Chapter 16: Glycogen Metabolism and Gluconegenesis Flashcards
difference between glucose and glycogen
Glucose is a single sugar unit or monosaccharide. Glycogen is a multi-sugar unit or polysaccharide
function of glycogen and starch?
Store glucose for metabolic use
Glycogen broken down so it can enter glycolysis
In animals, a constant supply of glucose is essential for tissues such as?
the brain and red blood cells which depend almost entirely on glucose as an energy source
The mobilization of glucose from glycogen stores, primarily in where?, provides a constant supply of how much glucose to all tissues.
Liver
(~5 mM in blood)
When glucose is plentiful, such as immediately after a meal, glycogen synthesis accelerates. Yet the liver’s capacity to store glycogen is sufficient to supply the brain with glucose for only about half a day. Under fasting conditions, most of the body’s glucose needs are met by what?
gluconeogenesis (literally, new glucose synthesis) from noncarbohydrate precursors such as amino acids.
structure of glycogen? its branched at how many residues
α(1→4)-linked D-glucose with α(1→6)-linked branches every 8–14 (10) residues, highly branched
why is it alpha
hydroxyl groups on the bottom
How and where are glucose units mobilized,
What allows rapid mobilization of large amounts of glucose
Glucose units are mobilized by their sequential removal from the nonreducing ends of glycogen (the ends lacking a C1-OH group).
remove glucose from non reducing ends
allows rapid mobilization of large amounts of glucose
difference between non reducing and reducing end?
reducing end - aldehyde/acetal can be relatively easily oxidized
nonreducing end- not an aldehyde
what is glycogenolysis?
the breakdown of glycogen
List the three enzymes involved in glycogen degradation and describe the type of reactions they catalyze.
1.Glycogen phosphorylase (or simply phosphorylase) catalyzes glycogen phosphorolysis (bond cleavage by the substitution of a phosphate group) to yield glucose-1-phosphate (G1P)
Leaves a limit branch
2. Glycogen debranching enzyme removes glycogen’s branches, thereby making additional glucose residues accessible to glycogen phosphorylase.
- Phosphoglucomutase converts G1P to G6P, which has several metabolic fates (
Glucose mobilization in the liver involves a series of conversions from glycogen to glucose-1-phosphate to glucose-6-phosphate and finally to glucose.
difference between glycogen phosphorylase a and b
glycogen phosphorylase a at Ser14 is more active
glycogen phosphorylase b is less active it is dephosphrylated
Glycogen Debranching Enzyme function?
What does the The α(1 → 6) bond/ branch left behind convert to?
is it slow or faster than glycogen phosphorylase
acts as an 𝛂(1 → 4) transglycosylase/Glucosyltransferase by transfer of an α(1→4)-linked trisaccharide from a limit branch of glycogen to a nonreducing end.
forms a new α(1 → 4) linkage with three more units available for further phosphorolysis.
branch left behind is hydrolyzed and forms glucose instead of G1P
takes glucoses and break them off of branch and add to another chain to form chain long enough for glycogen phosphorylase to continue
debranching much slower than glycogen phopsphorylase reaction
Phosphoglucomutase Function
Interconverts Glucose-1-Phosphate and Glucose-6-Phosphate
A phosphoryl group is transferred from the active phosphoenzyme to G1P, forming glucose-1,6-bisphosphate (G1,6P), which then rephosphorylates the enzyme to yield G6P
difference between Phosphoglucomutase and phosphoglycerate mutase?
the phosphoryl group in phosphoglucomutase is covalently bound to a Ser hydroxyl group rather than to a His imidazole nitrogen.
The fates of G6P.
synthesize glycogen, pentose pathway, or glycolysis
also in liver where it can be converted to glucose for export to tissues via blood
why must glycogen synthesis and breakdown occur by separate pathways.
glycogen breakdown is exergonic and the synthesis of glycogen from G1P under physiological conditions is therefore thermodynamically unfavorable without free energy input.
- List the three enzymes involved in glycogen synthesis
UDP–glucose pyrophosphorylase, glycogen synthase, and glycogen branching enzyme.
UDP–Glucose Pyrophosphorylase function
glycogen biosynthesis requires an exergonic step. This is accomplished, by combining G1P with uridine triphosphate (UTP) in a reaction catalyzed by UDP–glucose pyrophosphorylase.
The product of this reaction, uridine diphosphate glucose (UDP–glucose or UDPG).
