized by having a glycerol backbone?

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

What contributes to the stability of the lipid bilayer structure?

<p>Hydrophobic interactions and van der Waals forces. (B)</p> Signup and view all the answers

What role do peripheral membrane proteins primarily play in relation to the membrane?

<p>They interact with integral membrane proteins or lipid head groups. (C)</p> Signup and view all the answers

Which characteristic defines transmembrane proteins?

<p>They can possess one or more membrane-spanning regions. (C)</p> Signup and view all the answers

What type of proteins are anchored to membranes by hydrophobic carbon chains?

<p>Covalently attached lipid proteins. (D)</p> Signup and view all the answers

How do cytoskeletal filaments relate to peripheral proteins?

<p>They interact indirectly through adapter proteins. (C)</p> Signup and view all the answers

Which statement is true regarding the orientation of lipid-anchored proteins?

<p>They have an asymmetrical location relative to membrane faces. (D)</p> Signup and view all the answers

Which function is associated with membrane proteins involved in transport?

<p>They provide a hydrophilic channel for solute transport. (B)</p> Signup and view all the answers

What is a common feature of both single-pass and multipass transmembrane proteins?

<p>They possess at least one membrane-spanning region. (C)</p> Signup and view all the answers

What primarily distinguishes integral membrane proteins from peripheral membrane proteins?

<p>Integral proteins penetrate the hydrophobic core of the bilayer. (D)</p> Signup and view all the answers

What occurs during the transition from E1 to E2 in the Na+/K+ ATPase mechanism?

<p>The affinity for Na+ ions decreases. (B)</p> Signup and view all the answers

How do Na+ ions dissociate from the Na+/K+ ATPase during the E2 conformation?

<p>They dissociate one at a time despite high extracellular Na+ concentration. (B)</p> Signup and view all the answers

What happens to K+ ions during the transition from E2 to E1 in the Na+/K+ ATPase?

<p>They are released into the cytosol. (B)</p> Signup and view all the answers

Which statement is true regarding the effect of certain drugs like ouabain on the Na+/K+ ATPase?

<p>They disrupt the Na+/K+ balance by inhibiting ATPase activity. (A)</p> Signup and view all the answers

What drives the uphill transport of glucose into the cell at the apical end via the glucose-Na+ symport?

<p>The Na+ gradient established by the Na+ pump. (D)</p> Signup and view all the answers

What role do microfilaments play in relation to membrane proteins?

<p>They assist in maintaining cell shape and stabilizing protein locations. (A)</p> Signup and view all the answers

How does a hypotonic solution affect cells?

<p>Cells swell as water flows into them. (B)</p> Signup and view all the answers

What is the primary function of the plasma membrane?

<p>To act as a permeability barrier. (A)</p> Signup and view all the answers

What happens when cells are placed in a hypertonic solution?

<p>The cells will shrink as water exits. (A)</p> Signup and view all the answers

What distinguishes an isotonic solution for animal cells?

<p>Has an equal total concentration of solutes to the cell interior. (B)</p> Signup and view all the answers

What is a key characteristic of the plasma membrane surrounding organelles?

<p>It contains a unique set of essential proteins. (C)</p> Signup and view all the answers

What is the process of osmosis primarily driven by?

<p>Differences in solute concentration. (C)</p> Signup and view all the answers

Which of the following best describes what happens to water during osmosis?

<p>Water moves towards a low water concentration area. (D)</p> Signup and view all the answers

What is the primary energy source used by ATP-powered pumps during active transport?

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

What characterizes the transport process via non-gated ion channels?

<p>They allow the passage of ions down their concentration gradient. (D)</p> Signup and view all the answers

Which of the following best explains the concept of electrochemical gradient?

<p>The combination of concentration gradient and electric potential affecting ion movement. (B)</p> Signup and view all the answers

Which type of transporter does GLUT1 represent?

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

What primarily maintains the inside-negative electric potential of animal cell membranes?

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

What differentiates gated channel proteins from non-gated channel proteins?

<p>Gated proteins open in response to specific signals. (C)</p> Signup and view all the answers

Which mechanism does a uniporter use to transport molecules?

<p>Facilitated diffusion down the gradient (A)</p> Signup and view all the answers

Which statement is true regarding the function of ATPases in active transport?

<p>They move substances against a concentration or electric potential gradient. (C)</p> Signup and view all the answers

What is the primary role of the Na+/Ca2+ antiporter in cardiac muscle cells?

<p>To maintain low intracellular Ca2+ concentration (A)</p> Signup and view all the answers

How do inhibitors of the Na+/K+ ATPase, like Digitalis, affect cardiac muscle contractions?

<p>They increase the intracellular concentration of Ca2+ (A)</p> Signup and view all the answers

What effect does ouabain have on the Na+/K+ ATPase?

<p>It inhibits the pump and locks Na+ in (C)</p> Signup and view all the answers

What is the function of V-class H+ ATPases?

<p>They acidify the lumen of specific organelles (D)</p> Signup and view all the answers

What is the mechanism of action for proton pump inhibitors?

<p>They block the H+/K+ ATPase system irreversibly (B)</p> Signup and view all the answers

What causes a decrease in the strength of heart muscle contractions when the intracellular Na+ concentration increases?

<p>Diminished activity of Na-Ca exchanger (A)</p> Signup and view all the answers

What is a potential therapeutic use of Na+/K+ ATPase inhibitors?

