Cell bio enzymes 1 & 2 Flashcards
IMP IMP IMP!!!!!
SALIVARY GLANDS
enzymes:
- ? (Ptyalin): amylose (polysaccharide) ->
- ? lipase: Lipids (TAG, cholesterol) -> ?
STOMACH
enzymes:
1. ? (protease): proteins ->
2. ? lipase: Lipids (TAG, cholesterol) -> ?
PANCREAS
enzymes:
1. ?: Polysaccharides > disaccharides
2. Trypsin (protease): Proteins -> ?
3. ? (protease): Proteins -> peptides
4. ?: Lipids -> DAG, MAG, FFA, glycerol
SMALL INTESTINE BRUSH BORDER
1. peptidases: Polypeptides -> ?
2. nucleotidases: ? -> nucleotides, ribose
3. lactase: Disaccharides -> ?
4. maltase: ? -> monosaccharides
5. sucrase: ? -> monosaccharides
ENSURE TO TEST YOURSELF ON THIS!
DR. CAMARGO SAID “U MUST KNOW ALL OF IT!!”
IMP IMP IMP!!!!!
SALIVARY GLANDS
enzymes:
- alpha-amylase (Ptyalin): amylose (polysaccharide) ->
- lingual lipase: Lipids (TAG, cholesterol) -> ?
STOMACH
enzymes:
1. pepsin (protease): proteins -> peptides
2. gastric lipase: Lipids (TAG, cholesterol) -> DAG, MAG, FFA, glycerol
PANCREAS
enzymes:
1. pancreatic amylase: Polysaccharides > disaccharides
2. Trypsin (protease): Proteins -> peptides
3. chymotrypsin (protease): Proteins -> peptides
4. acid : Lipids -> DAG, MAG, FFA, glycerol
SMALL INTESTINE BRUSH BORDER
1. peptidases: Polypeptides -> amino acids
2. nucleotidases: DNA, RNA -> nucleotides, ribose
3. lactase: Disaccharides -> monosaccharides
4. maltase: Disaccharides -> monosaccharides
5. sucrase: Disaccharides -> monosaccharides
Most all diseases in animals are manifestations of abnormalities in:
- ?
- ?
- ?
Most all diseases in animals are manifestations of abnormalities in:
- biomolecules
- chemical rxns
- biochemical pathways
ENZYMES
Enzymes are ? that act as ? by accelerating chemical reactions.
The molecules upon which enzymes may act are called ?, and the enzyme converts the substrates into different molecules known as ?.
They have a ? for their substrates, and they accelerate chemical reactions tremendously, without being ? or used up during the process (?).
Generally, a small amount of enzyme will influence a ? of reactive substrate.
Act as ? for virtually all chemical reactions in biological systems, playing fundamental roles in metabolic events, ? and cell regulation.
ENZYMES
Enzymes are proteins that act as biological catalysts by accelerating chemical reactions.
The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products.
They have a high degree for their substrates, and they accelerate chemical reactions tremendously, without being changed or used up during the process (reversible binding).
Generally, a small amount of enzyme will influence a large amount of reactive substrate.
Act as mediators for virtually all chemical reactions in biological systems, playing fundamental roles in metabolic events, signal transduction and cell regulation.
in the image: E = enzyme; S = substrate ES=enzyme substrate complex; P = product
ENZYMES
The binding is very ?, small changes in the shape of the ligand/substrate (key) can cause major change in protein (lock) behavior.
Complementary shape: ? function, plays a major role in ?
[story: enzyme is the lock and substrate is the key (thus substrate seeks help from the Goddess enzyme and goddess enzyme fulfills substrate’s wish i.e., to create a product)]
?: the ability of a protein to change shape, resulting in a change in binding affinity at a different binding site.
Allosteric enzymes: have the ? site, as well as an ? site (allosteric site) *
(From the Greek ‘allo’, which means ‘other’.)
“shape influences binding, and in turn, binding can influence shape”
ENZYMES
The binding is very specific, small changes in the shape of the ligand/substrate (key) can cause major change in protein (lock) behavior.
Complementary shape: recognition function, plays a major role in information transfer
ALLOSTERY: the ability of a protein to change shape, resulting in a change in binding affinity at a different binding site.