What is UDPG
an “activated” compound that can donate a glucosyl unit to the growing glycogen chain.
Glycogen synthase cannot simply link together two glucose residues; it can only extend an already existing α(1 → 4)-linked glucan chain. How, then, is glycogen synthesis initiated
Glycogen synthase only extends existing chains.
Glycogenin
is glycosylated on a Tyr residue by tyrosine glycosyltransferase. Glycogenin can extend chain by up to seven residues, using UDPG.
Glycogenin Primes Glycogen Synthesis.
Glycogen Synthase function?
Extends Glycogen Chains
Glycogen synthase adds glucosyl units to the nonreducing ends of a growing glycogen molecule that has been primed by glycogenin.
Glycogen is extended from a primer built on and by the protein glycogenin.
Glycogen Branching Enzyme function for glycogen synthesis?
Glycogen Branching Enzyme Transfers Seven-Residue Glycogen Segments
A branch is created by transferring a 7-residue segment from the end of a chain to the C6-OH group of a glucose residue on the same or another glycogen chain
Glycogen synthase generates only α(1 → 4) linkages to yield α-amylose. Branching to form glycogen is accomplished by this enzyme
difference between glycogen synthase a and glycogen synthase b
glycogen synthase a dephosphorylated
is more active
glycogen synthase b phosphorylated
is less active
Why is glucose stored in form of glycogen?
To avoid “osmotic stress” (high osmotic pressure).
Osmotic pressure is a colligative property, i.e. it is dependent on the number of dissolved particles, not on their properties (such as size).
Concentration of glycogen in liver cell ≈ 10 nM Concentration of glucose contained in glycogen ≈ 0.4 M
The opposing processes of glycogen breakdown and synthesis are reciprocally regulated by what 3 things?
The regulation of glycogen metabolism involves allosteric control as well as hormonal control by covalent modification of the pathway’s regulatory enzymes.
substrate cycling as well
What two enzymes in glycogen synthesis and degradation are under allosteric control and covalent modification?
Glycogen Phosphorylase and Glycogen Synthase
Why are glycogen synthesis and breakdown controlled?
to make Sure they don’t run simultaneously
Glycogen metabolism is ultimately under the control of hormones such as ?
insulin, glucagon, and epinephrine.
Both glycogen phosphorylase and glycogen synthase are under allosteric control by effectors that include?
ATP, G6P, and AMP.
What is glycogen phosphorylase activated and inhibited by?
Muscle glycogen phosphorylase is activated by AMP and inhibited by ATP and G6P
What is glycogen synthase activated and inhibited by?
Glycogen synthase, on the other hand, is activated by G6P.
when there is high demand for ATP (low [ATP], low [G6P], and high [AMP]), which is stimulated glycogen phosphorylase or glycogen synthase? How about when when [ATP] and [G6P] are high,
when there is high demand for ATP (low [ATP], low [G6P], and high [AMP]), glycogen phosphorylase is stimulated and glycogen synthase is inhibited, which favors glycogen breakdown. Conversely, when [ATP] and [G6P] are high, glycogen synthesis is favored.
The interconversion of the a and b forms of glycogen synthase and glycogen phosphorylase is accomplished through enzyme-catalyzed what?
phosphorylation and dephosphorylation a process that is under hormonal control.
What are the effects of phosphorylation and dephosphorylation on glycogen phosphorylase and glycogen synthase? (covalent modification)
glycogen phosphorylase is activated by phosphorylation (b → a), whereas glycogen synthase is inactivated by phosphorylation (a → b). Conversely, dephosphorylation inactivates glycogen phosphorylase and activates glycogen synthase.
The cascade that governs the enzymatic interconversion of glycogen phosphorylase involves what three enzymes
- Phosphorylase kinase, which specifically phosphorylates Ser 14 of glycogen phosphorylase b.
- Protein kinase A (PKA; Section 13-3C), which phosphorylates and thereby activates phosphorylase kinase. and, thus, stimulates glycogen breakdown)
- Phosphoprotein phosphatase-1 (PP1; Section 13-2D), which dephosphorylates and thereby deactivates both glycogen phosphorylase a and phosphorylase kinase.
