C. cytoplasm, granules
Glycogen is a branched-chain polysaccharide made exclusively from α-D-glucose. The primary glycosidic bond is an α(1→4) linkage. After an average of eight to ten glucosyl residues, there is a branch containing an α(1→6) linkage . A single molecule of glycogen can have a molecular mass of up to 108 daltons. These molecules exist in discrete CYTOPLASMIC GRANULES that also contain most of the enzymes necessary for glycogen synthesis and degradation.
(Lippincott - p. 126)
A. maintain blood glucose to normal levels
(BRS Biochemistry - p. 2)
C. elongation of chains forming amylopectin chains
B. glycogenin
B. Primer requirement and synthesis
Glycogen synthase catalyzes the α(1→4) linkages in glycogen. This enzyme cannot initiate chain synthesis using free glucose as an acceptor of a molecule of glucose from UDPglucose.
Instead, it can only elongate already existing chains of glucose and, therefore, requires a primer. A fragment of glycogen can serve as a primer. In the absence of a fragment, the homodimeric protein glycogenin can serve as an acceptor of glucose from
UDP-glucose (see Fig. 11.5). The side-chain hydroxyl group of tyrosine-194 in the protein is the site at which the initial glucosyl unit is attached. Because the reaction is catalyzed by
GLYCOGENIN itself via AUTOGLYCOSYLATION, glycogenin is an enzyme. Glycogenin then catalyzes the transfer of at least four molecules of glucose from UDP-glucose, producing a short,
α(1→4)-linked glucosyl chain. This short chain serves as a primer that is able to be elongated by glycogen synthase, which is recruited by glycogenin, as described in C.
below. (Note: Glycogenin stays associated with and forms the core of a glycogen granule.)
(Lippincott Illustrated Reviews 8th Edition, p. 273)
B. A homodimer with two active sites to where glucose is attached
B. Primer requirement and synthesis
Glycogen synthase catalyzes the α(1→4) linkages in glycogen. This enzyme cannot initiate chain synthesis using free glucose as an acceptor of a molecule of glucose from UDPglucose.
Instead, it can only elongate already existing chains of glucose and, therefore, requires a primer. A fragment of glycogen can serve as a primer. In the absence of a fragment, the HOMODIMERIC protein glycogenin can serve as an acceptor of glucose from UDP-glucose (see Fig. 11.5). The side-chain hydroxyl group of tyrosine-194 in the protein is
the site at which the initial glucosyl unit is attached. Because the reaction is catalyzed by glycogenin itself via autoglucosylation, glycogenin is an enzyme. Glycogenin then catalyzes the transfer of at least four molecules of glucose from UDP-glucose, producing a short, α(1→4)-linked glucosyl chain. This short chain serves as a primer that is able to be elongated by glycogen synthase, which is recruited by glycogenin, as described in C. below. (Note: Glycogenin stays associated with and forms the core of a glycogen granule.)
(Lippincott Illustrated Reviews 8th Edition, p. 273)
C. Change G6PO4 to G1PO4, subsequent hydrolysis of
released PPi to 2 Pi
A. Uridine diphosphate glucose synthesis
α-D-Glucose attached to uridine diphosphate (UDP) is the source of all the glucosyl residues that are added to the growing glycogen molecule. UDP-glucose (Fig. 11.4) is synthesized from glucose 1-phosphate and UTP by UDP–glucose pyrophosphorylase (Fig. 11.5). Pyrophosphate (PPi), the second product of the reaction, is hydrolyzed to two inorganic phosphates (Pi) by pyrophosphatase. The hydrolysis is exergonic, which ensures that the UDP–glucose pyrophosphorylase reaction proceeds in the direction of UDP-glucose production. (Note: Glucose 1-phosphate is generated from glucose 6-phosphate by
phosphoglucomutase. Glucose 1,6-bisphosphate is an obligatory intermediate in this reversible reaction [Fig. 11.6].)
(Lippincott Illustrated Reviews 8th Edition, p. 272)
C. O-linked glycosidic bond
N- and O-glycosides:
If the group on the non-carbohydrate molecule to which the sugar is attached is an –NH2 group, the structure is an N-glycoside and the bond is called an N-glycosidic link. If the group is an –OH, the structure is an O-glycoside, and the bond is an O-glycosidic link. [Note: All sugar–sugar glycosidic bonds are O-type linkages.]