Allosteric enzymes: have the binding site, as well as an additional site (allosteric site) *
(From the Greek ‘allo’, which means ‘other’.)
“shape influences binding, and in turn, binding can influence shape”
LIFE DEPENDS ON A COMPLEX NETWORK OF CHEMICAL REACTIONS
? metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to ? life.
Binding sites of enzymes are usually very specific for a particular ?/? and the binding is ?.
[some enzymes have diff. active sites and each active site will have their own specific binding site to which appropriate substrates will bind to]
almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life.
The binding sites of enzymes are usually very specific for a particular ligand/substrate and the binding is reversible.
INDUSTRIAL FIELDS ALSO BENEFITS FROM ENZYMES
* ? production (biodiesel, alcohol from sugar cane)
* ? (animal feed additives, fertilizers…)
* Fermentations: transformation of raw materials such as ? etc. in industrial mixtures such as liquors, brewing
* ?: transformation of defined precursors to a desired target product
o Environmentally friendly processes to treat ? (some fungi being used to degrade ?)
* Pharmaceutical industry: synthesis & modification of ?
* ? of disease: increased or decreased concentrations of enzyme activity in the target system (liver, kidney, muscle)
* Treatment of disease: i.e. use of ? to dissolve blood clots
sidenotes:
in brazil most cars move from alcohol made from sugar cane
INDUSTRIAL FIELDS ALSO BENEFITS FROM ENZYMES
* biofuel production (biodiesel, alcohol from sugar cane)
* agricultural (animal feed additives, fertilizers…)
* Fermentations: the transformation of raw materials such as sugar, starch etc. in industrial mixtures such as liquors, brewing
* biotransformation: transformation of defined precursors to a desired target product
o Environmentally friendly processes to treat waste (some fungi being used to degrade waste)
* Pharmaceutical industry: synthesis & modification of medicines, antibiotics
* diagnosis of disease: increased or decreased concentrations of enzyme activity in the target system (liver, kidney, muscle)
* Treatment of disease: i.e. use of streptokinase to dissolve blood clots
INDUSTRIAL ENZYMES AND THEIR USES
*IMP!
1. protease: degradation of ? -> detergents
2. cellulase: degradation of ? -> detergents
3. lipase: degradation of ? -> detergents
IMP. TO KNOW THIS (when working in vaccines, sanitizing things so using detergents thus need to know what each type of detergent so it doesn’t clash w each other)*
HOW ENZYMES WORK?
* Chemical reactions have an ? separating the reactants and the products.
* Energy is needed to get them started = known as ?
* Enzymes greatly ? the activation energy ? that block chemical reactions.
NDUSTRIAL ENZYMES AND THEIR USES
- protease: degradation of proteins -> detergents
- cellulase: degradation of cellulose -> detergents
- lipase: degradation of lipids -> detergents
IMP. TO KNOW THIS (when working in vaccines, sanitizing things so using detergents thus need to know what each type of detergent so it doesn’t clash w each other)
HOW ENZYMES WORK?
* Chemical reactions have an energy barrier separating the reactants and the products.
* Energy is needed to get them started = known as activation energy
* Enzymes greatly reduce the activation energy barrier that block chemical reactions.
HOW ENZYMES WORK?
Enzymes ? molecules through a specific ? pathway
* allowing a reaction to proceed ? by providing an ? reaction pathway in the cell which has a lower activation energy.
Enzymes show a ? and usually catalyze ? specific reaction, or a set of ? reactions; directing a particular reaction pathway.
THE TRANSITION STATE
* The ? acts as a molecular template that binds the substrate and initiates its conversion to the ?
- The ? state is the form the substrate must take before it becomes ?.
- It is the ? energy point of the reaction.
? the transition state (T) an enzyme can greatly increase the ? of the reactive intermediate that can be converted to product thus accelerating the reaction.
HOW ENZYMES WORK?
Enzymes direct substrate molecules through a specific reaction pathway
* allowing a reaction to proceed rapidly by providing an alternate reaction pathway in the cell which has a lower activation energy.
