Chapter 5
• Protein Classification
o Shape
§ Globular
• Spherical
• Functional for transport
• Soluble in water
• Irregular amino acid sequence
• More sensitive to heat and pH
• Ex: Catalase, haemoglobin, insulin, myoblobin, immunoglobulin
• Antibodies
§ Fibrous
• Linear
• Structural
o 𝛼 Helix
§ Tough and insoluble
§ Ex: 𝛼-Keratin of hair, feathers, nails
§ 𝜶-Keratin
• Right handed alpha helices
• Intra-chain H bonds within same chain
• Disulfide bonds
• Repeats of 7 (heptad) amino acids
o 𝛽 conformation
§ Soft and flexible
§ Ex: silk fibroin
• Gly and Ala allow close sheet packing
• Every 2nd amino acid is Gly
• Anti-parallel beta sheets
• Interchain H bonds between chains
o Collagen triple helix
§ Strong and not stretchy
§ Ex: Collagen of tendons, bone matrix
§ Collagen
• Part of connective tissue matrix
• Helices (not alpha)
• Gly, Pro, and hydroxyproline
o Hydroxyproline from vitamin C
o Less vitamin C means you look older
• Every 3rd amino acid is Gly
• Interchain H bonds between chains
• Insoluble in water
• Repetitive amino acid sequence
• Less sensitive to heat and pH
, • Ex: Collagen, myosin, fibrin, actin, keratin, elastin
Fibrous Structure Modified amino H Bonds Function
Protein acid
Keratin RH 𝛼 helix Every 7 repeats Intrachain Hair, feathers, nails
Silk fibroin AP 𝛽 sheet Every 2nd = Gly Interchain Silk
rd
Collagen Helix Every 3 = Gly Interchain Connective tissue/bones
o Composition
§ Simple
• Contain only amino acids
§ Conjugated
• Contain protein and non-protein component
• Ex: glycoprotein and lipoprotein
• Oxygen Binding
o Affected by
§ Availability of oxygen
§ Binding of first oxygen molecule
§ The Bohr Effect (pH)
• More acidic = less oxygen affinity
o H+ ions decrease oxygen affinity
• Lowered by
o Bicarbonate buffering system
o Lactic acid production
o Metabolizing
• H ions protonate His, which forms a salt bridge with Asp to
+
release oxygen
§ Presence of CO2
• Produced by metabolism
o Exercise
• 15-20% exported in carbamate on the amino terminal residues
o Formation of carbamate releases a proton
o Forms additional salt bridges
• Inhibits O2 binding
o Competes with oxygen for the same hemoglobin
o Binds 250x more tightly to heme of hemoglobin than O2
does
o Permanent CO binding
§ Inhibition by 2,3 BPG
• Negative heterotropic regulator of Hb function
• Present at mM concentrations in erythrocytes
o Produced from an intermediate in glycolysis
• Small negatively charged molecule
o Binds to positively charged Histidine of hemoglobin
, • Stabilizes T state
o Hemoglobin
§ Similar tertiary structure to myoglobin
§ Same heme group as myoglobin to bind oxygen
• Prosthetic group
• Complex of porphyrin IX and ferrous iron (Fe2+)
§ Oxygen transport
• Lower oxygen affinity than myoglobin
• Oxygen from lungs to tissues
§ Tetramer
• Four subunits
• Can bind to four oxygens
• Cooperative binding, where when one oxygen has bound, it’s
easier for more to bind
§ Found in red blood cells
§ T and R states
• T state has histidine pointing down
o More stable
o Lower oxygen affinity
o The first oxygen binding triggers conformational change
• T à R breaks ion pairs between 𝛼1- 𝛽2 interact
o Only R state can bind to oxygen
§ Has histidine in the middle for Fe2+ to bind
• 𝛽 position
§ Fewer interactions
§ Higher oxygen affinity
o T state stabilized at low pH
§ Has protonated histidine (His+) which would form
ionic interactions with aspartic acid (Asp-)
• Thus cannot bind to oxygen
