Chapter 16: Glycogen Metabolism and Gluconeogenesis Flashcards
can function to stockpile glucose for later metabolic use
Glycogen
When glucose is plentiful, such as immediately after a meal, glycogen synthesis what?
accelerates
Under fasting conditions, most of the body’s glucose needs are met by
gluconeogenesis
is an inherited condition whose major symptom is painful muscle cramps on exertion.
McArdle’s disease
is a key branch point
Glucose-6-phosphate (G6P)
what can Glucose-6-phosphate (G6P) be used for
- synthesize glycogen
- catabolized via glycolysis to yield A TP and carbon atoms (as acetyl-CoA) which can be oxidized by the citric acid cycle
- shunted through the pentose phosphate pathway to generate NADPH and/or ribose-5-phosphate
-converted to glucose for export to other tissues via the bloodstream.
Glycogen granules are especially prominent in the cells that
make the greatest use of glycogen
what cells make the greatest use of
glycogen
muscle and liver
how mnay reducing ends does glycogen have?
one
Glucose units are mobilized by their
removal from the nonreducing ends of
glycogen
permits rapid glucose mobilization through the simultaneous release of the glucose units at the end of every branch.
Glycogen’s highly branched structure
covalently binds the cofactor
pyridoxal–5′–phosphate which is a vitamin B6 derivative
Phosphorylase
which state of Ser 14 is inactive
T -state enzyme
The conformation of phosphorylase b is
allosterically controlled
the effectors AMP, ATP, and G6P
under usual physiological conditions, the enzymatic activity of glycogen phosphorylase is largely determined by
its rates of phosphorylation and dephosphorylation.
proceeds along a glycogen branch until it approaches to within 4 or 5 residues of an α
Phosphorolysis
acts as an α(1→4) transglycosylase (glycosyltransferase) by transferring an
α(1→4)-linked trisaccharide unit from a limit branch of glycogen to the nonreducing end
of another branch.
Glycogen debranching enzyme
converted to glucose rather than G1P .
About 10% of the residues in glycogen
improves the efficiency of the debranching process.
Debranching enzyme has separate
active sites for the transferase and the α(1→6)-glucosidase reactions
cannot
pass through the cell membrane
G6P
resides in the endoplasmic reticulum (ER) membrane
G6Pase
Glucose leaves the liver cell via a specific glucose transporter named
GLUT2
The three enzymes that participate in
glycogen synthesis are
UDP–glucose pyrophosphorylase, glycogen synthase, and glycogen branching
enzyme.
attaches a glucose residue donated by UDPG to the OH group of its T yr 194.
glycogenin,
only extend an already existing α(1→4)-linked glucan chain.
Glycogen
then extends the glucose chain by up to seven additional UDPG-donated glucose residues to form a glycogen “primer”
Glycogenin
Branching to form glycogen is accomplished by
branching enzyme.
each transferred segment must
come from a chain of at least
11 residues
and the new branch point must be at leas
4 residues away from other branch points.
Both glycogen phosphorylase and glycogen synthase are under allosteric control by
effectors that include
ATP , G6P , and AMP .
Muscle glycogen phosphorylase is activated by
AMP
Muscle glycogen phosphorylase is inhibited by
ATP and G6P
when [ATP] and [G6P] are low what is favored
glycogen phosphorylase
when [ATP] and [G6P] are high what is favored
glycogen synthesis
Is Activated by Phosphorylation
and by Ca2+ concentrations
Phosphorylase Kinase
linked to the rate of muscle contraction.
rate of glycogen breakdown
are linked by PKA and phosphorylase kinase
glycogen synthesis and breakdown
PKA and phosphorylase kinase do what to glycogen synthase.
inactivate
PKA and phosphorylase kinase do what to glycogen phosphorylase
activate
is largely controlled by the polypeptide hormones insulin and glucagon acting in opposition.
Glycogen metabolism in the liver
In muscles and various tissues, control is exerted by
insulin, epinephrine, and norepinephrine.
critical for the liver’s function in supplying glucose to tissues that depend primarily on glycolysis for their energy needs
Glucagon
do not respond to glucagon because they lack the appropriate
receptor.
Muscle cells
are released into the bloodstream by the adrenal glands in response to stress.
Epinephrine and norepinephrine
two types of receptors for Epinephrine and norepinephrine
the β-adrenoreceptor (β-adrenergic receptor)
α-adrenoreceptor (α-adrenergic receptor)
whose second messenger causes intracellular [Ca2+] to increase
α-adrenoreceptor (α-adrenergic receptor)
which is linked to the adenylate cyclase system
the β-adrenoreceptor (β-adrenergic receptor)
respond to epinephrine by breaking down
glycogen for glycolysis, thereby generating
ATP
Muscle cells
respond to epinephrine directly and indirectly because epinephrine promotes the release of glucagon from the pancreas which activates glycogen phosphorylase
and inactivates glycogen synthase
Liver cells
is released from the pancreas in response to high levels of circulating glucose
Insulin
increases the rate
of glucose transport into the many types of cells that have both insulin receptors and insulin sensitive
glucose transporters
Hormonal stimulation by insulin
insulin sensitive glucose transporters called
GLUT4
decreases, causing glycogen metabolism to shift from glycogen breakdown to
glycogen synthesis by activating phosphoprotein phosphatase-1
[cAMP]
may be a messenger to which glycogen metabolism system responds.
glucose
stimulates glycogen synthesis as a result of the inhibition of glycogen synthase kinase .
insulin in the liver
promotes inactivation of glycogen phosphorylase a through its
conversion to phosphorylase b
glucose concentration
activates glycogen synthase.
release of phosphoprotein phosphatase-1
what does the liver store excess glucose as?
glycogen
When dietary sources of glucose are not available and when the liver has exhausted its supply of glycogen, glucose is
synthesized from noncarbohydrate precursors by
gluconeogenesis
The noncarbohydrate precursors that can be converted to glucose include
lactate and pyruvate,
citric acid cycle intermediates
carbon skeletons of most amino acids
both a precursor for gluconeogenesis and an intermediate of the citric acid
cycle.
Oxaloacetate
When citric acid cycle activity is low what
instead enters the gluconeogenic pathway.
oxaloacetate
Oxaloacetate is transported by
malate–aspartate shuttle system
The generation of oxaloacetate from
pyruvate or citric acid cycle intermediates
occurs only in the
mitochondrion
inhibits transcription of the gene for PEPCK,
insulin
The net energetic cost of converting two
pyruvate molecules to one glucose molecule by gluconeogenesis is
six ATP equivalents
is an extremely potent allosteric activator of
phosphofructokinase (PFK) and an inhibitor of fructose-1,6-bisphosphatase (FBPase).
Fructose-2,6-bisphosphate
whereas high concentrations of intracellular cAMP promote the transcription of the genes for
EPCK, FBPase, and glucose-6-phosphatase,
whereas high concentrations of intracellular cAMP repress the transcription of the genes for
glucokinase, PFK, and the PFK-2/FBPase-2 bifunctional enzyme.
