Ch 10.2-.3 Text

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Ch 10.2-.3 Text
2014-10-22 16:29:35
Test Three
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  1. Isozymes Provide a Means of __Specific to __ and __

    ·         Isozymes are __; they display different __, or __. They are encoded by __, which usually arise through  __ and __
    • Regulation 
    • Distinct Tissues and Developmental Stages

    • enzymes that differ in amino acid sequence yet catalyze the same reaction
    • kinetic parameters, like KM
    • respond to different regulatory molecules
    • different genes
    • gene duplication and divergence
  2. ·         The existence of isozymes permits the __ to meet the needs of a given tissue or developmental stage
    o   Ex: lactate dehydrogenase (LDH) catalyzes a step in __ and __. Humans have __for this enzyme: the __ and the __. They are __ identical. Each functional enzyme is __, and many different combos of the two __polypeptide chains are possible. 
    • fine-tuning of metabolism
    • anaerobic glucose metabolism and glucose synthesis
    • two isozymic polypeptide chains 
    • H isozyme is highly expressed in heart muscle and the M isozyme is expressed in skeletal muscle
    • 75%
    • tetrameric
    • isozymic
  3. §  The __, found in the heart, has a __ than does the __. The two isozymes also differ in that __. The other combos, like H3M, have intermediate properties. 
    • H4 isozyme
    • higher affinity for substrates
    • M4 isozyme

    high levels of pyruvate allosterically inhibit the H4 but not the M4 isozyme
  4. ·         A donor molecule provides the __being attached. Most modifications are __, such as __ and __.
    o   The __ and __ enzymes are themselves regulated by __, showing that the __ of a protein can be controlled by the __ of the modifying enzymes
    • functional moiety 
    • reversible
    • phosphorylation and dephosphorylation and acetylation and deacetylation
    • acetyltransferase and deacetylase
    • phosphorylation
    • covalent modification
    • covalent modification
  5. ·         Modification isn’t always __, such as adding __ for __, such as __(a GTPase) and __(a protein tyrosine kinase), to become __, allowing them to better __ and __ info that is being passed along their __.

    • reversible
    • lipid groups for signal-transduction pathways
    • Ras 
    • Src 
    • affixed to the cytoplasmic face of the plasma membrane
    • receive and transmit info
    • signaling pathways
  6. o   Attachment of the small protein __can signal that a protein is to be destroyed, the ultimate means of regulation. The protein __must be __and destroyed before a cell can enter __and proceed through the cell cycle
    • ubiquitin 
    • cyclin 
    • ubiquinated 
    • anaphase
  7. ·         __ and __ control the extent of __
    o   As much as 30% of eukaryotic proteins are __ by __, one of the largest families; it allows regulation to be what
    • Kinases and phosphatases
    • protein phosphorylation
    • phosphorylated by protein kinases
    • fine-tuned according to a specific tissue, time, or substrate
  8. ·         ATP is the most common donor of __. The terminal group of ATP is transferred to a __, which is commonly __, __, or __. Transfers to __ and __ residues are handled by one class of protein kinases and to __residues by another.
    o   Tyrosine kinases play pivotal roles in growth regulation, and mutations in these enzymes are commonly observed in cancer cells
    • phosphoryl groups
    • specific amino acid
    • commonly serine, threonine, and tyrosine
    • serine and threonine
    • tyrosine
  9. The acceptors in __ are located inside cells, where the __is abundant. Proteins that are entirely extracellular are not regulated by __.
    • protein-phosphorylation reactions
    • phosphoryl-group donor ATP 
    • reversible phosphorylation
  10. ·         Protein kinases vary in their degree of __
    o   Dedicated protein kinases phosphorylate a __ or __
    o   __ modify many targets; they have a wide reach and can coordinate diverse processes
    §  A __ recognizes related sequences. For example, the __ recognized by __ is __, where X is a __ and Z is a __, and __ and __ are the sites of __
    ·         This sequence is not required. Lysine can sub for one of the Arg residues, with a decrease in affinity
    • specificity
    • single protein or several closely related ones
    • Multifunctional protein kinases
    • multifunctional kinase
    • consensus sequence
    • protein kinase A (PKA)
    • Art-Arg-X-Ser/Thr-Z
    • small residue
    • large hydrophobic one
    • Ser and Thr
    • phosphorylation
  11. §  Short synthetic peptides containing a __ are nearly always __by __. Thus, the __ is the __ surrounding the __.
    ·         Distant residues can, however, contribute to __.
    • consensus motif
    • phosphorylated 
    • serine-threonine protein kinases
    • primary determinant of the specificity
    • amino acid sequence
    • serine or threonine phosphorylation site
    • specificity
  12. ·         Protein phosphatases do what and how? The enzyme does what?
    o   The unmodified __is regenerated and __is produced. These enzymes play a vital role in cells because they __ that are activated by __.
    • reverse the effects of kinases by catalyzing the removal of phosphoryl groups attached to proteins
    • hydrolyzes the bond attaching the phosphoryl group
    • hydroxyl-containing side chain 
    • orthophosphate 
    • turn off signaling pathways
    • kinases
  13. ·         __ and __ are not the reverse of each other; both are irreversible and take place at negligible rates without the enzyme
    o   So, __will take place only through the action of a specific __ and at the expense of __, and __will take place only through the action of a __
    §  Result: target proteins cycle __between __ and __ forms; the __ depends on the activities of __ and __
    • Phosphorylation and dephosphorylation
    • phosphorylation 
    • protein kinase
    • ATP cleavage
    • dephosphorylation 
    • phosphatase
    • unidirectionally 
    • unphosphorylated and phosphorylated
    • rate of cycling
    • kinases and phosphatases
  14. ·         Reasons why phosphorylation is a highly effective means of controlling the activity of proteins
    • o   The free energy is large; and, it can change the conformational equilibrium between different functional states
    • o   A phosphoryl group adds two negative charges to a modified protein, disrupting electrostatic interactions and forming new ones
    • o   A phosphoryl group can form three+ hydrogen bods. These bonds are highly directional
    • o   Phosphorylation and dephosphorylation can take place in less than a second
    • o   Phosphorylation often evokes highly amplified effects
    • o   ATP is the cellular energy currency
  15. ·         __ activates __ by altering the __