Enzymes show a high selectivity and usually catalyze only one specific reaction, or a set of closely related reactions; directing a particular reaction pathway.
THE TRANSITION STATE
* The active site acts as a molecular template that binds the substrate and initiates its conversion to the transition state
- The transition state is the form the substrate must take before it becomes product
- It is the highest energy point of the reaction.
- stabilizing the transition state (T*) an enzyme can greatly increase the concentration of the reactive intermediate that can be converted to product thus accelerating the reaction.
NOMENCLATURE
Recommended name: short name, most used, has the suffix ‘-ase’ attached to
[enzyme named a/c to substrates, description of rxn and full names for scientific papers]
- the “ ? “ of the reaction: i.e., “Gluco”kinase (found mostly in liver and pancreas, phosphorylation of glucose)
- the “ ? “ of the reaction performed: i.e., Lactate “dehydrogen”ase
” ? “: more complete, complex; is used when an enzyme must be identified without ? (used in scientific papers)
The suffix -ase is attached to a more complete description of the chemical reaction catalyzed, including the “names of all substrates”: e.g. LDH (lactate dehydrogenase): Lactate, NAD+oxidoreductase
The systematic names are unambiguous and informative, but often too big for general use
NOMENCLATURE
Recommended name: short name, most used, has the suffix ‘-ase’ attached to
[enzyme named a/c to substrates, description of rxn and full names for scientific papers]
- the “substrate” of the reaction: i.e., “Gluco”kinase (found mostly in liver and pancreas, phosphorylation of glucose)
- the “description” of the reaction performed: i.e., Lactate “dehydrogen”ase
“systemic name”: more complete, complex; is used when an enzyme must be identified without ambiguity (used in scientific papers)
The suffix -ase is attached to a more complete description of the chemical reaction catalyzed, including the “names of all substrates”: e.g. LDH (lactate dehydrogenase): Lactate, NAD+oxidoreductase
The systematic names are unambiguous and informative, but often too big for general use
*imp!
Pepsin
substrate: ?
products: short polypeptides
Rennin
substrate: soluble ? (milk protein)
product: ? (curdled milk)*
MAJOR CLASSES OF ENZYME
- Oxidoreductases: catalyze reactions in which one molecule is ? while the other is ?, transfer of electrons (e-) and ?
e.g. of enzymes: oxidases, ?, dehydrogenases, ?
(lactate dehydrogenase (NAD+ -> NADH + H)) - Transferases: transfer carbon, ? or ? groups
e.g. methyltransferases, ?, kinases, ? (serine hydroxymethyl transferase: serine -> glycine and CH2) - Hydrolases: enzymes that catalyze a ? reaction (use water to break a chemical bond) *most ? are hydrolases as they (e.g. lipase) which need to reach the hydrophobic part of lipids need water around to break down the chemical bond
e.g. nucleases, ?, phosphatases (urease: urea -> carbon di oxide and ammonia) - Lyases: catalyze the cleavage of ? bonds
(catalyzes the breaking of various chemical bonds by means other than ? and ?, often forming a new double bond or a new ring structure)
e.g. decarboxylases, ?, synthases, ? (e.g. pyruvate decarboxylate: pyruvate -> acetaldehyde) - Isomerases: catalyze the ? of bonds within a ? molecule, transfer of groups within molecules to yield ?
e.g. mutases, ? (methylmalonyl CoA mutase: methylmalonyl CoA to succinyl CoA)
Ligases: Join two molecules in an ? process and
Catalyze formation of bonds between carbon and ?, ? and ? coupled to hydrolysis of ? (get energy mainly from ATP) phosphates (pyruvate carboxylase: pyruvate -> oxaloacetate)
*imp!
Pepsin
substrate: protein
products: short polypeptides
Rennin
substrate: soluble casein (milk protein)
product: insoluble casein (curdled milk)*
MAJOR CLASSES OF ENZYME
- Oxidoreductases: catalyze reactions in which one molecule is oxidized while the other is reduced, transfer of electrons (e-) and hydrogens (H+)
e.g. of enzymes: oxidases, reductases, dehydrogenases, ?
