Glycogen Breakdown
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Transcript of Glycogen Breakdown
Chapter 18Storage Mechanisms and Control in
Carbohydrate Metabolism
Mary K. CampbellShawn O. Farrellhttp://academic.cengage.com/chemistry/campbell
Paul D. Adams • University of Arkansas
Glycogen Breakdown
• Glycogen is cleaved by phosphate to give
• Cleavage reaction is ______________________, not hydrolysis
• No _______ is involved in reaction• Reaction is catalyzed by glycogen phosphorylase
Glycogen Breakdown
• In the second reaction, glucose-1-phosphate is isomerized to __________________________
• This reaction is catalyzed by phosphoglucomutase
• Complete breakdown requires debranching enzymes to degrade the linkages
Debranching Glycogen
How is Glycogen formed from Glucose?
• Not exact reversal of glycogen breakdown to glucose
• Glycogen synthesis requires energy
• Energy supplied by hydrolysis of ___________________
• Glucose-1-phosphate reacts with UTP to make UDPG
• Pyrophosphate is also formed• UDPG is then added to a
growing chain of glycogen, catalyzed by glycogen _______________________
How is Glycogen formed from Glucose?
• Coupling of UDPG formation with hydrolysis of ____________________________ drives formation of UDPG to completion
Reaction Catalyzed by Glycogen Synthase
Control of Glycogen Metabolism
• Glycogen phosphorylase is a major control point in the synthesis and breakdown of glycogen
• Glycogen phosphorylase activity can be allosterically controlled, as well as, controlled through _________ modification
Control of Glycogen Metabolism (Cont’d)
• The activity of glycogen synthaseglycogen synthase is subject to the same type of covalent modification as glycogen phosphorylase, but the response is opposite
• In addition:• Hormonal signals (glucagon or epinephrine) _______
its phosphorylation• After phosphorylation, glycogen synthase becomes
__________ at the same time the hormonal signal is activating phosphorylase
• Glycogen synthase can be phosphorylated by several other enzymes including phosphorylase kinase
• Dephosphorylation is by phosphoprotein phosphatase
Summary
• Glycogen is the storage form of glucose in animals, including humans. Glycogen releases glucose when energy demands are high
• Glucose polymerizes to form glycogen when the organism has no immediate need for the energy derived from glucose breakdown
• Glycogen metabolism is subject to several different control mechanisms, including covalent modification and allosteric effects
Gluconeogenesis
• Gluconeogenesis:Gluconeogenesis: pyruvate → glucose • Gluconeogenesis is __________________________
of glycolysis; that is, pyruvate to glucose does not occur by reversing the steps of glucose to pyruvate
• Three irreversible steps in glycolysis- Phosphoenolpyruvate to pyruvate + ATP
- Fructose-6-phosphate to fructose-1,6-bisphosphate
- Glucose to glucose-6-phosphate
• Net result of gluconeogenesis is reversal of these three steps, but by different __________________ and using different __________________
Oxaloacetate is an Intermediate
• In first step, pyruvate is carboxylated to oxaloacetate• Requires ________________ (CO2 carrier)
• Pyruvate carboxylase is subject to allosteric control; it is activated by _______________________
Gluconeogenesis (Cont’d)
• Next, decarboxylation of oxaloacetate is coupled with phosphorylation by ___________ to give PEP
• The net reaction of carboxylation/decarboxylation is
Pyruvate + ATP +GTP → Phosphenolpyruvate + ADP + GDP + Pi
Pyruvate Carboxlyase Reaction
Role of Sugar Phosphates
• Other different reactions in gluconeogenesis relative to glycolysis involve phosphate-ester bonds bound to sugar-hydroxyl groups being hydrolyzed
• G° = -16.7•kJ mol-1
• Fructose-1,6-bisphosphatase is an ________ enzyme, inhibited by AMP and activated by ATP
Role of Sugar Phosphates (Cont’d)
• Another reaction is the hydrolysis of glucose-6-phosphate to ___________ and _______
• Reaction also spontaneous (G°’ = -13.8 kJ mol-1)• Reaction catalyzed by glucose-6-phosphatase
Control of Carbohydrate Metabolism
Allosteric control: fructose-2,6-bisphosphate (F2,6P)• An allosteric ________ of phosphofructokinase (PFK)• An allosteric ________ of fructose bisphosphate
phosphatase (FBPase)• High concentration of F2,6P stimulates __________;
a low concentration stimulates ____________ • Concentration of F2,6P in a cell depends on the
balance between _________________ (catalyzed by phosphofructokinase-2) and _______________ (catalyzed by fructose bisphosphatase-2)
• Each enzyme is controlled by phosphorylation/dephosphorylation
Synthesis and Breakdown of F2,6P
Mechanisms of Metabolic Control
Substrate Cycling
• Substrate cycling• opposing reactions can be catalyzed by different
enzymes and each opposing enzyme or set of enzymes can be ________________________
Fructose-6-Phosphate + ATP → Fructose-1,6,-bisphosphate + ADP
Fructose-1,6,-bisphosphate + ADP → Fructose-6-Phosphate + Pi
Both Reactions are exergonic, and the net reaction is
ATP +H2O <--> ADP + Pi
Organs Share Carbohydrate Metabolism
The Cori cycle• Under vigorous ____________ ____________,
glycolysis in muscle tissue converts glucose to pyruvate; NAD+ is regenerated by reduction of pyruvate to lactate
• Lactate from muscle is transported to the _________, reoxidized to pyruvate, and converted to glucose
• The liver shares the stress of vigorous exercise
The Cori Cycle
Control Points in Carbohydrate Metabolism
• First and last steps in glycolysis are major control points in glucose metabolism
• ________________________ • Inhibited by high levels of glucose 6-phosphate• When glycolysis is inhibited through phosphofructokinase,
glucose 6-phosphate builds up, shutting down hexokinase• ________________________ (PK) is an allosteric enzyme
• Inhibited by ATP and alanine• Activated by fructose-1,6-bisphosphate
• ________________________ have 3 different subunits• M predominates in muscle, L in liver, and A in other tissues• Native PK is a tetramer• Liver isoenzymes are subject to covalent modification
Summary
• A number of control mechanisms operate in carbohydrate metabolism. These include allosteric effects, covalent modification, substrate cycles, and genetic control
• In the mechanism of substrate cycling, the synthesis and the breakdown of a given compound are catalyzed by two different enzymes
The Pentose Phosphate Pathway
• The Pentose Phosphate Pathway (PPP) is an alternative to __________________, and differs in several ways
• In glycolysis, ATP production is important, in PPP, _________________________________
• As the name implies, ____________ sugars, including ribose, are produced from glucose
• Oxidizing agent is NADP+; it is reduced to NADPH, which is a reducing agent in biosyntheses
• Begins with two oxidation steps (NADP+) to give ____________________________________
• Following this, a series of ___________________________ occur during which three-, four-, five-, six-, and seven-carbon monosaccharide phosphates are produced
The
Pen
tose
Pho
spha
te P
athw
ay
Control of the Pentose Phosphate Pathway
• The carbon-shuffling reaction are catalyzed by:• ________________________ for the transfer of
two-carbon units and• ________________________ for the transfer of
three-carbon units• Control of the PPP is maintained by:• Glucose-6-phosphate (G6P) can be channeled into
either glycolysis or the pentose phosphate pathway• G6P channeling into glycolysis, if ________________• G6P channeling into the pentose phosphate pathway,
if _________ or __________________ are needed
Group Transfer Reactions
Relationship between PPP and Glycolysis