<p>Management of congestive heart failure (B)</p> Signup and view all the answers

What role do cardiac glycosides like Digitalis play in the treatment of heart conditions?

<p>They increase contractility of the heart muscle (C)</p> Signup and view all the answers

What is the rate limiting step in the de novo biosynthesis of pyrimidines?

<p>Formation of carbamoyl phosphate from glutamine (D)</p> Signup and view all the answers

Which enzyme catalyzes the joining of carbamoyl phosphate and aspartate in pyrimidine biosynthesis?

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

What role do ATP and CTP play in the activity of aspartate transcarbamoylase (ATCase)?

<p>ATP stimulates and CTP inhibits (D)</p> Signup and view all the answers

In de novo purine biosynthesis, which of the following is primarily synthesized from ribose-5-phosphate?

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

Which aspect of pyrimidine biosynthesis involves multiple active sites in the enzyme?

<p>Formation of carbamoyl phosphate (D)</p> Signup and view all the answers

Which enzyme is primarily responsible for the synthesis of deoxyribonucleotides from ribonucleotides?

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

Which nucleotide must be converted to deoxyuridine diphosphate before producing deoxythymidine triphosphate?

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

In the salvage pathway for pyrimidine nucleotides, which kinase is known for phosphorylating uridine?

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

Which of the following statements is NOT true regarding ribonucleotide reductase?

<p>It directly synthesizes thymidine nucleotides. (A)</p> Signup and view all the answers

What is the end product of the synthesis pathway starting with uridine monophosphate (UMP)?

<p>Deoxythymidine monophosphate (dTMP) (A)</p> Signup and view all the answers

What is the product of the decarboxylation of orotidylate?

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

Which enzyme is involved in the conversion of UMP to UTP?

<p>Nucleoside diphosphokinase (A), Nucleoside monophosphate kinase (D)</p> Signup and view all the answers

What role does CTP play in the regulation of pyrimidine biosynthesis?

<p>It serves as a feedback inhibitor of ATCase. (A)</p> Signup and view all the answers

Which of the following statements about salvaged pyrimidine bases is true?

<p>They do not have any phosphates. (D)</p> Signup and view all the answers

What is the initial component required to form a pyrimidine nucleotide?

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

Which of the following accurately describes the salvage pathway of pyrimidine nucleotides?

<p>They are formed without the need for phosphates. (B)</p> Signup and view all the answers

Which substrate is used in the synthesis of UTP from UMP?

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

What is the primary function of cytidine deaminase in pyrimidine metabolism?

<p>It converts cytidine to uridine. (B)</p> Signup and view all the answers

What distinguishes purines from pyrimidines in their molecular structure?

<p>Purines have a six-membered nitrogen ring fused to an imidazole ring. (D)</p> Signup and view all the answers

Which sugar component is found in RNA but not in DNA?

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

What is the role of the phosphate group in nucleotides?

<p>To link nucleotides together through a phosphodiester bond. (C)</p> Signup and view all the answers

Which of the following correctly matches a nitrogenous base with its classification?

<p>Thymine - Pyrimidine (D)</p> Signup and view all the answers

Which pathway for nucleotide synthesis involves recycling components from the breakdown of nucleic acids?

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

What type of linkage connects the phosphate group of one nucleotide to the sugar of the next nucleotide?

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

What suffix is used for purine bases in nucleoside nomenclature?

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

Which component is NOT a part of a nucleotide?

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

What are the two main pathways for nucleotide biosynthesis?

<p>De novo and salvage pathways (A)</p> Signup and view all the answers

Which of the following nucleotides is a precursor to both adenine and guanine?

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

What is the primary role of nucleotides in the cell?

<p>Serving as precursors for DNA and RNA (C)</p> Signup and view all the answers

Which nitrogenous base is present in RNA but not in DNA?

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

The synthesis of deoxyribonucleotides involves a conversion of which type of nucleotides?

<p>Ribonucleotides to deoxyribonucleotides (D)</p> Signup and view all the answers

Which processes are considered anabolic in nucleic acid metabolism?

<p>Biosynthesis of nucleotides (A)</p> Signup and view all the answers

Which nucleotide is involved in cellular signaling as a secondary messenger?

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

What is the significance of the pentose sugar in nucleotides?

<p>It forms the backbone of RNA or DNA (C)</p> Signup and view all the answers

What is the final product of purine nucleotide catabolism that is excreted in urine?

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

Which enzyme is critically important for purine salvage in rapidly dividing cells?

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

What is the first step in the degradation of guanosine?

<p>De-ribosylation (C)</p> Signup and view all the answers

What disorder is associated with a deficiency in the enzyme adenosine deaminase?

<p>Severe combined immunodeficiency (SCID) (B)</p> Signup and view all the answers

What is formed when dUTP is converted in the dUDP synthesis pathway?

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

Which enzyme's defects can lead to the condition known as gout?

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

Which deoxyribonucleotide is synthesized directly from dUMP?

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

What is a common symptom of infants suffering from severe combined immunodeficiency (SCID)?

<p>Severe and recurrent infections (A)</p> Signup and view all the answers

How does dATP affect the activity of ribonucleotide reductase?

<p>It inhibits the enzyme. (B)</p> Signup and view all the answers

What type of crystals are formed due to the excretion of uric acid?

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

Which enzyme is primarily responsible for converting ribonucleotides to deoxyribonucleotides?

