Video Lecture Notes: Amino Acids, Peptides, Polypeptides, and Proteins

Amino Acids, Peptides, and Polypeptides

  • Anything over 40 amino acids is considered a protein.

  • Peptide bond: the bond between amino acids.

  • N terminus: corresponds to the 5' end of DNA and RNA.

  • C terminus: corresponds to the 3' end of DNA and RNA.

Enkephalins: Pentapeptides as Painkillers

  • Enkephalins are pentapeptides, meaning they consist of five amino acids.

  • Function: they signal to the brain and act as painkillers.

  • Mechanism: they bind to pain receptors, preventing stimuli transmission from nerve to nerve.

  • Runner's High: Enkephalins bind to pain receptors in the brain, reducing pain and fatigue and inducing euphoria after long runs.

Peptide Hormones: Oxytocin and Vasopressin

  • Oxytocin

    • Nine amino acid peptide (nonapeptide).

    • Produced by the posterior pituitary gland.

    • Functions:

      • Stimulates uterine contractions (used to induce labor).

      • Helps shrink the uterus back to normal size post-birth.

      • Signals to the breasts to contract, facilitating lactation.

  • Vasopressin

    • Antidiuretic hormone; nine amino acids in length.

    • Produced by the posterior pituitary gland.

    • Function:

      • Signals to the kidneys to retain fluid, reducing urine output and preventing dehydration.

Proteins: Polypeptides with Secondary Structures

  • Proteins are polypeptides greater than 40 amino acids in length that adopt secondary structures.

  • Two main types:

    • Fibrous proteins

    • Globular proteins

Fibrous Proteins

  • Long, linear proteins that wrap around each other (like a French braid).

  • Water insoluble; essential for structural components.

  • Examples:

    • Keratin

    • Alpha-keratin

    • Collagen

Globular Proteins

  • Compact, tangled structures.

  • Water soluble, allowing them to move throughout the body.

  • Examples:

    • Hemoglobin

    • Myoglobin

Protein Shape and Function

  • Every protein has a unique three-dimensional shape that dictates its function.

  • Fibrous proteins are long and water-insoluble.

  • Globular proteins are compact and water-soluble, facilitating transport throughout the body.

Alpha-Keratin: Structure and Function

  • Fibrous protein found in hair, nails, and skin.

  • Composed of two alpha-keratin chains forming a superhelix.

  • Provides strength and toughness to hair and nails.

Collagen: Structure, Function, and Vitamin C

  • Found in connective tissues such as bones, tendons, and blood vessels.

  • Formed from three helix structures that wrap around each other like a French braid.

  • Vitamin C stabilizes the structure.

  • Scurvy:

    • Caused by vitamin C deficiency.

    • Leads to breakdown of blood vessels, causing bleeding (e.g., gum bleeding).

    • Rare in developed countries due to vitamin C availability.

Hemoglobin and Myoglobin: Conjugated Globular Proteins

  • Conjugated proteins: contain protein and non-protein components (heme).

  • Heme molecule:

    • Contains Fe^{2+} (iron(II) cation), which binds oxygen.

    • Gives blood its red color.

  • Myoglobin:

    • Tertiary structure

    • Stores oxygen in cardiac and muscle cells.

    • Composed of a single polypeptide chain and a single heme molecule.

  • Hemoglobin:

    • Quaternary protein with four tertiary subunits (two alpha and two beta).

    • Each subunit contains a heme molecule, allowing it to transport four oxygen molecules.

    • Delivers oxygen throughout the body.

Heme and Oxygen Binding

  • Heme is chelated, holding iron in the center.

  • Iron (Fe2+) binds a single oxygen molecule (O_2).

  • Myoglobin releases oxygen when muscles are depleted, causing the burning sensation during workouts.

  • Red blood cells (erythrocytes) contain millions of hemoglobin molecules.

Insulin: A Globular Protein Hormone

  • Synthesized in the pancreas (islets of Langerhans) and released into the blood.

  • Regulates blood glucose levels.

  • Globular protein made of two polypeptide chains (A and B) held together by disulfide bonds.

  • Water solubility is essential to prevent precipitation and clot formation in the blood.

  • Insulin Production:

    • Transcription: DNA to mRNA.

    • Translation: mRNA to protein.

    • Preproinsulin: precursor molecule.