    • Cyclic AMP
    • protein kinase A
    • quaternary structure
  16. What is cAMP?
    o cAMP is an intracellular messenger formed by cyclization of ATP; and, it activates a key enzyme, PKA, which alters the activities of target proteins by phosphorylating specific serine or threonine residues.
  17. §  Most effects of cAMP in eukaryotic cells are achieved through __
    ·         __is activated by __concentrations near 10 nM; it has __.
    o   In the absence of cAMP, what happens?    
    activation by cAMP of PKA

    • PKA 
    • cAMP 
    • two subunits—a 49 kD regulatory subunit and a 38 kd catalytic subunit

    the regulatory and catalytic subunits form an R2C2 complex that is enzymatically inactive
  18. §  When two molecules of __bind to each of the regulatory subunits, the __ dissociates into an __ and __. These free catalytic subunits are then active.
    ·         Thus, the binding of cAMP to the regulatory subunit does what?
    o   __and most other kinases exist in __ fo __ to meet the needs of a specific cell or developmental stage
    • two
    • cAMP 
    • R2C2
    • R2 subunit and two C subunits

    • relieves its inhibition of the catalytic subunit
    • PKA 
    • isozymic forms for fine-tuning regulation
  19. ·         How does the binding of cAMP activate the kinase?
    • o   Each R chain contains the sequence Arg-Arg-Gly-Ala-Ile, which matches the consensus sequence for phosphorylation except for the presence of alanine in place of serine. In the R2C2 complex, the pseudosubstrate sequence of R occupies the catalytic site of C, thereby preventing the entry of protein substrates
  20. § The binding of cAMP to the R chains does what?

    § The released __ are then free to __ and __.
    • allosterically moves the pseudosubstrate sequences out of the catalytic sites
    • C chains
    • bind and phosphorylate substrate proteins
  21. ·         ATP and the target protein do what?
    o   The 350-residue catalytic subunit of __has two lobes. __ and __ fill a deep cleft between the lobes. The __lobe makes many contacts with __, whereas the larger lobe binds the peptide and contributes the key catalytic residues. 
    • bind to a deep left in the catalytic subunit of PKA
    • PKA 
    • ATP and part of the inhibitor
    • smaller 
    • ATP-Mg2+
  22. §  As with other kinases, the two lobes move closer to one another on __; mechanisms that restrict this domain closure provide the __
    ·         The PKA structure has broad significance because residues 40 to 280 constitute a __that is common to all known protein kinases
    • substrate binding
    • regulation
    • conserved catalytic core