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

What is the underlying genetic cause of Lesch-Nyhan syndrome?

<p>Defect in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (B)</p> Signup and view all the answers

Which purine nucleotides inhibit the synthesis of phosphoribosylamine from PRPP?

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

What effect does high concentration of purines have on pyrimidine biosynthesis?

<p>It stimulates pyrimidine synthesis. (C)</p> Signup and view all the answers

Which molecules regulate the selection of substrates in ribonucleotide reductase?

<p>ATP, dATP, dTTP, and dGTP (B)</p> Signup and view all the answers

What type of mechanism does ribonucleotide reductase employ to convert ribonucleotides?

<p>Free radical mechanism (A)</p> Signup and view all the answers

Which molecule serves as the source of sugar for purine nucleotides?

<p>Ribose 5-phosphate (D)</p> Signup and view all the answers

What feedback mechanism affects the enzyme catalyzed by glutamine-PRPP amidotransferase?

<p>Inhibited by AMP, ADP, and ATP (D)</p> Signup and view all the answers

Which amino acids contribute nitrogen atoms (N2) in purine biosynthesis?

<p>Glutamine, Aspartate, and Glycine (B)</p> Signup and view all the answers

What is the primary consequence of AMP feedback inhibition in purine synthesis?

<p>Inhibits AMP conversion from IMP (B)</p> Signup and view all the answers

How do salvage reactions benefit nucleotide synthesis?

<p>They provide nucleotides from breakdown products. (A)</p> Signup and view all the answers

Which of the following is true about the regulation of AMP and GMP synthesis from IMP?

<p>Both AMP and GMP provide feedback for their respective synthesis pathways. (A)</p> Signup and view all the answers

What role does PRPP play in purine nucleotide synthesis?

<p>It serves as a source of sugar and is essential for synthesizing purine nucleotides. (C)</p> Signup and view all the answers

What is a characteristic of the salvage pathway in nucleotide synthesis?

<p>It uses intermediates from nucleotide degradation to form nucleotides. (A)</p> Signup and view all the answers

What role does dATP play in the regulation of ribonucleotide reductase?

<p>It functions as a general inhibitor for all substrates. (A)</p> Signup and view all the answers

How does the binding of dTTP to ribonucleotide reductase affect nucleotide synthesis?

<p>It inhibits the formation of deoxypyrimidines. (D)</p> Signup and view all the answers

What condition is characterized by an elevation in serum uric acid concentration?

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

What is the primary consequence of increased uric acid levels in severe hyperuricemia?

<p>Deposits of uric acid crystals in soft tissues. (C)</p> Signup and view all the answers

Which enzyme defect is associated with Lesch-Nyhan syndrome?

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

Which of the following nucleotides would enhance the production of dUDP and dCDP when binding to the specificity site of ribonucleotide reductase?

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

What normal serum uric acid concentration range is established for adults?

<p>3-7 mg/dl (C)</p> Signup and view all the answers

What condition can result from a lack of feedback control of PRPP glutamylamidotransferase?

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

Flashcards

Peripheral membrane proteins

Proteins indirectly bound to the membrane via interactions with integral proteins or lipid head groups. They are located on either the cytosolic or exoplasmic face of the plasma membrane.

Integral membrane proteins

Proteins embedded within the lipid bilayer, often spanning the entire membrane.

Lipid-anchored proteins

Proteins attached to the membrane via a covalently attached lipid, with the lipid embedded in the bilayer. The protein itself doesn't enter the bilayer.

Transmembrane proteins

Proteins that span the entire width of a cell membrane.

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Transport proteins

Proteins that facilitate the movement of substances across the membrane.

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Membrane asymmetry

Different proteins and lipids are unevenly distributed across the two faces of the membrane.

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Cytoskeletal filaments

Filaments (proteins) loosely associated with the cytosolic face of the membrane, providing structural support and communication pathways.

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Single-pass transmembrane protein

Membrane protein that passes once across the membrane.

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Plasma Membrane Function

Maintains a stable internal environment (homeostasis) and facilitates cell communication via signal transduction and recognition.

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Fluid Mosaic Model

The plasma membrane is a flexible and dynamic structure composed of a phospholipid bilayer with embedded proteins, forming a semi-permeable barrier.

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Phospholipid Bilayer

Two layers of phospholipids, forming a barrier. Hydrophilic heads face outward, and hydrophobic tails inward.

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Amphipathic

Describes molecules with both hydrophilic (water-loving) and hydrophobic (water-fearing) regions.

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Membrane Permeability

The plasma membrane allows some substances to pass through but restricts others.

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Cell-cell recognition

Cells identify each other via specific proteins/carbohydrates on the cell surface. Crucial for immune response.

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Cholesterol in Membrane

Stiffens the membrane and affects fluidity.

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Phosphoglycerides

A type of lipid, a main component of the plasma membrane. Similar to glycerol 3-phosphate, with hydrophobic and hydrophilic regions

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Active Transport

Movement of molecules across a membrane from a low concentration to a high concentration, requiring energy.

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ATP-powered pumps

Proteins that use energy from ATP hydrolysis to move molecules across a membrane against their concentration gradient.

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Non-gated Ion Channels

Channels that are always open, allowing specific ions to move freely down their concentration gradient.

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Electrochemical Gradient

The combined influence of concentration gradient and membrane potential on the movement of charged molecules.

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Gated Ion Channels

Channels that open only in response to specific signals (chemical or electrical) allowing ion movement across the membrane.