    • Proinsulin: converted to insulin and C-peptide in the Golgi apparatus.

    • Insulin is secreted into the bloodstream and binds to cells, facilitating glucose uptake.

Enzymes: Biological Catalysts

  • Catalysts speed up reaction rates without being changed themselves.

  • Enzymes are proteins that act as biological catalysts.

  • Identification: Enzymes often have names ending in "-ase".

Classification of Enzymes

  • Oxidoreductases

  • Transferases

  • Hydrolases

  • Isomerases

  • Lyases

  • Ligases

Enzyme Functions
  • Oxidases: oxidize molecules.

  • Dehydrogenases: remove hydrogen.

  • Transaminases: move amino groups.

  • Kinases: move phosphate groups (important in ATP production).

  • Lipases: hydrolyze lipids.

  • Nucleases: hydrolyze RNA and nucleic acids.

  • Proteases: degrade proteins by breaking peptide bonds.

Mechanisms of Enzyme Action

  • Enzymes favor reactions in one direction but can go back and forth.

  • Active Site: unique region on the enzyme where the substrate binds.

  • Enzyme-Substrate Complex: formed when enzyme and substrate are bound.

  • The enzyme remains unchanged after the reaction, while the substrate is converted to products.

  • Enzymes increase reaction rates by bringing reactants into close proximity.

Enzyme Models

  • Lock and Key Model: rigid active site with high specificity.

  • Induced Fit Model: flexible active site that changes shape to accommodate the substrate.

Factors Affecting Enzyme Activity

  • Temperature and pH: can alter enzyme function by affecting the bonds that hold the protein together.

  • Optimal temperature and pH ranges exist for maximum enzyme activity.

  • High temperatures can break apart proteins, causing them to lose function.

  • Changes in pH can also affect enzyme function.

Allosteric Control: Turning Enzymes On and Off

  • Regulators: molecules that bind to enzymes and can either turn them on or off.

  • Negative Allosteric Control:

    • A regulator binds to a site other than the active site, causing a conformational change.

    • The active site changes shape, preventing the substrate from binding, and turning the enzyme off.

  • Positive Allosteric Control:

    • A regulator binds to a site other than the active site, causing a conformational change.

    • The active site opens up, allowing the substrate to bind, and turning the enzyme on.

Enzyme Inhibitors: Competitive and Noncompetitive

  • Bind to enzymes and inhibit their activity.

    • Irreversible inhibitors: permanently destroy enzymatic activity.

    • Reversible inhibitors: temporarily turn off enzyme activity.

  • Competitive Inhibition:

    • Inhibitor competes with the substrate for the active site. The inhibitor binds to the active site first, preventing the substrate from binding.

  • Noncompetitive Inhibition:

    • Inhibitor binds to a site other than the active site, inducing a conformational change. The active site changes shape, preventing the substrate from binding.

Zymogens: Inactive Enzyme Precursors

  • Proenzymes: inactive enzymes that are activated when needed.

  • Enzymes ending in "-gen" are zymogens.

  • Example: Trypsinogen is an inactive form of trypsin.

  • Trypsin: An enzyme that breaks down proteins. It's found in the stomach and only activated when protein is present, to not damage the cells that have proteins.

    • Trypsinogen is converted to trypsin when protein is present.

Enzymes in Diagnostics

  • Enzymes can leak into the circulatory system, lymphatic system, or interstitial tissue when cells are damaged or die.

  • Measuring enzyme levels can indicate potential injury within the body.

  • Examples:

    • Creatine Phosphokinase: Elevated levels in the blood can signal a heart attack. It is normally not present within the circulatory system.

    • Acid Phosphatase: Can be a sign of prostate cancer.

    • Amylase and Lipase: Elevated levels in the blood can signal pancreatitis.

Enzymes as Drug Targets: ACE Inhibitors

  • Angiotensin-Converting Enzyme (ACE): increases blood pressure.

  • ACE Inhibitors: block the conversion of angiotensin I to angiotensin II, lowering blood pressure.

  • Renin-Angiotensin System:

    • Renin is released from the kidneys in response to low blood pressure or fluid volume.

    • Renin acts on angiotensinogen (released from the liver) to convert it to angiotensin I.

    • ACE (released from the lungs) converts angiotensin I to angiotensin II.

    • Angiotensin II stimulates aldosterone release from the adrenal gland.

