Mary K. Campbell
Shawn O. Farrell
http://academic.cengage.com/chemistry/campbell
Chapter 18
Storage Mechanisms and Control in
Carbohydrate Metabolism
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 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: 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 Pentose Phosphate Pathway
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