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Uniporters

Transport proteins that move only one type of molecule down its concentration gradient.

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Facilitated Diffusion

Movement of molecules across a membrane with the help of transport proteins down their concentration gradient, without energy expenditure.

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Glucose Transporter GLUT1

A uniporter protein that transports glucose into cells down its concentration gradient.

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What is the function of membrane proteins in cell shape?

Membrane proteins can bind to cytoskeletal elements like microfilaments, providing structural support and stabilizing the location of certain membrane proteins, which ultimately helps maintain cell shape.

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ECM and Intracellular Changes

Proteins that bind to molecules in the extracellular matrix (ECM) can coordinate changes happening both inside and outside the cell.

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Plasma Membrane Barrier

The plasma membrane acts as a barrier, controlling what passes in and out of the cell.

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Plasma Membrane Permeability

The plasma membrane is highly permeable to water, but only weakly permeable to salts, small molecule sugars, and amino acids.

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Organelle Membranes

Each organelle has a unique membrane with specific proteins essential for its function.

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Osmosis

Osmosis describes the movement of water across a semipermeable membrane from a dilute solution (high water concentration) to a concentrated solution (low water concentration), aiming for an equal water concentration on both sides.

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Hypotonic Solution

When a cell is placed in a solution with a lower solute concentration than its interior, water flows into the cell, causing it to swell.

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Isotonic Solution

If a cell is placed in a solution with the same solute concentration as its interior, there's no net movement of water into or out of the cell.

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Na+/K+ ATPase: E1 to E2

During this transition, the Na+ ions bound to the pump become accessible to the outside of the cell (exoplasmic face). The pump's affinity for these Na+ ions decreases, allowing them to be released.

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Na+/K+ ATPase: E2 to E1

This transition brings in potassium ions (K+). Two K+ ions bind to the pump, which is now accessible to the inside of the cell (cytoplasmic face). After a conformational change, the pump releases the K+ ions into the cell.

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Na+/K+ ATPase: Role of Drugs

Certain drugs, like ouabain and digoxin, block the Na+/K+ pump by binding to its outside. This disrupts the normal balance of sodium and potassium in cells, highlighting the pump's importance.

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Na+/Glucose Symport: Location

This transport system is found in the small intestine, aiding in the absorption of glucose and sodium.

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Na+/Glucose Symport: Mechanism

The Na+/K+ pump creates a sodium gradient across the intestinal cell. This gradient powers the symporter, which moves both sodium and glucose into the cell against their concentration gradient.

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Digitalis effect on heart

Digitalis is a drug that increases the force of heart muscle contractions by inhibiting the dephosphorylation of Na+/K+ ATPase, leading to a higher concentration of sodium inside the cell. This ultimately results in higher intracellular calcium levels, enhancing contraction.

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Na+/Ca2+ Antiporter Function

The Na+/Ca2+ antiporter in cardiac muscle cells exports calcium ions out of the cell in exchange for sodium ions. This helps maintain low calcium levels in the cytosol, regulating muscle contraction.

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Digitalis and Congestive Heart Failure

Digitalis is used to treat congestive heart failure because it strengthens heart contractions by increasing intracellular calcium levels. This helps the heart pump more effectively.

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Ouabain Mechanism

Ouabain is a toxin that binds to the extracellular side of the Na+/K+ ATPase, preventing it from changing conformation. This leads to higher intracellular sodium levels, inhibiting the sodium-calcium exchanger and increasing calcium.

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V-Class Proton Pumps

V-class proton pumps are found in lysosomes, endosomes, and vacuoles. They actively transport hydrogen ions (H+) into these organelles, acidifying their lumen.

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Proton Pump Inhibitors

Proton pump inhibitors block the activity of H+/K+ ATPase, specifically in the stomach. This reduces acid production and promotes healing of ulcers.

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Carbamoyl Phosphate Synthetase II (CPS II)

The enzyme responsible for the rate-limiting step in pyrimidine biosynthesis, catalyzing the formation of carbamoyl phosphate from glutamine, CO2, and ATP.

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Aspartate Transcarbamoylase (ATCase)

The enzyme that joins carbamoyl phosphate and aspartate to form carbamoylaspartate in the second step of pyrimidine biosynthesis. It's regulated by CTP (inhibitor) and ATP (activator).

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What is the rate-limiting step in pyrimidine biosynthesis?

The formation of carbamoyl phosphate from glutamine, CO2, and ATP, catalyzed by carbamoyl phosphate synthetase II (CPS II), is the rate-limiting step.

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How is ATCase regulated?

ATCase is regulated by allosteric control. CTP, the end product of pyrimidine synthesis, inhibits ATCase activity, while ATP, a key energy molecule, activates it.

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What are the two main steps in de novo pyrimidine biosynthesis?

  1. Formation of carbamoyl phosphate from glutamine, CO2, and ATP (catalyzed by CPS II). 2. Joining of carbamoyl phosphate and aspartate to form carbamoylaspartate (catalyzed by ATCase).
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Deoxyribonucleotide

A nucleotide containing deoxyribose, forming the building blocks of DNA.

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Ribonucleotide Reductase

Enzyme converting ribonucleotides (like ADP) to deoxyribonucleotides (like dADP) for DNA synthesis.

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dTMP Synthesis

The complex pathway converting UMP to dTMP, involving several steps including ribonucleotide reductase and thymidylate synthase.