    • Aldosterone increases water and salt retention in the kidneys, raising blood pressure.

    • Angiotensin II also causes vasoconstriction, increasing blood pressure.

  • ACE inhibitors prevent the conversion of angiotensin I to angiotensin II, blocking vasoconstriction and water retention, and thereby lowering blood pressure.

Amino Acids, Peptides, and Polypeptides
  • Anything over 40 amino acids is considered a protein.

  • Peptide bond: the bond between amino acids.

  • N terminus: corresponds to the 5' end of DNA and RNA.

  • C terminus: corresponds to the 3' end of DNA and RNA.

Enkephalins: Pentapeptides as Painkillers
  • Enkephalins are pentapeptides, meaning they consist of five amino acids.

  • Function: they signal to the brain and act as painkillers.

  • Mechanism: they bind to pain receptors, preventing stimuli transmission from nerve to nerve.

  • Runner's High: Enkephalins bind to pain receptors in the brain, reducing pain and fatigue and inducing euphoria after long runs.

Peptide Hormones: Oxytocin and Vasopressin
  • Oxytocin

    • Nine amino acid peptide (nonapeptide).

    • Produced by the posterior pituitary gland.

    • Functions:

    • Stimulates uterine contractions (used to induce labor).

    • Helps shrink the uterus back to normal size post-birth.

    • Signals to the breasts to contract, facilitating lactation.

  • Vasopressin

    • Antidiuretic hormone; nine amino acids in length.

    • Produced by the posterior pituitary gland.

    • Function:

    • Signals to the kidneys to retain fluid, reducing urine output and preventing dehydration.

Proteins: Polypeptides with Secondary Structures
  • Proteins are polypeptides greater than 40 amino acids in length that adopt secondary structures.

  • Two main types:

    • Fibrous proteins

    • Globular proteins

Fibrous Proteins
  • Long, linear proteins that wrap around each other (like a French braid).

  • Water insoluble; essential for structural components.

  • Examples:

    • Keratin

    • Alpha-keratin

    • Collagen

Globular Proteins
  • Compact, tangled structures.

  • Water soluble, allowing them to move throughout the body.

  • Examples:

    • Hemoglobin

    • Myoglobin

Protein Shape and Function
  • Every protein has a unique three-dimensional shape that dictates its function.

  • Fibrous proteins are long and water-insoluble.

  • Globular proteins are compact and water-soluble, facilitating transport throughout the body.

Alpha-Keratin: Structure and Function
  • Fibrous protein found in hair, nails, and skin.

  • Composed of two alpha-keratin chains forming a superhelix.

  • Provides strength and toughness to hair and nails.

Collagen: Structure, Function, and Vitamin C
  • Found in connective tissues such as bones, tendons, and blood vessels.

  • Formed from three helix structures that wrap around each other like a French braid.

  • Vitamin C stabilizes the structure.

  • Scurvy:

    • Caused by vitamin C deficiency.

    • Leads to breakdown of blood vessels, causing bleeding (e.g., gum bleeding).

    • Rare in developed countries due to vitamin C availability.

Hemoglobin and Myoglobin: Conjugated Globular Proteins
  • Conjugated proteins: contain protein and non-protein components (heme).

  • Heme molecule:

    • Contains Fe^{2+} (iron(II) cation), which binds oxygen.

    • Gives blood its red color.

  • Myoglobin:

    • Tertiary structure

    • Stores oxygen in cardiac and muscle cells.

    • Composed of a single polypeptide chain and a single heme molecule.

  • Hemoglobin:

    • Quaternary protein with four tertiary subunits (two alpha and two beta).

    • Each subunit contains a heme molecule, allowing it to transport four oxygen molecules.

    • Delivers oxygen throughout the body.

Heme and Oxygen Binding
  • Heme is chelated, holding iron in the center.

  • Iron (Fe^{2+}) binds a single oxygen molecule (O_2).

  • Myoglobin releases oxygen when muscles are depleted, causing the burning sensation during workouts.

  • Red blood cells (erythrocytes) contain millions of hemoglobin molecules.

Insulin: A Globular Protein Hormone
  • Synthesized in the pancreas (islets of Langerhans) and released into the blood.

  • Regulates blood glucose levels.

  • Globular protein made of two polypeptide chains (A and B) held together by disulfide bonds.