(lactate dehydrogenase (NAD+ -> NADH + H) here COOH looses an electron and NAD gains an electron in the product side) - Transferases: transfer carbon, ? or ? groups
e.g. methyltransferases, ?, kinases, ? (serine hydroxymethyl transferase: serine -> glycine and CH2) - Hydrolases: enzymes that catalyze a hydrolytic cleavage reaction (use water to break a chemical bond) *most digestive enzymes are hydrolases as they (e.g. lipase) which need to reach the hydrophobic part of lipids need water around to break down the chemical bond
e.g. nucleases, proteases, phosphatases (urease: urea -> carbon di oxide and ammonia) - Lyases: catalyze the cleavage of C-C, C-S and C-N bonds
(catalyzes the breaking of various chemical bonds by means other than hydrolysis and oxidation, often forming a new double bond or a new ring structure)
e.g. decarboxylases, aldolases, synthases, polymerases (e.g. pyruvate decarboxylate: pyruvate -> acetaldehyde) - Isomerases: catalyze the rearrangment of bonds within a single molecule, transfer of groups within molecules to yield isomeric forms
e.g. mutases, racemases (methylmalonyl CoA mutase: methylmalonyl CoA to succinyl CoA)
Ligases: Join two molecules in an energy-dependent process (usually from ATP) and
Catalyze formation of bonds between carbon and oxygen, sulfur and nitrogen coupled to hydrolysis of high energy phosphates (get energy mainly from ATP) phosphates (pyruvate carboxylase: pyruvate -> oxaloacetate)
note:
lyases = catalyze cleavage of C-C, C-S, C-N
ligases = join molecules between C-O, C-S, C-N
NOMENCLATURE
POTENTIALLY CONFUSING ENZYME NOMENCLATURE:
- Synthetase: ? ATP
- Synthase: ? ATP
- Phosphatase: ? phosphates
- Phosphorylase: ? phosphates (cleave bonds by ? - phosphorolysis)
- Dehydrogenase: catalyze ? reactions (i.e., transferring hydrogen to NAD+/NADPH+)
- Oxidase: ? is the acceptor of electrons or hydrogen, and oxygen atoms are not incorporated into ?
- Oxygenase: catalyze the incorporation of molecular O2 to a ?.
NOMENCLATURE
POTENTIALLY CONFUSING ENZYME NOMENCLATURE:
- Synthetase: ATP needed
- Synthase: no ATP needed
- Phosphatase: removes phosphates
- Phosphorylase: add phosphates (cleave bonds by orthophosphate - phosphorolysis)
- Dehydrogenase: catalyze oxidation/reduction reactions (i.e., transferring hydrogen to NAD+/NADPH+)
- Oxidase: oxygen is the acceptor of electrons or hydrogen, and oxygen atoms are not incorporated into substrate
- Oxygenase: catalyze the incorporation of molecular O2 to a substrate.
CLASSES OF ENZYMES
Polymerases: catalyze polymerization reactions such as the synthesis of ?
Proteases: break down proteins by ? bonds between ?
Kinases: Catalyze the addition of ? groups to molecules (protein kinases are very common in physiology)
?: Hydrolyze ATP (Na, K- ATPase)
Synthases: synthesize molecules in ? reactions by condensing two smaller molecules together with or w/o using ATP?
Phosphatase: catalyze the hydrolytic ? of a phosphate group from a molecule
PROPERTIES OF ENZYMES
- Active sites: enzymes contain a special
pocket called the ‘?’ which has a
high ?
AAs contain amino acid ? that
participate in substrate binding and catalysis
active sites are:
* “ ? ”
* Sensitive to ? changes
* ? by high heat
* Inhibited by ?
CLASSES OF ENZYMES
Polymerases: catalyze polymerization reactions such as the synthesis of dna and rna
Proteases: break down proteins by hydrolyzing bonds between AAs
Kinases: Catalyze the addition of phosphate groups to molecules (protein kinases are very common in physiology)
ATPase: Hydrolyze ATP (Na, K- ATPase)
Synthases: synthesize molecules in anabolic reactions by condensing two smaller molecules together w/o using ATP
Phosphatase: catalyze the hydrolytic removal of a phosphate group from a molecule
PROPERTIES OF ENZYMES
- Active sites: enzymes contain a special
pocket called the ‘active’ which has a
high specificity
AAs contain amino acid side chain that
participate in substrate binding and catalysis
active sites are:
* “ reusable ”
* Sensitive to pH changes
* denatured by high heat
* Inhibited by poison
PROPERTIES OF ENZYMES
Catalytic Efficiency: reactions catalyzed by enzymes are #? times faster than uncatalyzed reactions.
