Ch 17 Krebs Cycle 2

·         Conversion of pyruvate into acetyl CoA by __ is the link between __ and __ because __ is the fuel for the CAC; all fuels are metabolized to __ or components of the CAC
·         The CAC begins with the __--> __ and __are the products

o   Citrate synthase catalyzes this __ followed by __
§  Oxaloacetate first condenses with acetyl coA to form __, a molecule that is energy rich because it contains the __ that originated in acetyl CoA
·         Hydrolysis of __to __ and __ drives the overall reaction far in the direction of the synthesis of citrate
o   The hydrolysis of the __powers the synthesis of a new molecule from two precursors

·         Citrate synthase prevents __
o   Each active site of citrate synthse (a dimer) is located in a __between the large and small domains of a subunit, adjacent to the subunit interface
o   The enzyme undergoes __ in the course of catalysis
§  Citrate synthase exhibits __; __binds first, followed by __

·         Oxaloacetate induces a major structural rearrangement leading to the __
o   The binding of oxaloacetate does what?
§  In each subunit, the small domains do what?
• Movements as large as __ are produced by the __ elicited by quite small shifts of the __
o These structural changes create a __

·         Citrate synthase catalyzes the __ by doing what?
o   The __ and __ of __ transforms acetyl CoA into an __, which goes on to __. 
§  The newly formed __ induces more structural changes in the enzyme,c ausing the active site to become __. The enzyme cleaves the __ by __. __leaves the enzyme, followed by __, and the enzyme returns to the initial open conformation. 

·         Essentially, citrate synthase can hydrolyze __ but not __. It discriminates against the two because, first, __; and, second, __. This is __ again

·         Because the hydroxyl group is not in a right place, citrate is __into __to enable the six-carbon unit to undergo __
o   The __ is accomplished by a __ followed by a __. The result is the interchange of an H and an OH
§  The enzyme catalyzing both steps is called __, which is an __ protein that contains iron not bound to heme

·         Its four iron atoms are bound to __ and __, leaving one __ available to bind citrate through one of its COO- groups and an OH group.
o   This __ participates in __ and __ the bound substrate 

·         The first of four oxidation-reduction reactions in the CAC is catalyzed by __; it is the __ of __. Int his reaction, __is lost and __ is formed.
o   This first oxidation generates the first __

·         The second __ is the second step, the formation of __ from __, which is catalyzed by __, an organized assembly of three kinds of enzyme that has a similar mechanism to the pyruvate dehydrogenase complex
o   Both reactions include the __of an __ and the subsequent formation of a __ with __that has a __. 

·         __ is an energy rich thioester compound. In the __ reaction, the cleavage of the __ powers the synthesis of the __ from the __ and the __
o   The cleavage of the __ is coupled to the __
§  This reaction is readily reversible and is catalyzed by __

·         This reaction is the only step in the CAC that yields a compound with __
o   In mammals, there are two __ of the enzyme, one for __ and one for __
§  __ have the GTP one; __have the ATP form
·         The GDP requiring enzyme works in the __; used to power __

·         The enzyme __ catalyzes the reaction: GTP+ ADPßà GDP + ATP
·         The mechanism of __ has energy in the __; and, this energy is transformed into __
o   Step one: __ by __, which generates __
§  A histidine acts as a __that does what?

·         __ is an __; a phosphoryl group is transferred first to __ bound in the __ and then to an __ in the __
o   Each subunit has two domains
§  The amino-terminal domains have different structures
·         Alpha forms a __, binding __ of succinyl CoA synthetase
·         Beta  is an __, which binds and activates ADP

·         Reactions of four-carbon compounds is the final stage: __
o   A __ is converted into a carbonyl group in three steps: __
§  __is regenerated and more enery is extracted as __ and __

·         Succinate is oxidized to __by __, passing electrons to __because the free-energy change is insufficient to reduce NAD+.
o   FAD is always the electron acceptor in oxidations that remove __ from a substrate
§  In __, the isoalloxazine ring of FAD is covalently attached to a histidine side chain of the enzyme

o   Succinate dehydrogenase is an __ proteins ahd have __
§  It is in the __ and directly associated with the __, the link between the CAC and ATP formation
·         __produced by oxidation of succinate like NADH in other reactions; instead, __ are transferred from __directly to __of the enzyme, which passes the electrons to __, which passes them to xygen

·         The next step is the __.
o   __catalyzes the __ addition of H+ and OH-. The OH- group adds to only one side of the double bond of fumarate. So, only the __ is formed
·         Finally, __is oxidized to __by __and __ is the hydrogen acceptor

·         The net reaction of the CAC is:

Summary 
o   Two carbon atoms enter the cycle and condense with __. Two carbon atoms leave the cycle in the form of __int eh successive __ catalyzed by __ and __

o   __ leave the cycle in four oxidation reactions. Two __molecules are reduced in the oxidative decarboxylations of __, one __molecule is reduced in the __, and one __ is reduced in the oxidation of __

o   One compound with __, usually ATP, is generated from the cleavage of the __
o   Two __ are consumed: one in the __ and the other in the __

·         __ revealed that the two carbon atoms that enter each cycle are not what, but what?; they remain __
o   The two carbons that enter the cycle will be released as __in subsequent trips through the cycle
·        

Evidence shows that the enzymes of the CAC are __, enhancing the efficiency of the CAC due to __; the structure is called a __

·         The ETC oxidizes the __ and __ formed in the CAC. The transfer of electrons from the carriers to oxygen leads to the __ across the __; the __ powers the generation of ATP
o   2.5 ATP per NADH; 1.5 ATP per FADH2

§  __ are generated when the ETC oxidizes __ and __, and one high-transfer potential phosphoryl group is directly formed in one round of the CAC
·         Thus, one __ generates approximately 10 molecules of ATP

·         The CAC cycles only under aerobic conditions because __ can be regenerated in the mitochondrion only by the __
o   Glycolysis has both an aerobic and anaerobic mode, whereas the CAC is strictly __