Chapter 9 ENZYMES: Regulation of Activities Flashcards
describe the ability of animals to maintain a constant intracellular environment despite changes in their
external surroundings
homeostasis
the causative agent of plague, elaborates a protein-tyrosine phosphatase that hydrolyzes phosphoryl groups on key cytoskeletal proteins.
Yersinia pestis
the causative agent of cholera, disables sensor-response pathways in intestinal epithelial cells by ADP-ribosylating the GTP-binding proteins (G-proteins) that link cell surface receptors to adenylyl cyclase
Vibrio cholerae
The ability of enzymes to discriminate between the structurally similar coenzymes NAD+ and NADP+ also results in a form of ______
compartmentation
Decreasing the catalytic efficiency or the quantity of
the catalyst responsible for the ____ will immediately reduce metabolite flux through the
entire pathway.
“bottleneck” or rate-limiting reaction
Schoenheimer deduced that proteins exist in a state of “dynamic equilibrium” within our bodies where they are continuously synthesized and degrade
protein turnover
The synthesis of certain enzymes depends upon the presence of ____, typically substrates or structurally related compounds that stimulate the transcription of the gene that encodes them
inducers
an excess of a metabolite may curtail synthesis of its cognate enzyme via ____
repression
activity is controlled by the interaction of hormones and other extracellular signals with specific cell-surface receptors
transcription factors
Proteins are targeted to the interior of the proteasome by _____, the covalent attachment of one or more ubiquitin molecules.
ubiquitination
is catalyzed by a large family of enzymes called E3 ligases, which attach ubiquitin to the sidechain amino group of lysyl residues.
Ubiquitination
is responsible both for the regulated degradation of selected cellular proteins, for example, cyclins, and for the removal of defective or aberrant protein species.
ubiquitin-proteasome pathway
refers to the process by which the end product of a multistep biosynthetic pathway binds to and
inhibits an enzyme catalyzing one of the early steps in that
pathway
Feedback inhibition
- bind small, physiologically important molecules to modulate enzymes
- Usually contain multiple subunits and frequently catalyze the committed step early in a pathway
Allosteric Enzymes
the catalyst for the first reaction unique to pyrimidine biosynthesis, is a target of feedback regulation by two nucleotide triphosphates: cytidine triphosphate (CTP) and adenosine triphosphate
Aspartate transcarbamoylase (ATCase)
are those for which catalysis at the active site may be modulated by the presence of effectors at an allosteric site
Allosteric Enzymes
a phenomenologic term devoid of mechanistic implications
feedback regulation
a mechanism for regulation of enzyme activity
feedback inhibition
Nerve impulses and the binding of many hormones to cell surface receptors elicit changes in the rate of enzyme-catalyzed reactions within target cells by inducing the release or synthesis of specialized allosteric effectors called ____
second messengers
is the hormone molecule or nerve impulse
primary or first messenger
Those effectors that increase catalytic activity are known as ___
Positive effectors ( Activators)
Effectors that reduce or inhibit catalytic activity are ___
Negative effectors (Inhibitors)
represents a classic example of epigenetics, the hereditary transmission of information by a means other than the sequence of nucleotides that comprise the genome
Histone code
Certain proteins are synthesized as inactive precursor proteins known as ___
proproteins
The proprotein forms of enzymes are termed ___
proenzymes or zymogens
involves one or more highly specific proteolytic clips that may or may not be accompanied by separation of the resulting peptides
Selective Proteolysis
The conformational changes that accompany selective proteolysis of ____ align the three residues of the charge-relay network, forming the catalytic site.
prochymotrypsin (chymotrypsinogen)
phosphorylate proteins by catalyzing transfer of the terminal phosphoryl group of ATP to the hydroxyl groups of seryl, threonyl, or tyrosyl residues, forming O-phosphoseryl, O-phosphothreonyl, or O-phosphotyrosyl residues, respectively.
Protein Kinases
The unmodified form of the protein can be regenerated by hydrolytic removal of phosphoryl groups, catalyzed by protein ____.
phosphatases
permits the functional properties of the affected enzyme to be altered only for as long as it serves a specific need
Phosphorylation-dephosphorylation
Types of Allosteric Effectors
- Heterotropic effectors - effector is different from substrate
- Homotropic effectors - the substrate itself serve as an effector
catalyze the transfer of the acetyl group of acetyl-CoA to the ε-amino groups of lysyl residues, forming N-acetyl lysine
Lysine acetyltransferases
catalyze the removal by hydrolysis of acetyl groups, regenerating the unmodified form of the protein and acetate as products
histone deacetylases
use NAD+ as substrate, which yields O-acetyl ADP-ribose and nicotinamide as products in addition to the unmodified protein
Sirtuins
targets multiple proteins in a pathway
Acetylation-deacetylation
A mechanism of regulating enzyme activity is to sequester enzymes in compartments where access to their substrates is limited
Enzyme sequestration
Inactive proenzymes are activated by ___
proteolysis
- A substance that kills bacteria or inhibits their growth
- Exert their action on bacteria and do not affect the host organism
- Usually inhibits specific enzymes essential to the life process of bacteria
Antibiotics
- The first antibiotic discovered by the German Gerhard Domagk
- Inhibits bacterial growth by its competitive inhibition of PABA conversion to folate, which is essential for normal DNA synthesis
- Humans are not affected because we do not use PABA for folate synthesis. We derive folate from our diet
Sulfa Drugs
- Discovered by Alexander Fleming while he was working with staphylococci
- inhibits transpeptidase, an enzyme essential for bacterial cell wall synthesis
Penicillin
- One of the best broad-spectrum antibiotics
- Inhibits the enzyme DNA gyrase, which is essential for removing “kinks” formed in bacterial DNA during replication
Ciprofloxacin
The final product (E) inhibits the step from A to B
Simple feedback inhibition
Both final products (D,E) inhibit the first step of their own synthesis together
Cooperative feedback inhibition