Specificity: enzymes interact with ALOT OR FEW substrates? and catalyze only one type of chemical reaction.
Presence of Cofactor and coenzymes:
- what does apoenzyme need for it to work?
- vitamin is analogous to ? in terms of function
*? and ? are often the metabolically active form of the vitamins.
PROPERTIES OF ENZYMES
Catalytic Efficiency: reactions catalyzed by enzymes are 103-108 times faster than uncatalyzed reactions.
Specificity: enzymes interact with one or v few substrates and catalyze only one type of chemical reaction.
Presence of Cofactor and coenzymes:
- what does apoenzyme need for it to work? = “cofactor” thus apoenzyme + cofactor = holoenzyme
- vitamin is analogous to cofactor in terms of function (enzymes in body need vitamins to produce e.g. holoenzyme)
*coenzymes and cosubstrates are often the metabolically active form of the vitamins.
PROPERTIES OF ENZYMES
Location in the cell: Many enzymes are in specific ? in the cell (?) and in specific ?
some reactions are isolated from others (avoiding ? for the substrate or enabling more favorable conditions, like ?)
Recall: protein sorting importance to maintain this ?.
e.g. cytosol: here glycolysis, PPP, FA synthesis;
mitochondria: TCA cycle, fatty acid oxidation, oxidation of pyruvate
nucleus: dna and rna synthesis
PROPERTIES OF ENZYMES
Location in the cell: Many enzymes are in specific organelles in the cell and in specific cells
some reactions are isolated from others (avoiding competition for the substrate or enabling more favorable conditions, like pH)
Recall: protein sorting is important to maintain compartmentalization.
e.g. cytosol: here glycolysis, PPP, FA synthesis;
mitochondria: TCA cycle, fatty acid oxidation, oxidation of pyruvate
nucleus: dna and rna synthesis
ENZYME KINETICS
The study of the ? that are catalyzed by ?.
Studying enzyme kinetics allows for the understanding of how each ? works.
o The enzyme’s ? mechanism
o The control of enzyme ?
o Its role in ?
o Possible inhibition by ?, agonists or antagonists
ENZYME KINETICS
The study of the chemical rxn that are catalyzed by enzymes
Studying enzyme kinetics allows for the understanding of how each enzyme works.
o The enzyme’s catalytic mechanism
o The control of enzyme activity
o Its role in metabolism
o Possible inhibition by drugs, agonists or antagonists
MICHAELIS-MENTEN KINECTS
The equation describes how ? varies with ? concentration -> single substrate enzyme kinetics!
An enzyme reversibly combines with its substrate to form an ? complex that yields a product P, releasing the free ?.
[in vitro = in glass (laboratory)
in vivo = in live animals]
Assumptions/conditions:
Relative concentration of enzyme and substrate
[S] > > [E] → % of total substrate bound by the enzyme at any one time is small
?: ES complex does not change with time. Rate [ES] formation = [ES] disassociation
? velocity (V0): reaction is measured as soon as enzyme and substrate are mixed.
Concentration of ? is very small. Rate of P -> ES can be ignored
Total enzyme concentration [E] does not change or changes over time?
Equation describes how reaction velocity varies with substrate concentration -> single substrate enzyme kinetics!
An enzyme reversibly combines with its substrate to form an ES complex that yields a product P, releasing the free enzyme.
Assumptions/conditions:
Relative concentration of enzyme and substrate
[S] > > [E] → % of total substrate bound by the enzyme at any one time is small
steady state: ES complex does not change with time. Rate [ES] formation = [ES] disassociation
initial velocity (V0): reaction is measured as soon as enzyme and substrate are mixed.
Concentration of P is very small. Rate of P -> ES can be ignored
Total enzyme concentration [E] does not change over time?
