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Questions and Answers
What are examples of common fibrous proteins found in the extracellular matrix?
What are examples of common fibrous proteins found in the extracellular matrix?
What structural form do typical collagen molecules take?
What structural form do typical collagen molecules take?
Triple helix
Which type of collagen is associated with high tensile strength in tendons and the cornea?
Which type of collagen is associated with high tensile strength in tendons and the cornea?
Which collagen types form a three-dimensional mesh instead of distinct fibrils?
Which collagen types form a three-dimensional mesh instead of distinct fibrils?
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What amino acids are collagen particularly rich in?
What amino acids are collagen particularly rich in?
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Glycine is found in every third position of the polypeptide chain in collagen.
Glycine is found in every third position of the polypeptide chain in collagen.
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What is the main role of α1-antitrypsin in elastin degradation?
What is the main role of α1-antitrypsin in elastin degradation?
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What genetic disorder is characterized by brittle bones and is associated with defects in type I collagen?
What genetic disorder is characterized by brittle bones and is associated with defects in type I collagen?
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What is the effect of a deficiency in vitamin C on collagen synthesis?
What is the effect of a deficiency in vitamin C on collagen synthesis?
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Which one of the following etiologies most likely explains the pulmonary symptoms of a 30-year-old woman of Northern European ancestry with a family history of lung problems?
Which one of the following etiologies most likely explains the pulmonary symptoms of a 30-year-old woman of Northern European ancestry with a family history of lung problems?
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What is the result of dysfunctional lysyl oxidase in connective tissue?
What is the result of dysfunctional lysyl oxidase in connective tissue?
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What is the differential basis of the liver and lung pathology seen in α1-antitrypsin deficiency?
What is the differential basis of the liver and lung pathology seen in α1-antitrypsin deficiency?
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Which type of collagen is particularly important in the basement membranes?
Which type of collagen is particularly important in the basement membranes?
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Which pairing of a defective (or deficient) molecule and the resulting pathology best fits a child who has fractures and thin bones?
Which pairing of a defective (or deficient) molecule and the resulting pathology best fits a child who has fractures and thin bones?
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How and why is proline hydroxylated in collagen?
How and why is proline hydroxylated in collagen?
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What are the six major classes of enzymes?
What are the six major classes of enzymes?
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Enzymes are consumed during the reaction they catalyze.
Enzymes are consumed during the reaction they catalyze.
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The active site of an enzyme is a special pocket or cleft formed by the _____ of the protein.
The active site of an enzyme is a special pocket or cleft formed by the _____ of the protein.
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What significantly increases the catalytic efficiency of enzymes?
What significantly increases the catalytic efficiency of enzymes?
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What type of inhibition is caused by ethanol in the treatment of ethylene glycol poisoning?
What type of inhibition is caused by ethanol in the treatment of ethylene glycol poisoning?
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In the reaction catalyzed by alcohol dehydrogenase (ADH), NAD+ functions as a(n):
In the reaction catalyzed by alcohol dehydrogenase (ADH), NAD+ functions as a(n):
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What do enzymes provide to chemical reactions?
What do enzymes provide to chemical reactions?
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What is the primary function of protein kinases?
What is the primary function of protein kinases?
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What happens to enzyme synthesis during high blood glucose levels?
What happens to enzyme synthesis during high blood glucose levels?
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Cells can only regulate enzyme activity, not enzyme synthesis.
Cells can only regulate enzyme activity, not enzyme synthesis.
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What does the maximal velocity (Vmax) represent in enzyme reactions?
What does the maximal velocity (Vmax) represent in enzyme reactions?
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What kind of curve do most enzymes show according to Michaelis-Menten kinetics?
What kind of curve do most enzymes show according to Michaelis-Menten kinetics?
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What happens to reaction velocity as temperature increases until a peak velocity is reached?
What happens to reaction velocity as temperature increases until a peak velocity is reached?
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What is the optimum temperature range for most human enzymes?
What is the optimum temperature range for most human enzymes?