• The ionic bonds stabilize T state
• Bohr Effect
§ Exercise contributes to T state
• Lactic acid buildup
• Gives off protons to stabilize T state
§ 2,3 BPG stabilizes T state
• Binds to central Histidine
• Forms a salt bridge
§ Fetal Hb
• No His 143
o Instead, Ser 143 in 𝛾 subunit
• 2 𝛼, 2 𝛾 subunits
• Higher O2 affinity
, • Does not bind to 2,3 BPG
o Myoglobin
§ Similar tertiary structure to hemoglobin
§ Same heme group as hemoglobin to bind oxygen
• Prosthetic group
• Complex of porphyrin IX and ferrous iron (Fe2+)
§ Oxygen transport
• High oxygen affinity
§ Monomer
• One subunit
• Can only bind to one oxygen
§ Found in skeletal/cardiac muscles
Hemoglobin Myoglobin
Similar tertiary structure Similar tertiary structure
Same heme group Same heme group
Lower O2 affinity Higher O2 affinity
Red blood cells Skeletal/cardiac muscles
4 subunits can bind 4 oxygens 1 subunit can bind 1 oxygen
T/R states No T/R states
o
• Mutations in Proteins
o Substitution
§ One amino acid changed out for another
§ Sickle-Cell Anemia
• Hb Glu 6 is substituted with Val 6 on the surface of 𝛽 subunits
• Hydrophobic Val binds to hydrophobic pockets in other 𝛽 subunits
• Only heterozygous people can survive
• Makes one resistant to malaria
• Sickle-cells are rigid and cannot pass through capillaries as easily
o Targeted by immune system
o Less efficient at carrying oxygen
Chapter 6
• History of enzymes
o Fermentation
o Pancreatic enzymes
§ Human pancreas made fluids that process carbohydrates and fats
• Whereas saliva only breaks down carbohydrates
§ Malfunctioning of pancreas = malabsorption of fats
• Definition
o Biological catalyst
o Normally a protein, rarely RNA
o Speeds up the rate of a biological reaction
• Protein Classification
o Shape
§ Globular
• Spherical
• Functional for transport
• Soluble in water
• Irregular amino acid sequence
• More sensitive to heat and pH
• Ex: Catalase, haemoglobin, insulin, myoblobin, immunoglobulin
• Antibodies
§ Fibrous
• Linear
• Structural
o 𝛼 Helix
§ Tough and insoluble
§ Ex: 𝛼-Keratin of hair, feathers, nails
§ 𝜶-Keratin
• Right handed alpha helices
• Intra-chain H bonds within same chain
• Disulfide bonds
• Repeats of 7 (heptad) amino acids
o 𝛽 conformation
§ Soft and flexible
§ Ex: silk fibroin
• Gly and Ala allow close sheet packing
• Every 2nd amino acid is Gly
• Anti-parallel beta sheets
• Interchain H bonds between chains
o Collagen triple helix
§ Strong and not stretchy
§ Ex: Collagen of tendons, bone matrix
§ Collagen
• Part of connective tissue matrix
• Helices (not alpha)
• Gly, Pro, and hydroxyproline
o Hydroxyproline from vitamin C
o Less vitamin C means you look older
• Every 3rd amino acid is Gly
• Interchain H bonds between chains
• Insoluble in water
• Repetitive amino acid sequence
• Less sensitive to heat and pH
, • Ex: Collagen, myosin, fibrin, actin, keratin, elastin
Fibrous Structure Modified amino H Bonds Function
Protein acid
Keratin RH 𝛼 helix Every 7 repeats Intrachain Hair, feathers, nails
Silk fibroin AP 𝛽 sheet Every 2nd = Gly Interchain Silk
rd
Collagen Helix Every 3 = Gly Interchain Connective tissue/bones
o Composition
§ Simple
• Contain only amino acids
§ Conjugated
• Contain protein and non-protein component
• Ex: glycoprotein and lipoprotein
• Oxygen Binding
o Affected by
§ Availability of oxygen
§ Binding of first oxygen molecule
§ The Bohr Effect (pH)
• More acidic = less oxygen affinity
o H+ ions decrease oxygen affinity