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Salvage Pathway

Reusing pre-existing pyrimidine bases to build new nucleotides, conserving energy.

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Kinase

An enzyme adding phosphate groups to molecules.

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Orotidylate (OMP)

A pyrimidine nucleotide formed when orotate is joined with phosphoribosylpyrophosphate (PRPP).

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Uridylate (UMP)

A pyrimidine nucleotide formed by the decarboxylation of orotidylate (OMP).

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PRPP (Phosphoribosylpyrophosphate)

A phosphorylated form of ribose that acts as a building block for nucleotide synthesis.

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What is the source of the sugar in pyrimidine nucleotides?

PRPP (phosphoribosylpyrophosphate) provides the sugar component, ribose, for pyrimidine nucleotides.

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What are the sources of nitrogen in pyrimidine biosynthesis?

Amino acids, specifically aspartate and glutamine, donate the nitrogen atoms required to form the pyrimidine ring.

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CTP (cytidine triphosphate)

A pyrimidine nucleotide synthesized from UTP. CTP acts as a feedback inhibitor of ATCase.

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What is the role of ATP in pyrimidine biosynthesis?

ATP acts as a positive regulator of ATCase, the enzyme responsible for the second step in pyrimidine biosynthesis.

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How is pyrimidine synthesis regulated?

Pyrimidine synthesis is regulated by feedback mechanisms. CTP inhibits ATCase, while ATP activates it, helping to maintain balance between purine and pyrimidine nucleotides.

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What is nucleic acid metabolism?

Nucleic acid metabolism encompasses the biosynthesis (creation) and breakdown (degradation) of nucleotides, the building blocks of DNA and RNA.

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De novo vs. Salvage Pathways

De novo pathways synthesize nucleotides from simple precursors, while salvage pathways recycle pre-existing bases.

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Purine Synthesis

Purine synthesis involves the de novo production of inosine monophosphate (IMP), which is a precursor for adenine and guanine.

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Pyrimidine Synthesis

Pyrimidine synthesis starts with the de novo production of uracil, then modified to form cytosine and thymine.

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What are deoxyribonucleotides?

Deoxyribonucleotides are nucleotides containing deoxyribose, the sugar found in DNA.

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Purine Degradation

Purine degradation leads to the production of uric acid, which is excreted in urine.

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Pyrimidine Degradation

Pyrimidine degradation produces simpler molecules that can be further used in metabolic pathways.

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Purines

Double-ring nitrogenous bases found in DNA and RNA. Examples include adenine (A) and guanine (G).

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Pyrimidines

Single-ring nitrogenous bases found in DNA and RNA. Examples include cytosine (C), thymine (T), and uracil (U).

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Nucleosides

A nitrogenous base linked to a sugar molecule (ribose or deoxyribose).

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Nucleotides

A nucleoside with a phosphate group attached. They are the building blocks of DNA and RNA

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De novo Pathway

The process of synthesizing nucleotides from scratch using simpler molecules.

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3’ - 5’ phosphodiester linkage

The chemical bond that connects nucleotides in DNA and RNA, involving the phosphate group on the 5’ carbon of one nucleotide and the hydroxyl group on the 3’ carbon of the next.

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What is the difference between DNA and RNA?

DNA has deoxyribose sugar and uses thymine (T) as a base. RNA has ribose sugar and uses uracil (U) as a base.

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Purine Catabolism

The breakdown of purine nucleotides, ultimately producing uric acid which is excreted in urine.

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Adenosine Deaminase (ADA)

A key enzyme in purine salvage pathways, especially crucial in rapidly dividing cells. It converts adenosine to inosine.

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Severe Combined Immunodeficiency (SCID)

A rare genetic disorder caused by defects in immune cells. It results from deficiencies in enzymes like ADA.

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Uric Acid Build-up

Excess uric acid in the body can lead to conditions like gout, a painful inflammatory disease affecting joints.

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Gout

A common inflammatory condition caused by the build-up of uric acid crystals in joints, leading to pain and swelling.

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Lesch-Nyhan Syndrome

A rare genetic disorder primarily affecting males. It's linked to a deficiency in HGPRT, an enzyme essential for purine salvage.

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Purine Salvage

The process of reusing pre-existing purine bases to build new nucleotides, saving energy and resources.

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HGPRT Deficiency

A deficiency in HGPRT (hypoxanthine-guanine phosphoribosyltransferase) leads to Lesch-Nyhan syndrome, a severe genetic disorder.

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Thymidylate Synthase

Enzyme that adds a methyl group to dUMP to form dTMP (thymine nucleotide).

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Deoxyribonucleotide Biosynthesis

The process of creating deoxyribonucleotides, essential building blocks for DNA, from ribonucleotides.

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Regulation of Nucleotide Biosynthesis: Purines

The synthesis of purines, like adenine and guanine, is regulated by feedback inhibition, where an excess of purine nucleotides inhibits further synthesis.

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Regulation of Nucleotide Biosynthesis: Pyrimidines

The synthesis of pyrimidines, like cytosine and thymine, is regulated by feedback inhibition, where an excess of pyrimidine nucleotides turns off de novo synthesis, while an excess of purines stimulates it, keeping them balanced.

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ATCase Feedback Inhibition

The enzyme aspartate transcarbamoylase (ATCase) is inhibited by CTP (pyrimidine end product) and activated by ATP (purine end product), regulating the second step of pyrimidine biosynthesis.