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Which of the following statements about pH effects on enzymes is true?
Which of the following statements about pH effects on enzymes is true?
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What does Km (Michaelis constant) indicate about an enzyme?
What does Km (Michaelis constant) indicate about an enzyme?
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The presence of a competitive inhibitor decreases the apparent Km for a given substrate.
The presence of a competitive inhibitor decreases the apparent Km for a given substrate.
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What is the primary method by which many enzymes are regulated?
What is the primary method by which many enzymes are regulated?
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Match the following types of inhibition with their effects:
Match the following types of inhibition with their effects:
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What is the effect of noncompetitive inhibitors on the Lineweaver-Burk plot?
What is the effect of noncompetitive inhibitors on the Lineweaver-Burk plot?
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Which of the following drug classes acts as competitive inhibitors in cholesterol biosynthesis?
Which of the following drug classes acts as competitive inhibitors in cholesterol biosynthesis?
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Allosteric enzymes typically show a hyperbolic curve when velocity is plotted against substrate concentration.
Allosteric enzymes typically show a hyperbolic curve when velocity is plotted against substrate concentration.
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Study Notes
Overview of Fibrous Proteins
- Collagen and elastin are key fibrous proteins located in the extracellular matrix, essential for structural integrity in the body.
- Found in skin, connective tissues, blood vessel walls, and parts of the eye like sclera and cornea.
- Fibrous proteins exhibit mechanical properties due to their unique structures, contrasting with the complex shapes of globular proteins.
Collagen
- Most abundant protein in the human body, consisting of a triple helix formed by three polypeptide chains (α chains).
- Types of collagen vary in organization and function, influencing their roles in different tissues (e.g., dispersed in gel for support, bundled for strength).
- Type I collagen is predominantly found in tendons and cornea; Type II is restricted to cartilage.
Types of Collagen
- Fibril-forming Collagens: Types I, II, III; characterized by tensile strength, with I in tendons and III in blood vessels.
- Network-forming Collagens: Types IV and VIII; form a mesh for supportive structures, crucial in basement membranes.
- Fibril-associated Collagens: Types IX and XII; link collagen fibrils together enhancing the structure of the matrix.
Structure
- Amino Acid Composition: Rich in proline and glycine; repetitive sequence of –Gly–X–Y–, with proline contributing to structural kinks.
- Triple-helix Formation: Stabilized by interchain hydrogen bonds, forming elongated structures.
- Posttranslational Modifications: Hydroxylation of proline/lysine leads to hydroxyproline and hydroxylysine, enhancing stability; glycosylation of hydroxylysines occurs before helix formation.
Biosynthesis
- Collagen synthesis occurs in fibroblasts, osteoblasts, and chondroblasts, involving precursor formation, enzymatic modifications, and secretion.
- Hydroxylation: Requires molecular oxygen, iron, and vitamin C; deficiency leads to impaired collagen stability and associated conditions like scurvy.
- Assembly and Cross-linking: Involves the formation of procollagen, its secretion, N- and C-terminal processing, and cross-linking by lysyl oxidase to form mature collagen fibers.
Degradation and Diseases
- Collagen has a long half-life; typical turnover is through collagenases, with specific cleavage yielding fragments.
- Collagenopathies arise from defects in synthesis, including:
- Ehlers-Danlos Syndrome: Characterized by skin fragility and joint hypermobility; caused by collagen metabolism defects.
- Osteogenesis Imperfecta: Results in brittle bones due to mutations affecting type I collagen; severity ranges from mild to lethal forms.
Elastin
- Connective tissue protein with rubber-like properties, providing elasticity in tissues like lungs and blood vessel walls.
- Composed of tropoelastin, rich in small, nonpolar amino acids; limited hydroxyproline and hydroxylysine content.
Structure and Function
- Desmosine Cross-links: Formed through oxidative deamination of lysyl residues leading to an elastic network that allows stretching and recoil.