(Lippincott Illustrated Reviews 5th Edition, p. 86)
A. UTP & glucose-1-PO4
A. Uridine diphosphate glucose synthesis
α-D-Glucose attached to uridine diphosphate (UDP) is the source of all the glucosyl residues that are added to the growing glycogen molecule. UDP-glucose (Fig. 11.4) is synthesized from GLUCOSE 1-PHOSPHATE AND UTP by UDP–glucose pyrophosphorylase (Fig. 11.5). Pyrophosphate (PPi), the second product of the reaction, is hydrolyzed to two inorganic phosphates (Pi) by pyrophosphatase. The hydrolysis is exergonic, which ensures that the UDP–glucose pyrophosphorylase reaction proceeds in the direction of UDP-glucose production. (Note: Glucose 1-phosphate is generated from glucose 6-phosphate by
phosphoglucomutase. Glucose 1,6-bisphosphate is an obligatory intermediate in this reversible reaction [Fig. 11.6].)
(Lippincott Illustrated Reviews 8th Edition, p. 272)
D. UDP-Glucose-pyrophosphorylase
A. Uridine diphosphate glucose synthesis
α-D-Glucose attached to uridine diphosphate (UDP) is the source of all the glucosyl residues that are added to the growing glycogen molecule. UDP-glucose (Fig. 11.4) is synthesized from glucose 1-phosphate and UTP by ““UDP-glucose-phosphorylase”” (Fig. 11.5). Pyrophosphate (PPi), the second product of the reaction, is hydrolyzed to two inorganic phosphates (Pi) by pyrophosphatase. The hydrolysis is exergonic, which ensures that the UDP–glucose pyrophosphorylase reaction proceeds in the direction of UDP-glucose production. (Note: Glucose 1-phosphate is generated from glucose 6-phosphate by
phosphoglucomutase. Glucose 1,6-bisphosphate is an obligatory intermediate in this reversible reaction [Fig. 11.6].)
(Lippincott Illustrated Reviews 8th Edition, p. 272)
A. six
B. amylo α1,4 –> α1,6 transglucosidase
IV. Glycogenolysis
B. Branch removal
Branches are removed by the two enzymic activities of a single bifunctional protein, the debranching enzyme (see Fig. 11.8). First, oligo-α(1→4)→α(1→4)-glucantransferase activity removes the outer three of the four glucosyl residues remaining at a branch. It next transfers them to the nonreducing end of another chain, lengthening it accordingly. Thus, an ““α(1→4)”” bond is broken and an α(1→4) bond is made, and the enzyme functions as a 4:4 transferase. Next, the remaining glucose residue attached in an α(1→6) linkage is removed hydrolytically by ““amylo-α(1→6)-glucosidase activity””, releasing free (nonphosphorylated) glucose. The glucosyl chain is now available again for degradation by glycogen phosphorylase until four glucosyl units in the next branch are reached.
12.Glycogen synthase action will commence after how many glucose units have been incorporated into the tyrosine residue of each of the active sites of glycogenin?
A. six
B. eight
C. nine
D. ten
B. eight
C. phosphorolysis
Glycogen phosphorylase sequentially cleaves the α(1,4) glycosidic bonds between the glucosyl residues at the nonreducing ends of the ““glycogen”” chains by simple ““phosphorolysis”” (producing ““glucose 1-phosphate””) until four glucosyl units remain on each chain at a branch point. (Lippincott Illustrated Reviews 8th Edition, p. 396)
B. Remodeling of the glycogen molecule by the use of
debranching enzymes ???
C. four
IV. DEGRADATION (GLYCOGENOLYSIS)
A. Chain shortening
Glycogen phosphorylase sequentially cleaves the α(1→4) glycosidic bonds between the glucosyl residues at the nonreducing ends of the glycogen chains by simple phosphorolysis (producing glucose 1-phosphate) until ““four glucosyl units”” remain on each chain at a branch point (Fig. 11.7). The resulting structure is called a limit dextrin, and phosphorylase cannot degrade it any further (Fig. 11.8). (Note: Phosphorylase requires pyridoxal phosphate [a derivative of vitamin B6] as a coenzyme.)
(Lippincott Illustrated Reviews 8th Edition, p. 276)
A. AMP
IV. DEGRADATION (GLYCOGENOLYSIS)
A. Allosteric regulation of glycogenesis and glycogenolysis
2. Glycogenolysis activation by AMP: Muscle glycogen phosphorylase (myophosphorylase), but not the liver isozyme, is active in the presence of the high AMP concentrations that occur under extreme conditions of anoxia and ATP depletion. AMP binds to glycogen phosphorylase b, causing its activation without phosphorylation (see Fig. 11.9). Recall that AMP also activates phosphofructokinase-1 of glycolysis, allowing glucose from glycogenolysis to be oxidized.