Enzyme 1 has a high affinity for its substrate because a ? concentration of ? is needed to ?-saturate the enzyme
-> this is represented in the small Km
Enzyme 2 shows a ? affinity to the substrate -> represented in the large Km
Relationship of initial velocity to enzyme concentration:
→ rate of the reaction is directly proportional to the ? concentration at all substrate concentrations. (if 1⁄2 [E] → 1⁄2 ? and ?)
(if more enzymes added then initial velocity and max velocity can be increased and if enzymes reduced then less enzymes to react w substrate so velocity also goes down)
Order of reaction:
First order [ ? ] < < Km the velocity of the reaction is nearly proportional to the ? concentration.
(“linear curve” thus adding substrates then can increase velocity but not the case for zero order)
Zero order [ ? ] > > Km the velocity of the reaction is ? and equal to ?
-> rate of reaction is ? of substrate concentration
(reaching a plateau after Km)
Enzyme 1 has a high affinity for its substrate because a low concentration of substrate is needed to half-saturate the enzyme
-> this is represented in the small Km
Enzyme 2 shows a low affinity to the substrate -> represented in the large Km
Relationship of initial velocity to enzyme concentration:
→ rate of the reaction is directly proportional to the enzyme concentration at all substrate concentrations. (if 1⁄2 [E] → 1⁄2 Vo and Vmax)
(if more enzymes added then initial velocity and max velocity can be increased and if enzymes reduced then less enzymes to react w substrate so velocity also goes down)
Order of reaction:
First order [S] < < Km the velocity of the reaction is nearly proportional to the substrate concentration.
(“linear curve” thus adding substrates then can increase velocity but not the case for zero order)
Zero order [S] > > Km the velocity of the reaction is constant and equal to Vmax
-> rate of reaction is independent of substrate concentration
(reaching a plateau after Km)
THE LINEWEAVER-BURK PLOT
When Vo is plotted against [S], it is not always possible to determine when Vmax is achieved because of the ?.
(saturation of enzyme with substrate is known as ? )
Mathematically, the reciprocal 1/v0
and 1/[S] will be plotted to obtain a
straight line
* Calculation of Km and Vmax → enzyme ?
* It can also help to determine the mechanism of action of enzyme ?
(so we know the exact number on x and y so no need to use complicated math formulas)
THE LINEWEAVER-BURK PLOT
When Vo is plotted against [S], it is not always possible to determine when Vmax is achieved because of the hydperbolic curve.
(saturation of enzyme with substrate is known as Vmax)
Mathematically, the reciprocal 1/v0
and 1/[S] will be plotted to obtain a
straight line
* Calculation of Km (x) and Vmax (y) → enzyme activity
* It can also help to determine the mechanism of action of enzyme inhibitors
(so we know the exact number on x and y so no need to use complicated math formulas)
- Effect on Vmax: inhibitor effect is ? by increasing [S]
High enough [S] → reaction velocity reaches the same Vmax observed in the absence of inhibitor - Effect on Km: competitive inhibitor ? for given substrate
competitive inhibitor reduces ? of E for S (competing!!) More substrate is needed to reach 1⁄2 Vmax - Effect on the Lineweaver-Burk plot
- 1/Vmax = changes or unchanged?
- 1/Km (think 1/Km = affinity) is ? in the presence of the competitive inhibitor
- Effect on Vmax: inhibitor effect is reversed by increasing [S]
High enough [S] → reaction velocity reaches the same Vmax observed in the absence of inhibitor - Effect on Km: competitive inhibitor increases Km for given substrate
competitive inhibitor reduces affinity of E for S (competing!!) More substrate is needed to reach 1⁄2 Vmax - Effect on the Lineweaver-Burk plot
- 1/Vmax = unchanged
- 1/Km (think 1/Km = affinity) is higher in the presence of the competitive inhibitor
NONCOMPETITIVE INHIBITOR
- Binds at a site ? from the substrate (aka ? site)
- It can bind the free enzyme or the ES complex
-> ** preventing the ? from occurring ** - Causes ? in enzyme or active site of the enzyme → inhibition
- also decreases the ? of the reaction (↑ [S] does not reverse it – why?)