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dUDP to dUMP

The conversion of dUDP to dUMP is a crucial step in thymidine nucleotide synthesis, removing the phosphate group.

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dUMP to dTMP

The conversion of dUMP to dTMP is catalyzed by thymidylate synthase, adding a methyl group to create the thymine nucleotide.

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PRPP

Phosphoribosylpyrophosphate (PRPP) is a molecule that serves as the source of the sugar (ribose) for purine nucleotides. It's synthesized from ribose 5-phosphate, which comes from the pentose phosphate pathway.

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Purine Synthesis: Nitrogen Sources

The nitrogen atoms in purine nucleotides come from amino acids. Glutamine provides two nitrogen atoms, aspartate provides one, and glycine contributes one.

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Branch Point in Purine Synthesis

Inosine 5'-monophosphate (IMP) is a key intermediate in purine synthesis. It acts as a branch point, leading to the production of either AMP (adenosine monophosphate) or GMP (guanosine monophosphate).

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Regulation of Purine Synthesis

Purine synthesis is regulated by feedback inhibition and feed-forward activation. Purine nucleotides (AMP, GMP) inhibit PRPP synthetase, while PRPP itself stimulates the enzyme. Also, ATP stimulates the conversion of IMP to GMP, while GTP stimulates the conversion of IMP to AMP.

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AMP

Adenosine monophosphate (AMP) is a purine nucleotide that is a building block of RNA and a key intermediate in energy metabolism. It is also involved in signal transduction pathways.

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dATP regulation

dATP is a general inhibitor of ribonucleotide reductase, acting as a signal that there are enough deoxyribonucleotides, while ATP activates the enzyme, promoting DNA synthesis.

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Specificity site

A region on ribonucleotide reductase where nucleotides bind, influencing the enzyme's preference for different substrates to maintain a balance of deoxyribonucleotides.

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Hyperuricemia

Elevated levels of uric acid in the blood, often associated with increased uric acid excretion.

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Purine salvage pathway

Metabolic pathway that recycles pre-existing purine bases (hypoxanthine and guanine), preventing them from being degraded and conserving energy.

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PRPP glutamylamidotransferase

An enzyme involved in purine biosynthesis that lacks feedback control, leading to overproduction of purine nucleotides.

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Study Notes

Biomembranes: Structure and Transport Mechanisms

  • Biomembranes are composed of lipids and proteins
  • The composition and structure of a membrane determine its physical characteristics
  • Membranes separate compartments inside and outside cells, and between intracellular compartments
  • Membranes act as a permeability barrier
  • Membranes regulate the exchange of substances to maintain a steady internal environment
  • Membranes enable cells to signal and communicate to other cells

Learning Outcomes

  • Describe the fluid-mosaic model of membrane structure
  • List various lipid and protein types in the membrane and their functions
  • Predict the movement of molecules in diffusion and osmosis
  • Explain how molecules/ions enter and leave cells
  • Describe and explain specific examples of membrane transport
  • Explain how combinations of transport proteins enable cells to perform essential functions

Membrane Structure: Prokaryotes

  • Prokaryotic cells have a plasma membrane, without any internal membrane-bound compartments

Membrane Structure: Eukaryotes

  • Eukaryotic cells are partitioned into smaller organelles (nucleus being the largest)
  • Each organelle usually has one or more biomembranes
  • Biomembranes in organelles carry out specific cellular functions

CELL ARCHITECTURE: Structure: Triacylglyceride

  • Triacylglycerols are composed of glycerol attached to three fatty acids.

CELL ARCHITECTURE: Structure of Biomembranes

  • Biomembranes are primarily composed of phospholipids
  • Phospholipids are amphipathic with a hydrophilic head and hydrophobic tails.

Structure of Biomembranes: Phospholipids

  • Phospholipids are amphipathic molecules.
  • Phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol are important examples of phospholipids.

Structure of Biomembranes: Phospholipid

  • Phospholipids arrange themselves in a bilayer structure:
    • Polar heads face outward towards the aqueous environment.
    • Nonpolar tails form the inner hydrophobic core.

Plasma membranes: Functions

  • The lipid and proteins composition of a membrane determines its physical characteristics and functional properties
  • They isolate the cytoplasm from the external environment (acts as a permeability barrier).
  • They regulate the exchange of substances (helps the cell and organism maintain a steady internal environment).
  • They facilitate communication with other cells (signal transduction).
  • They also facilitate cell-to-cell recognition

Cellular membrane

  • The fluid-mosaic model describes membrane structure and considers the fluidity and mosaic nature of the membrane.

Cellular membranes are fluid mosaics of lipids and proteins

  • The fluid mosaic model describes the arrangement of lipids and proteins in the membrane, highlighting the membrane's fluidity and mosaic features.

Components of the Plasma Membrane

  • Phospholipids have a hydrophilic head and hydrophobic tails, creating a barrier.
  • Cholesterol plays a role in stiffening by connecting phospholipids
  • Glycolipids are signal molecules
  • Glycoproteins have sugar chains (like antibodies) for cell-cell recognition

Biomembranes: Lipid Composition and Structural Organisation

  • Phospholipids spontaneously form a sheet-like phospholipid bilayer in cells.
  • The hydrocarbon tails of the phospholipids within each layer (leaflet) form a hydrophobic core in the membrane.