What activates PKA
cAMP
what activates phosphorylase kinase, therefore , glycogen phosphorylase
Ca 2+binding to calmodulin
and phosphorylation
Ca 2+ triggers muscle contractions, and, by activating glycogen phosphorylase, provides glucose to fuel these contractions
Through dephosphorylation, PP1 reduces activity of ?
glycogen phosphorylase and phosphorylase kinase by
2 enzymes that regulate glycogen synthase
by PKA and other kinases phosphorylate and thereby inactivate glycogen synthase
phosphorylase kinase (which activates glycogen phosphorylase and, thus, stimulates glycogen breakdown) does what to glycogen synthase?
phosphorylates and thereby inactivates glycogen synthase
To a large extent, the rates of the phosphorylation and dephosphorylation of these enzymes control glycogen synthesis and breakdown. The two processes are linked by
PKA and phosphorylase kinase, which, through phosphorylation, activate glycogen phosphorylase as they inactivate glycogen synthase.
They are also linked by PP1, which in liver is inhibited by phosphorylase a and therefore unable to activate (dephosphorylate) glycogen synthase unless it first inactivates (also by dephosphorylation) phosphorylase a.
Glycogen Metabolism Is Subject to Hormonal Control. Name some of the hormones
Glycogen metabolism is ultimately under the control of hormones such as insulin, glucagon, and epinephrine/adrenaline.
What is Gluconeogenesis and where does It occur?
necessary when glucose and glycogen supplies are depleted
- occurs in liver (and kidney)
When dietary sources of glucose are not available and when the liver has exhausted its supply of glycogen, glucose is synthesized from noncarbohydrate precursors (lactate, pyruvate, and amino acids.) by gluconeogenesis.
pyruvate is converted to glucose.
The 4 noncarbohydrate precursors that can be converted to glucose include?
the glycolysis products lactate and pyruvate, citric acid cycle intermediates, and the carbon skeletons of most amino acids.
What must all the noncarbohydrate precursors convert to very first thing in the reaction? (a citric cycle intermediate)
First, however, all these substances must be converted to the four-carbon compound oxaloacetate (at left), which itself is a citric acid cycle intermediate
How is gluconeogenesis related to glycolysis
Gluconeogenesis is mostly the reverse of glycolysis with the pyruvate kinase reaction bypassed by the pyruvate carboxylase and phosphoenolpyruvate carboxykinase reactions, and the phosphofructokinase and hexokinase reactions bypassed by phosphatase reactions.
and
Glycolysis and gluconeogenesis are reciprocally regulated by allosteric effects, phosphorylation, and changes in enzyme synthesis rates.
Pyruvate carboxylase and PEP carboxykinase (PEPCK) bypass pyruvate kinase, fructose-1,6-bisphosphatase (FBPase) bypasses phosphofructokinase, and glucose-6-phosphatase bypasses hexokinase.
How is pyruvate converterted to Phosphoenolpyruvate?
by first converting the pyruvate to oxaloacetate.
1. Pyruvate carboxylase catalyzes the ATP-driven formation of oxaloacetate from pyruvate and HCO 3 − .
- PEP carboxykinase (PEPCK) converts oxaloacetate to PEP in a reaction that uses GTP as a phosphoryl-group donor.
Pyruvate Carboxylase Has a Biotin Prosthetic Group
What is the problem that occurs when trying to synthesize oxaloacetate?
Glycolysis and gluconeogenesis occur in cytosol, oxaloacetate is produced in mitochondrion.
No transporter for oxaloacetate across the inner mitochondrial membrane exists.
Gluconeogenesis Requires Metabolite Transport between Mitochondria and Cytosol.
How is Gluconeogenesis regulated
Gluconeogenesis is regulated by changes in enzyme synthesis and by allosteric effectors, including fructose-2,6-bisphosphate (F2,6P), which inhibits FBPase and activates phosphofructokinase (PFK) and whose synthesis depends on the phosphorylation state of the bifunctional enzyme phosphofructokinase-2/fructose bisphosphatase-2 (PFK-2/FBPase-2).
Long-term regulation also occurs via changes in the amounts of certain enzymes. Transcription rates can be affected by hormones.
Other Carbohydrate Biosynthetic Pathways
O and N-linked oligosaccharides
Formation of glycosidic bond requires?
nucleotide sugars/energy:
How are O-Linked oligosaccharides synthesized?
O-Linked oligosaccharides are synthesized by the sequential addition of sugars to a protein.
How are N-Linked oligosaccharides synthesized?
- N-Linked oligosaccharides are assembled on a dolichol carrier and then transferred to a protein.
- attached to Asn