  • Water solubility is essential to prevent precipitation and clot formation in the blood.

  • Insulin Production:

    • Transcription: DNA to mRNA.

    • Translation: mRNA to protein.

    • Preproinsulin: precursor molecule.

    • Proinsulin: converted to insulin and C-peptide in the Golgi apparatus.

    • Insulin is secreted into the bloodstream and binds to cells, facilitating glucose uptake.

Enzymes: Biological Catalysts
  • Catalysts speed up reaction rates without being changed themselves.

  • Enzymes are proteins that act as biological catalysts.

  • Identification: Enzymes often have names ending in "-ase".

Classification of Enzymes
  • Oxidoreductases

  • Transferases

  • Hydrolases

  • Isomerases

  • Lyases

  • Ligases

Enzyme Functions

  • Oxidases: oxidize molecules.

  • Dehydrogenases: remove hydrogen.

  • Transaminases: move amino groups.

  • Kinases: move phosphate groups (important in ATP production).

  • Lipases: hydrolyze lipids.

  • Nucleases: hydrolyze RNA and nucleic acids.

  • Proteases: degrade proteins by breaking peptide bonds.

Mechanisms of Enzyme Action
  • Enzymes favor reactions in one direction but can go back and forth.

  • Active Site: unique region on the enzyme where the substrate binds.

  • Enzyme-Substrate Complex: formed when enzyme and substrate are bound.

  • The enzyme remains unchanged after the reaction, while the substrate is converted to products.

  • Enzymes increase reaction rates by bringing reactants into close proximity.

Enzyme Models
  • Lock and Key Model: rigid active site with high specificity.

  • Induced Fit Model: flexible active site that changes shape to accommodate the substrate.

Factors Affecting Enzyme Activity
  • Temperature and pH: can alter enzyme function by affecting the bonds that hold the protein together.

  • Optimal temperature and pH ranges exist for maximum enzyme activity.

  • High temperatures can break apart proteins, causing them to lose function.

  • Changes in pH can also affect enzyme function.

Allosteric Control: Turning Enzymes On and Off
  • Regulators: molecules that bind to enzymes and can either turn them on or off.

  • Negative Allosteric Control:

    • A regulator binds to a site other than the active site, causing a conformational change.

    • The active site changes shape, preventing the substrate from binding, and turning the enzyme off.

  • Positive Allosteric Control:

    • A regulator binds to a site other than the active site, causing a conformational change.

    • The active site opens up, allowing the substrate to bind, and turning the enzyme on.

Enzyme Inhibitors: Competitive and Noncompetitive
  • Bind to enzymes and inhibit their activity.

  • Irreversible inhibitors: permanently destroy enzymatic activity.

  • Reversible inhibitors: temporarily turn off enzyme activity.

  • Competitive Inhibition:

    • Inhibitor competes with the substrate for the active site. The inhibitor binds to the active site first, preventing the substrate from binding.

  • Noncompetitive Inhibition:

    • Inhibitor binds to a site other than the active site, inducing a conformational change. The active site changes shape, preventing the substrate from binding.

Zymogens: Inactive Enzyme Precursors
  • Proenzymes: inactive enzymes that are activated when needed.

  • Enzymes ending in "-gen" are zymogens.

  • Example: Trypsinogen is an inactive form of trypsin.

    • Trypsin: An enzyme that breaks down proteins. It's found in the stomach and only activated when protein is present, to not damage the cells that have proteins.

    • Trypsinogen is converted to trypsin when protein is present.

Enzymes in Diagnostics
  • Enzymes can leak into the circulatory system, lymphatic system, or interstitial tissue when cells are damaged or die.

  • Measuring enzyme levels can indicate potential injury within the body.

  • Examples:

    • Creatine Phosphokinase: Elevated levels in the blood can signal a heart attack. It is normally not present within the circulatory system.

    • Acid Phosphatase: Can be a sign of prostate cancer.

    • Amylase and Lipase: Elevated levels in the blood can signal pancreatitis.

Enzymes as Drug Targets: ACE Inhibitors
  • Angiotensin-Converting Enzyme (ACE): increases blood pressure.

  • ACE Inhibitors: block the conversion of angiotensin I to angiotensin II, lowering blood pressure.

  • Renin-Angiotensin System:

    • Renin is released from the kidneys in response to low blood pressure or