The Lipid Bilayer

  • The hydrophobic core of the lipid bilayer acts as a barrier, preventing the diffusion of water-soluble solutes.
  • Hydrophobic and van der Waals interactions maintain the stability of the bilayer structure

Three Classes of Lipids in Biomembranes

  • Biomembranes are composed of phosphoglycerides, sphingolipids, and steroids (like cholesterol).
  • All these lipid classes are amphipathic, with a polar head group and a hydrophobic tail.

Phosphoglycerides

  • Phosphoglycerides are derivatives of glycerol-3-phosphate.
  • A typical phosphoglyceride consists of two fatty acyl chains esterified to the glycerol phosphate and a polar head group attached to the phosphate group.

Sphingolipids

  • Sphingolipids are derived from sphingosine, an amino alcohol with a long hydrocarbon chain.
  • Sphingolipids contain a long-chain fatty acid attached to the sphingosine amino group.
  • Sphingomyelin is an example of an abundant sphingolipid.

Steroids: Cholesterol

  • Steroids have a four-ring hydrocarbon structure
  • Cholesterol is amphipathic because its hydroxyl group can interact with water.

Lipid Composition Influences the Physical Properties of Membranes

  • Lipid composition affects membrane properties
  • Lipid composition influences membrane specialization
  • Membrane fluidity depends on the lipid composition and temperature.

Lipid Composition of Membranes

  • Different membranes have different lipid compositions.
  • These differences in lipid composition often correspond to specializations of membrane functions like maintaining a particular fluidity that best suits the function.

Membrane fluidity

  • Membrane fluidity depends on the lipid composition and temperature.

Factors that affect membrane fluidity

  • Temperature affects membrane fluidity
  • Unsaturated hydrocarbon chains in phospholipids maintain membrane fluidity at lower temperatures.

Membrane Lipids Are Distributed Unequally in the Exoplasmic and Cytosolic Leaflets

  • There is an asymmetry in lipid composition across the bilayer.

Biomembranes: Protein Components and Basic Functions

  • Membrane proteins are the "mosaic" part of the membrane.
  • Membrane proteins are defined by their location within or on the surface of the membrane
  • The amount of proteins associated with biomembranes varies

Protein Domains- Exoplasmic

  • Protein domains on the extracellular surface typically bind to other molecules.
  • Some domains bind to signaling proteins, ions, and small metabolites

Protein Domains- Cytosolic

  • Cytosolic protein domains often form channels/pores for molecular movement
  • Some domains anchor the cytoskeleton or trigger intracellular signaling

Proteins Interact with Membranes in Three Different Ways

  • Membrane proteins are classified into integral, lipid-anchored, and peripheral based on their relationship with the membrane.

Integral membrane proteins

  • Integral proteins span the entire phospholipid bilayer.
  • Their hydrophilic parts interact with aqueous solutions.

Integral membrane proteins cont. 

  • Most transmembrane proteins embedded in the membrane are glycosylated.

Lipid-anchored membrane proteins

  • Lipid-anchored proteins are covalently bound to lipid molecules.

Peripheral membrane proteins

  • Peripheral proteins are indirectly bound to the membrane or interact with integral proteins or lipid head groups
  • Peripheral proteins tend to be localized on either the cytosolic or exoplasmic face.

Cytoskeletal Filaments

  • Cytoskeletal filaments are loosely associated with the membrane through peripheral proteins that maintain shape and cell structure.

Secondary Structures in Transmembrane Proteins

  • Single-pass transmembrane proteins contain a single membrane-spanning alpha-helix.
  • Multi-pass transmembrane proteins contain multiple membrane-spanning alpha-helices.

Transport Across Membranes

Passive Transport: Diffusion

  • Simple diffusion allows small molecules across the membrane down their concentration gradients.
  • Facilitated diffusion uses membrane proteins to speed up diffusion of larger molecules unable to cross the membrane unaided.

Active Transport

  • Active transport moves molecules against their concentration gradients.
  • It uses energy (such as from ATP hydrolysis).

Transport: Non-gated Ion Channels

  • Non-gated ion channels are open much of the time.

Non-gated Ion Channels

  • The inside of the plasma membrane has a negative electric potential (voltage).
  • Non-gated channels tend to be open much of the time and allow movement of specific ions.

Transporters: Carriers & Channels

  • Uniporters transport a single substrate.
  • Symporters transport two or more molecules in the same direction,.
  • Antiporters transport two or more molecules in opposite directions

Uniporter: Glucose Transporter GLUT1

  • GLUT1 is a uniporter that moves glucose into cells.
  • The concentration of glucose is generally higher in the blood than in the cell, driving glucose into the cell.

Co-Transporters: Antiporters and Symporters

  • Symporters move two or more molecules in the same direction.
  • Antiporters move two or more molecules in the opposite directions.
  • Their movement is often coupled to the movement of a different molecule (like an ion) that is moving down its concentration gradient

Co-transport by Symporters and Antiporters

  • This mechanism allows the movement of substances that are generally not easily transported

SUMMARY - through the cell membrane

  • Passive and Active transport types exist.

TRANSPORT SUMMARY

  • Summary about different transport methods (simple, facilitated, and active transports).

TRANSPORT ACROSS MEMBRANES: ACTIVE TRANSPORT MECHANISMS

  • These proteins are called ATPases; they normally do not hydrolyze ATP into ADP and Pi unless ions or other molecules are simultaneously transported.