Km remains unchanged as noncompetitive inhibitors ? (2nd graph in pic)
These effects can be readily seen when plotting these in a Lineweaver-Burk plot
NONCOMPETITIVE INHIBITOR
- Binds at a site different from the substrate (aka ? site)
- It can bind the free enzyme or the ES complex
-> ** preventing the rxn from occurring ** - Causes conformational change in enzyme or active site of the enzyme → inhibition
- also decreases the Vmax of the reaction (↑ [S] does not reverse it – why?)
Km remains unchanged as noncompetitive inhibitors do not interfere with the binding of the substrate to the enzyme (2nd graph in pic)
These effects can be readily seen when plotting these in a Lineweaver-Burk plot! (straight line plot - note that on the x axis Km of both the lines meet at the same point)
COENZYMES
* Coenzymes are often derived from ?.
* Can be either ? or ? bound to the enzyme.
* Are associated with the ? that assists with their catalytic function.
* Vitamins cannot be synthesized by humans and most animals; and must be supplied from the ?.
* Many vitamins are essential components of enzymes or provide those as ?
COENZYMES - Biotin
Recall:
involved in FA synthesis as its required in the carboxylation process - from ACoA to malonyl CoA (but biotin can also help with other carboxylases such as below:)
Attached to distinct ? residues in histones, affecting ? structure and mediating ?
(epigenetic modification)
COENZYMES
* Coenzymes are often derived from vitamins
* Can be either loosely or tightly bound to the enzyme.
* Are associated with the enzyme’s active site that assists with their catalytic function.
* Vitamins cannot be synthesized by humans and most animals; and must be supplied from the diet.
* Many vitamins are essential components of enzymes or provide those as coenzymes
COENZYMES - Biotin: Attached to distinct lysine residues in histones, affecting chromatin structure and mediating gene regulation
(epigenetic modification)
ZYMOGENS
Proteolytic cleavage = ?
For the cleavage, ? (ATP) is needed or not needed?
Proteins (enzymes) located outside cells can be activated by ?.
Proteolytic cleavage occurs ? in the life of an enzyme molecule, the process is ? (Unlike allosteric control and reversible covalent)
Zymogen aka ? either have the suffix -? or the prefix ?
The ? are synthesized as zymOGEN or PROenzyme in the ? and ?
Cascade of events regulating digestive enzymes
1. at the beginning of intestine , enterocytes secrete x? which is the active enzyme form of Proenteropeptidase
- then x? converts trypsinogen into ? which in turn can activate trypsinogen again or help convert the proenzymes/zymogens below into their active form
- Chymotrypsinogen -> chymotrypsin
Proelastase -> elastase
ProcarboxypeptidasesA and B -> carboxypeptidases A and B
Pancreatic prolipase -> pancreatic lipase - In the stomach, ? is secreted which helps convert proteins into ?
- the large peptides then get broken down into small peptides with the help of which 3 enzymes?
- the small peptides get broken down into free AAs and triglycerides with the help of which 3 enzymes?
ZYMOGENS
Proteolytic cleavage = activation
For the cleavage, energy (ATP) is not needed!
Proteins (enzymes) located outside cells can be activated by proteolytic cleavage
Proteolytic cleavage occurs only once in the life of an enzyme molecule, the process is irreversible (Unlike
allosteric control and reversible covalent)
Zymogen aka proenzyme either have the suffix -OGEN or the prefix PRO
The digestive enzymes that hydrolyze proteins are synthesized as zymOGEN or PROenzyme in the stomach (pepsinogen) and pancreas (chymotrypsinogen, procarboxypeptidases, trypsinogen, proelastase)
Cascade of events regulating digestive enzymes
1. at the beginning of intestine , enterocytes secrete enteropeptidase which is the active enzyme form of Proenteropeptidase
- then “ ** enteropeptidase converts trypsinogen into TRYPSIN which in turn can activate trypsinogen again or help convert the proenzymes/zymogens below into their active form **
- Chymotrypsinogen -> chymotrypsin
Proelastase -> elastase
ProcarboxypeptidasesA and B -> carboxypeptidases A and B
Pancreatic prolipase -> pancreatic lipase - In the stomach, pepsin (An active form of pepsinogen) is secreted which helps convert proteins into large peptides
- the large peptides then get broken down into small peptides with the help of elastase, carboxypeptidases A and B, chymotrypsin
- the small peptides get broken down into free AAs and triglycerides with the help of aminopeptidases, dipeptidases and tripeptidases
ZYMOGEN - APOPTOSIS
?, or ?, is mediated by proteolytic enzymes called ?, which are synthesized as zymogens (precursor form as procaspases)
Unlike necrosis (traumatic cell death), apoptosis is ? and does not cause ?