- Mutations in fibrillin-1 can lead to Marfan syndrome, affecting structural integrity across multiple body systems.
Role of α1-Antitrypsin
- Protein present in blood that inhibits proteolytic enzymes like neutrophil elastase, preventing degradation of elastin and other structural proteins.
- Emphysema Connection: A deficiency in α1-antitrypsin results in unmanaged activity of elastase, leading to destruction of alveolar elastic fibers.
- Genetic mutations, particularly in individuals of Northern European ancestry, may cause liver cirrhosis due to excess polymerization of AAT inside hepatocytes, placing individuals at risk for emphysema.### Smoking and Alpha-1 Antitrypsin (AAT) Deficiency
- Smoking induces oxidation of methionine, impairing the function of AAT, an elastase inhibitor.
- Smokers with AAT deficiency exhibit heightened lung damage and reduce survival rates compared to non-smokers with the same deficiency.
- Weekly intravenous administration of AAT can restore elastase inhibition, reaching therapeutic levels in lung epithelial fluid.
Collagen and Elastin
- Collagen and elastin are crucial fibrous proteins; collagen comprises proline, lysine, glycine, hydroxyproline, hydroxylysine, and glycosylated hydroxylysine.
- Collagen forms a triple-stranded helical structure, resulting in stiff fibrils, while other collagen types create mesh-like networks.
- Elastin possesses rubber-like properties essential for the elasticity of connective tissues, including the lungs.
- AAT primarily produced by the liver prevents the degradation of elastin by elastase; AAT deficiency can lead to emphysema and liver cirrhosis.
Clinical Cases Related to AAT Deficiency
- A 30-year-old woman with progressive dyspnea and no smoking history likely suffers from AAT deficiency, which causes pulmonary damage.
- Liver cirrhosis linked to AAT deficiency results from the polymerization and retention of AAT in the liver, while lung damage arises from unopposed elastase activity.
- A 7-month-old child with multiple fractures and blue sclerae suggests osteogenesis imperfecta, often caused by defects in type I collagen.
Proline Hydroxylation in Collagen
- Hydroxylation of proline occurs via prolyl hydroxylase in the rough endoplasmic reticulum and requires oxygen, iron, and vitamin C.
- Hydroxylation enhances hydrogen bonding, strengthening collagen's triple helix structure; vitamin C deficiency impairs this process.
Enzyme Function Overview
- Enzymes serve as catalysts to accelerate biochemical reactions without being consumed.
- They channel substrates into metabolic pathways and are crucial for maintaining reaction velocities.
Enzyme Nomenclature
- Enzymes are classified by two names: a common short name typically ending in "-ase" and a systematic name describing the reaction.
- Systematic names consist of six major enzyme classes, detailing the catalyzed chemical reactions.
Characteristics of Enzymes
- Active Sites: Formed by protein folding, these sites bind substrates, leading to catalysis.
- Catalytic Efficiency: Elevated reaction rates, typically 10^3 to 10^8 times faster than uncatalyzed reactions.
- Specificity: Enzymes interact with a limited number of substrates, facilitating specific reactions.
- Holoenzymes & Cofactors: Holoenzymes are active enzymes including non-protein components. Apoenzymes lack these components and require cofactors (metal ions) or coenzymes (organic molecules) for activity.
Factors Affecting Enzyme Activity
- Substrate Concentration: Reaction velocity increases with substrate concentration until a maximum rate (Vmax) is reached.
- Temperature: Enhances reaction velocity up to a peak before causing denaturation at high temperatures.
- pH Levels: Affect ionization at active sites; extreme pH values can lead to enzyme denaturation.
Michaelis-Menten Kinetics
- Describes enzyme kinetics where an enzyme forms a reversible ES complex with a substrate, which then leads to product formation.
Catalysis Mechanism
- Energy Changes: Enzymes lower the free energy of activation, facilitating faster reactions.
- Transition-State Stabilization: Enzymes stabilize the transition state, enhancing substrate conversion to product.
