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Glycolisis and gluconeogenesis, gluconeogenesis - Coggle Diagram
Glycolisis and gluconeogenesis
Pentose-Phosphate Pathway
Stage 2
Isomerization and epimerization reactions
R5P = R5P isomerase
Xu5P = R5P epimerase
transform Ru5P to ribose-5-phosphate or xylulose-5-phosphate
3 Ru5P <-> R5P and 2Xu5P
R5P high in rapidly developing cells
Freely reversible
Stage 3
Series of C-C bond cleavage and formation reactions
Convert 2 Xu5P and 1 R5P to 2 F6P and 1 GAP
Freely reversible
F6P is a 6 carbon sugar, others are 5 carbon
3 G6P yield 3 Ru5P (C5)
Converted to 1 R5P(C3) 2 Xu5P (C6)
Uses 2 enzymes
Transketolase
Catalyses transfer of C2 Units from Xu5P to R5P
Has a thiamine pyrophosphate cofactor
Yields GAP and sedoheptulose-7-phosphate (S7P)
Transaldolase
Catalyses transfer of C3 units from S7P to GAP
Yields erythrose-5-phosphate (E4P) AND F6P
2nd transketolase reaction
Yields Glyrceraldehyde-3-phosphate (GAP) and 2nd Fructose-6-Phosphate molecule
Stage 1
Oxidative reactions which yield NADPH and ribulose-5-phosphate (Ru5P)
3 G6P 6 NADP 3 H2O
6 NADPH 6 H 3 CO2 3 Ru5P
Glucose-6-phosphate is starting point
Ru5P generates two molecules of NADPH for each molecule of G6P
Learn equation
Regulation
When need for R5P > NADPH
F6P and GAP diverted from glycolytic pathway by reversing transaldolase and transketolase
Flux through the PPP is controlled by rate of glucose-6-phosphate dehydrogenase reaction
Glycogen breakdown
Glycogen debranching enzyme removes glycogen's branches
makes additional glucose residues accessible to glycogen phosphorylase
glycosyltransferase
Transfers trisaccharide unit from limit branch of glycogen to nonreducing end of other branch.
separate active sites for the transferase adn glucosidase reactions
Phosphoglucomutase
Converts G1P to G6P
Phosphoryl group transferred from active phosphoenzyme to G1P, forming G1,6P. Rephosphorylates to G6P
Reversible
G6P generates glucose in liver
Can continue on glycolytic pathway or PPP
Glycogen phosphorylase catalyses phosphorolysis
Yields glucose-1-phosphate (G1P)
Glycogen+Pi <->glycogen + G1P
Phosphorylase degrades Glycogen to G1P
Catalyzes rate-controlling step
Inhibitors
ATP, G6P, Glucose
Activators
AMP
Binds cofactor PLP, needs it for activity
Crevice connects glycogen storage site to active site
Accomodates 4 or 5 sugar residues
Phosphorylase undergoes conformational changes
R State
Accessible catylatic site
Glycogen synthesis
Must occur through separate pathway to breakdown
UDP-glucose pyrophosphorylase
Activated compound which donates glucosyl units to glycogen chain
Glycogen synthase extends glycogen chains
UDPG transferred to C4-OH group to form glycosidic bond
UDPG+glycogen(n residues -> UDP + glycogen(n+1 residues)
UTP consumption energetically equivalent to ATP consumption
One molecule UTP cleaved to UDP for each glucose residue incorporated into glycogen.
Glycogen branching enzyme tranfers seven-residue glycogen segments
(1,4->1,6)-transglycosylase
Control of Glycogen metabolism
G phosphorylase and synthase under allosteric control
Flux is possible when an enzyme far from equilibrium is opposed by separately controlled enzyme
by ATP, G6P and AMP
Covalent modification of these provides a more sophisticated control system
Must be controlled according to cellular needs
Phos and synth undergo control by covalent modification
through enzyme-catalyzed phosphorylation and dephosphorylation
Enzymatically interconvertible enzyme systems respond to greater number of effectors than allosteric systems
Phosphorylation
Phosphorylase kinase
Phos. ser14 of glycogen phosphorylase b
Activated by Ca2+
Rate of glycogen breakdown is linked to rate of muscle contraction
Muscle transaction also triggered by transient increase in cytosolic Ca2+
Protein kinase A
Activates phosphorylase kinase
Activated by cAMP
cAMP controls fraction of enzyme in its phosphorylated form by increasing rate of phosphorylation and decreasing dephosphorylation
Phosphoprotein phosphatase-1 (PP1)
dephosphorylates and deactivates phosphorylase a and phosphorylase kinase
Inhibited by phosphoprotein inhibitor-1
activated by PKA and deactivated by PP1
Balance between phosphorylation and hydrolytic dephosphorylation
Bound to GL- glycogen sub-binding unit
Glycogen synthase is elaborately regulated
Inactivated by phosphorylase kinase
Subject to hormonal control
Polypeptide hormones insulin and glucagon in oppositon
Both synthesised in pancreas in response to concentration of glucose in the blood.
Muscles
Control by insulin and epinephrine and norepinephrine
Affect metabolism in target tissues by stimulating covalent modification (phosphorylation) of regulatory enzymes
Bind to transmembrane receptors on the surface of cells.
Different cell types have different complements of receptors and respond to different hormones
Involves the release of second messengers
Gluconeogenesis
synthesis of glucose from non-carbohydrate precursors (pyruvvate to glucose)
Liver and kidney synthesise it from lactate, pyruvate and amino acids
Must all be converted to oxaloacetate, except for leucine and lysine
A. Pyruvate converted to phosphoenolpyruvate (PEP) in two steps
Requires free energy input
Conversion of pyruvate to oxaloacetate
Its ezergonic decarboxylation provides the free energy needed for PEP synthesis
Needs two enzymes
Pyruvate carboxylase
Catalyzes the ATP-driven formation of oxaloacetate from pyruvate and HCO-3
Has a biotin prosthetic group - essential human nutrient
Two phases
Cleavage of ATP to ADP
transfer from carboxybiotin to pyruvate to form oxoa...
PEP carboxykinase(PEPCK)
converts oxoa.. to PEP in reaction using GTP as a phosphoryl group donor
Gluconeogenesis requires metabolite transport between mitochondria and cytosol
Oxaloacetate has to be converted to aspartate or malate first
B. Hydrolytic reactions bypass irreversible Glycolytic reactions.
Must be bypassed by different gluconeogenic enzymes
FBP hydrolyzed by FBPase, leading to F6P
Cost of converting two pryuvate molecules to glucose molecule is 6 ATP: two each at each catalyzed step
C. Gluconeogenesis and glycolysis are independently regulated
Fructose-2,6-Bisphosphate
activates phosphofructokinase
Inhibits fructose-1,6-Bisphosphatase
Other allosteric effectors influence gluconeogenic flux
Acetyl CoA activates pyruvate carboxylasse
Pyruvate kinase inhibited by alanine
Hexokinase also controlled
PEPCK not controlled
gluconeogenesis
Pyruvate to malate
Pyruvate carboxylase
In mitochondria
Oxaloacetate
malate dehydrogenase
Reversible
NADH --> NAD+
Malate can move through mitochondria to cytosol
Reconverts to oxaloacetate
Then processed by PEP carboxykinase
Precursors
Lactate
Anaerobic metabolism
Cori Cycle
Amino acids
TCA cycle
Oxaloacetate
Glycerol
Breakdown of triglyceride catabolism
3 enzymes
Hexokinase
PFK-1
Pyruvate kinase