When activated, caspases function to cause ? in most multicellular organisms. It produces special cell fragments (?), which are cleared by macrophages.
ZYMOGEN - APOPTOSIS
initiator caspases -> executioner caspases
kill the cell by ? proteins indiscriminately (Cannot stop once it has begun.)
Can be initiated through: (from inside of cell or outside of cell)
* ? pathway
* ? pathway
Both pathways use ? (proteases)
ZYMOGEN - APOPTOSIS
programmed cell death, or apoptosis, is mediated by proteolytic enzymes called caspases, which are synthesized as zymogens (precursor form as PROCASPASES)
Unlike necrosis (traumatic cell death), apoptosis is highly regulated and does not cause inflammation
When activated, caspases function to cause cell death in most multicellular organisms. It produces special cell fragments (apoptic bodies), which are cleared by macrophages.
ZYMOGEN - APOPTOSIS
initiator caspases -> executioner caspases
kill the cell by degrading proteins indiscriminately (Cannot stop once it has begun.)
Can be initiated through: (from inside of cell or outside of cell)
* intrinsic pathway
* extrinsic pathway
Both pathways use caspases (proteases)
REGULATION OF ENZYME ACTIVITY
ALLOSTERIC ENZYMES
? effector
? effector
- Modify ? (Vmax)
- Effectors can influence ? of enzyme for its substrate (K 0.5)
- Both (or can regulate both depending on which ? talking about)
REGULATION OF ENZYME ACTIVITY ALLOSTERIC ENZYMES
* Homotropic effectors: when the ? serves as an effector
(e..g when oxygen binds to one of the heme group the affinity for O increases thus homotropic effectors, own thing increasing affinity)
- Most allosteric substrates function as ?: the presence of the substrate molecule at one site of the enzyme enhances the catalytic properties of the other ? sites.
From: Harvey. Biochemistry
* ? is a homotropic allosteric protein
REGULATION OF ENZYME ACTIVITY
ALLOSTERIC ENZYMES
positive effector
negative effector
- Modify maximal catalytic activity (Vmax)
- Effectors can influence affinity of enzyme for its substrate (K 0.5)
- Both (or can regulate both depending on which ? talking about)
REGULATION OF ENZYME ACTIVITY ALLOSTERIC ENZYMES
* Homotropic effectors: when the substrate itself serves as an effector
(e..g when oxygen binds to one of the heme group the affinity for O increases thus homotropic effectors, own thing increasing affinity)
- Most allosteric substrates function as positive homotropic effectors: the presence of the substrate molecule at one site of the enzyme enhances the catalytic properties of the other substrate binding sites.
From: Harvey. Biochemistry
* hemoglobin is a homotropic allosteric protein
REGULATION OF ENZYME ACTIVITY
ENZYME SYNTHESIS
Cells can alter the rates of enzymes ? or ?.
Enzymes subject to synthesis regulation are often those that are needed at ? or under ?
Induction or repression of protein synthesis are ? (? to ?), compared with allosteric or covalent regulation of enzyme activity.
REGULATION OF ENZYME ACTIVITY - Summary
* Regulation of allosteric enzymes
* Covalent modification of enzymes
* Induction or repression of enzymes synthesis
REGULATION OF ENZYME ACTIVITY
ENZYME SYNTHESIS
Cells can alter the rates of enzymes synthesis or degradation.
Enzymes subject to synthesis regulation are often those that are needed at only one stage of life development or under certain physiological conditions
Induction or repression of protein synthesis are slow (hours to days), compared with allosteric or covalent regulation of enzyme activity.