- Chemical Mechanisms: Include acid-base catalysis and covalent enzyme-substrate complexes to accelerate reactions.### Enzyme-Substrate Interaction Model
- S represents the substrate, E is the enzyme, ES is the enzyme-substrate complex, P is the product.
- Reaction rate constants are defined as k1, k-1, and k2.
Michaelis-Menten Equation
- Describes the relationship between reaction velocity (Vo) and substrate concentration ([S]).
- Vmax indicates the maximal reaction velocity.
- Km, the Michaelis constant, is calculated as (k-1 + k2)/k1 and represents the substrate concentration at which Vo = 1/2 Vmax.
- Assumptions include high substrate concentration relative to enzyme concentration and steady-state concentration of the ES complex.
Important Characteristics of Km
- Km reflects the affinity of the enzyme for its substrate.
- A small Km indicates high affinity, whereas a large Km indicates low affinity.
- Km remains constant irrespective of enzyme concentration.
Reaction Rate and Enzyme Concentration
- Reaction rate is directly proportional to enzyme concentration across varying substrate concentrations.
- Halving enzyme concentration results in halved initial reaction velocity (Vo) and Vmax.
Reaction Order
- When [S] is much lower than Km, reaction velocity is first-order relative to substrate concentration.
- When [S] is much higher than Km, velocity plateaus at Vmax, indicating zero-order reaction characteristics with respect to substrate concentration.
Lineweaver-Burk Plot
- Plotting 1/Vo versus 1/[S] yields a straight line to determine Km and Vmax.
- The x-intercept equals -1/Km and y-intercept equals 1/Vmax.
Enzyme Inhibition
- Inhibitors decrease enzyme reaction velocity and can be reversible or irreversible.
- Irreversible inhibitors form covalent bonds with enzymes, while reversible inhibitors bind non-covalently.
Competitive Inhibition
- Involves inhibitors binding to the active site, competing with the substrate.
- Increasing substrate concentration can overcome competitive inhibition; Vmax remains unchanged.
- Km increases in the presence of a competitive inhibitor, requiring more substrate for 1/2 Vmax.
Noncompetitive Inhibition
- Inhibitors bind to different sites on the enzyme, affecting Vmax without altering Km.
- Noncompetitive inhibition cannot be reversed by increasing substrate concentration.
Drugs and Competitive Inhibitors
- Statins, like atorvastatin and pravastatin, competitively inhibit HMG-CoA reductase, reducing cholesterol biosynthesis.
Regulation of Enzyme Activity
- Enzyme activity is regulated by changes in substrate concentration, allosteric effectors, covalent modification, and enzyme synthesis or degradation.
- Allosteric enzymes are affected by noncovalent binding of effectors at regulatory sites, altering enzyme affinity or activity.
Covalent Modification of Enzymes
- Enzyme activity can be regulated through phosphorylation, mediated by protein kinases and phosphatases.
- Phosphorylation can increase or decrease enzyme activity depending on the specific enzyme and context.
Enzyme Synthesis Regulation
- Cells can regulate enzyme quantities by inducing or repressing enzyme synthesis.
- Changes in enzyme levels occur more slowly than allosteric or covalent modifications.
Clinical Diagnosis Involving Enzymes
- Plasma enzymes indicate tissue damage; increased levels correlate with specific diseases like liver or heart issues.
- Isoenzymes differ in structure and function, assisting in identifying tissue damage through their specific patterns in plasma.
Isoenzymes and Myocardial Infarction
- Isoenzymes arise from genetic variations and can be separated via electrophoresis.
- Creatine kinase (CK) isoenzymes are key in diagnosing myocardial infarction, showing distinct compositions (CK1 = BB, CK2 = MB, CK3 = MM).
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Description
This quiz covers the essential characteristics and functions of fibrous proteins, specifically collagen and elastin. It discusses their roles in the extracellular matrix, contributions to various body structures, and their unique mechanical properties. Test your knowledge on these critical proteins and their significance in biological systems.