• Lowered by
o Bicarbonate buffering system
o Lactic acid production
o Metabolizing
• H ions protonate His, which forms a salt bridge with Asp to
+
release oxygen
§ Presence of CO2
• Produced by metabolism
o Exercise
• 15-20% exported in carbamate on the amino terminal residues
o Formation of carbamate releases a proton
o Forms additional salt bridges
• Inhibits O2 binding
o Competes with oxygen for the same hemoglobin
o Binds 250x more tightly to heme of hemoglobin than O2
does
o Permanent CO binding
§ Inhibition by 2,3 BPG
• Negative heterotropic regulator of Hb function
• Present at mM concentrations in erythrocytes
o Produced from an intermediate in glycolysis
• Small negatively charged molecule
o Binds to positively charged Histidine of hemoglobin
, • Stabilizes T state
o Hemoglobin
§ Similar tertiary structure to myoglobin
§ Same heme group as myoglobin to bind oxygen
• Prosthetic group
• Complex of porphyrin IX and ferrous iron (Fe2+)
§ Oxygen transport
• Lower oxygen affinity than myoglobin
• Oxygen from lungs to tissues
§ Tetramer
• Four subunits
• Can bind to four oxygens
• Cooperative binding, where when one oxygen has bound, it’s
easier for more to bind
§ Found in red blood cells
§ T and R states
• T state has histidine pointing down
o More stable
o Lower oxygen affinity
o The first oxygen binding triggers conformational change
• T à R breaks ion pairs between 𝛼1- 𝛽2 interact
o Only R state can bind to oxygen
§ Has histidine in the middle for Fe2+ to bind
• 𝛽 position
§ Fewer interactions
§ Higher oxygen affinity
o T state stabilized at low pH
§ Has protonated histidine (His+) which would form
ionic interactions with aspartic acid (Asp-)
• Thus cannot bind to oxygen
• The ionic bonds stabilize T state
• Bohr Effect
§ Exercise contributes to T state
• Lactic acid buildup
• Gives off protons to stabilize T state
§ 2,3 BPG stabilizes T state
• Binds to central Histidine
• Forms a salt bridge
§ Fetal Hb
• No His 143
o Instead, Ser 143 in 𝛾 subunit
• 2 𝛼, 2 𝛾 subunits
• Higher O2 affinity
, • Does not bind to 2,3 BPG
o Myoglobin
§ Similar tertiary structure to hemoglobin
§ Same heme group as hemoglobin to bind oxygen
• Prosthetic group
• Complex of porphyrin IX and ferrous iron (Fe2+)
§ Oxygen transport
• High oxygen affinity
§ Monomer
• One subunit
• Can only bind to one oxygen
§ Found in skeletal/cardiac muscles
Hemoglobin Myoglobin
Similar tertiary structure Similar tertiary structure
Same heme group Same heme group
Lower O2 affinity Higher O2 affinity
Red blood cells Skeletal/cardiac muscles
4 subunits can bind 4 oxygens 1 subunit can bind 1 oxygen
T/R states No T/R states
o
• Mutations in Proteins
o Substitution
§ One amino acid changed out for another
§ Sickle-Cell Anemia
• Hb Glu 6 is substituted with Val 6 on the surface of 𝛽 subunits
• Hydrophobic Val binds to hydrophobic pockets in other 𝛽 subunits
• Only heterozygous people can survive
• Makes one resistant to malaria
• Sickle-cells are rigid and cannot pass through capillaries as easily
o Targeted by immune system
o Less efficient at carrying oxygen
Chapter 6
• History of enzymes
o Fermentation
o Pancreatic enzymes
§ Human pancreas made fluids that process carbohydrates and fats
• Whereas saliva only breaks down carbohydrates
§ Malfunctioning of pancreas = malabsorption of fats
• Definition
o Biological catalyst
o Normally a protein, rarely RNA
o Speeds up the rate of a biological reaction