Different Classes of Pumps Exhibit Characteristic Structural and Functional Properties

  • P, V, F, and ABC classes of ATP-powered pumps exist.
  • The types of molecules transported differs by class

ATP-Powered Pumps: P-class

  • Na+/K+ ATPase, Ca2+ ATPases, and H+/K+ ATPase pumps are examples of P-class pumps.
  • They are involved in maintaining ionic gradients within cells.

ATP-Powered Pumps: P-class (cont.)

  • Ca2+ ATPases have different cellular roles depending on location (muscle cell, etc.)

ATP-Powered Pumps: P-class (cont.)

ATP-Powered Pumps: F-class & V-class

  • F and V class pumps have structural similarities but function differently.
  • V-class pumps maintain low pH in intracellular organelles

H+ Proton pump

  • ATPases transport H+ against a gradient in several different cellular locations.

ATP-Powered Pumps: F-class

ATP-Powered Pumps: F-class - mitochondria

ATP-Powered Pumps: F-class - chloroplast

  • F-class proton pumps are also known as ATP synthases in mitochondria and chloroplasts

ATP-Powered Pumps: ABC-superfamily

  • The ABC superfamily is a large and diverse group of transmembrane proteins that transport a variety of molecules

ATP-Powered Pumps: ABC-superfamily (cont.)

  • ABC proteins have a structural organization that is quite different.

ATP-Powered Pumps: ABC-superfamily (cont.)

Ca2+ ATPase Transporter

  • SERCA pumps are examples of Ca2+ ATPases

Ca2+ ATPase Pumps Ca2+ lons from the Cytosol into the Sarcoplasmic Reticulum

  • Ca2+ homeostasis is crucial in skeletal muscle contraction and relaxation.

Mechanism of Action of the Ca2+ ATPase: Step 1

Mechanism of action of the Ca2+ ATPase: Step 2

Mechanism of action of the Ca2+ ATPase: Step 3

Mechanism of action of the Ca2+ ATPase: Step 4

Mechanism of action of the Ca2+ ATPase: Step 5

Mechanism of action of the Ca2+ ATPase: Step 6

P-class ion pumps

  • All P-class ion pumps are phosphorylated
  • Operate in similar ways
  • P-class pumps include Na+/K+ ATPase, H+/K+ ATPase, and Ca2+ ATPase pumps

Na+/K+ ATPase Transporter

  • Na+/K+ ATPase is an antiport pump
  • It is responsible for maintaining internal Na+ and K+ ion concentration in animal cells.

Na+/K+ ATPase Maintains the Intracellular Na + and K + Concentrations

  • Na+/K+ ATPase is vital for maintaining specific ion concentrations in cells.
  • The structure and role of the Na+/K+ pump are important factors to consider

Na+/K+ ATPase

  • Na+/K+ ATPase moves ions against their concentration gradients.
  • It requires ATP to achieve proper movement direction.

Mechanism of action of the Na+/K+ ATPase (cont.)

Mechanism of action of the Na+/K+ ATPase (cont.)

Mechanism of action of the Na+/K+ ATPase (cont.)

Mechanism of action of the Na+/K+ ATPase (cont.)

Mechanism of action of the Na+/K+ ATPase (cont.)

Mechanism of action of the Na+/K+ ATPase (cont.)

Mechanism of action of the Na+/K+ ATPase (cont.)

Mechanism of action of the Na+/K+ ATPase (cont.)

Mechanism of action of the Na+/K+ ATPase (cont.)

Mechanism of action of the Na+/K+ ATPase

  • Specific drugs can interfere with the Na+/K+ pump

Na+/Glucose Symport

  • Na+ and glucose are co-transported into cells.

Na+/Glucose Symport (cont.)

  • The Na+ gradient drives glucose transport
  • The Na+/K+ pump maintains the Na+ gradient crucial for this process.

Na+/Glucose Symport (cont.)

  • Glucose is transported against its concentration gradient using the Na+ gradient

Inhibitors of the Na+/K+ Pump: Digitalis

  • Digitalis inhibits the Na+/K+ pump, which can impact calcium levels and the strength of heart contractions.

Na+-Linked Antiporter Exports Ca2+ from Cardiac Muscle Cells

  • Na+/Ca2+ antiporters regulate Ca2+ homeostasis in cardiac muscle cells.

Na+-Linked Antiporter Exports Ca2+ from Cardiac Muscle Cells (cont.)

Na+-Linked Antiporter Exports Ca2+ from Cardiac Muscle Cells (cont.)

Inhibitors of the Na+/K+ Pump: Ouabain

  • Ouabain blocks the Na+/K+ pump by binding to a specific area in the pump protein.

H+ ATPases Transporter

V-Class H+ ATPases Pump Protons Across Lysosomal and Vacuolar Membranes

Inhibitors of H+ ATPases Pump

  • Proton pump inhibitors are useful against excessive stomach acid caused by ulcers.

ABC- superfamily Transporters

ABC Transporters

ABC Transporters (cont.)

ABC Transporters

ABC Transporters

ABC Transporters

ABC Transporters: CFTR

ABC Transporters- MDR proteins

ABC Transporters

ABC Transporters- Blood-brain Barrier

Causes of defects in ABC Transporters

Additional Resources

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Description

Explore the essential functions and characteristics of the plasma membrane in this quiz. Delve into topics such as lipid bilayer formation, membrane proteins, and cell recognition. Test your understanding of cholesterol's role, glycolipids, and the stability of the membrane structure.

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