(Lippincott Illustrated Reviews 8th Edition, p. 284)
B. glucose 6-PO4
IV. DEGRADATION (GLYCOGENOLYSIS)
3. Glycogenolysis activation by calcium
a. Muscle phosphorylase kinase activation: During muscle contraction, there is a rapid and urgent need for ATP. It is supplied by the degradation of muscle glycogen to ““glucose 6-phosphate’”, which enters glycolysis. Nerve impulses cause membrane depolarization, which promotes Ca2+ release from the sarcoplasmic reticulum into the sarcoplasm of myocytes. The Ca2+ binds the CaM subunit, and the complex activates muscle phosphorylase kinase b (see Fig. 11.9).
(Lippincott Illustrated Reviews 8th Edition, p. 285)
C. glucose
IV. DEGRADATION (GLYCOGENOLYSIS)
3. Glycogenolysis activation by calcium
b. Liver phosphorylase kinase activation: During physiologic stress, epinephrine is released from the adrenal medulla and signals the need for blood glucose. This ““glucose”” initially comes from hepatic glycogenolysis. Binding of epinephrine to hepatocyte α1-adrenergic GPCR activates a phospholipid-dependent cascade that results in movement of Ca2+ from the ER into the cytoplasm. A Ca2+–CaM complex forms and activates hepatic phosphorylase kinase b. Note that the released Ca2+ also helps to activate protein kinase C that can phosphorylate and inactivate
glycogen synthase a. (Lippincott Illustrated Reviews 8th Edition, p. 285-286)
A. amylo α1,4 –> α1,4 glucan transferase
IV. DEGRADATION (GLYCOGENOLYSIS)
B. Branch removal
Branches are removed by the two enzymic activities of a single bifunctional protein, the debranching enzyme (see Fig. 11.8). First, oligo-α(1→4)→α(1→4)-glucantransferase
activity removes the outer three of the four glucosyl residues remaining at a branch. It next transfers them to the nonreducing end of another chain, lengthening it accordingly. Thus, an
α(1→4) bond is broken and an α(1→4) bond is made, and the enzyme functions as a 4:4 transferase. Next, the remaining glucose residue attached in an α(1→6) linkage is removed
hydrolytically by amylo-α(1→6)-glucosidase activity, releasing free (nonphosphorylated) glucose. The glucosyl chain is now available again for degradation by glycogen phosphorylase until four glucosyl units in the next branch are reached.
D. glycogen phosphorylase, amylo 1,4 to 1,4 glucan
transferase, alpha 1,6 glucosidase
IV. DEGRADATION (GLYCOGENOLYSIS)
A. Chain shortening
Glycogen phosphorylase sequentially cleaves the α(1→4) glycosidic bonds between the glucosyl residues at the nonreducing ends of the glycogen chains by simple phosphorolysis (producing glucose 1-phosphate) until four glucosyl units remain on each chain at a branch
point (Fig. 11.7). The resulting structure is called a limit dextrin, and phosphorylase cannot degrade it any further (Fig. 11.8). (Note: Phosphorylase requires pyridoxal phosphate [a derivative of vitamin B6] as a coenzyme.)
B. Branch removal
Branches are removed by the two enzymic activities of a single bifunctional protein, the
debranching enzyme (see Fig. 11.8). First, oligo-α(1→4)→α(1→4)-glucantransferase
activity removes the outer three of the four glucosyl residues remaining at a branch. It next transfers them to the nonreducing end of another chain, lengthening it accordingly. Thus, an α(1→4) bond is broken and an α(1→4) bond is made, and the enzyme functions as a 4:4 transferase. Next, the remaining glucose residue attached in an α(1→6) linkage is removed hydrolytically by amylo-α(1→6)-glucosidase activity, releasing free (nonphosphorylated) glucose. The glucosyl chain is now available again for degradation by glycogen
phosphorylase until four glucosyl units in the next branch are reached.
(Lippincott Illustrated Reviews, p. 278-279)
B. phosphorylase kinase
???
A. protein phosphatase
V. GLYCOGENESIS AND GLYCOGENOLYSIS REGULATION
A. Covalent activation of glycogenolysis
5. Phosphorylated state maintenance: The phosphate groups added to phosphorylase kinase and phosphorylase in response to cAMP are maintained because the enzyme that hydrolytically removes the phosphate, protein phosphatase-1 (PP1), is inactivated by inhibitor proteins that are also phosphorylated and activated in response to cAMP (see Fig. 11.9). Because insulin also activates the phosphodiesterase that degrades
cAMP, it opposes the effects of glucagon and epinephrine.
B. von Gierke’s
Gluconeogenesis : Enzymes that by-pass irreversible steps
Pyruvate carboxylase
Phosphoenolpyruvate carboxykinase
Fructose-1,6-phosphatase
Glucose-6-phosphatase (Type Ia: von Gierke’s)
C. Tarui’s
Glycolysis (Irreversible Steps) : Enzymes
Hexokinase/Glucokinase
Phosphofructokinase (Rate-limiting step) : Type VII : Tauri’s
Pyruvate Kinase