Lectures 19/20: Carbohydrate Metabolism Flashcards
Negative deltaG
Keq greater than 1
More products than substrates in equilibrium
Exergonic reaction towards products
Favourable reaction towards products
Positive deltaG
Keq is less than 1
More substrate than products in equilibrium
Endergonic reaction towards products
Non-favourable reaction towards products
GLUT
Specific glucose transporters that take glucose inside cell
Several forms based on tissue and cell type
Transporters facilitate bidirectional transport of glucose (in and out), always from higher to lower concentration of glucose
Does not transport phosphorylated glucose
Glucose uptake
By GLUT
Reversible, deltaG nearly 0
Direction of glucose transport depends on substrate/product levels
Phosphorylation removes glucose from equilibrium
Entry of glucose depends on GLUT transporters and the activity of hexokinase
Pyruvate
Glucose is converted to 2 pyruvate, 2 3-carbon molecules
Glycolysis
Oxidation of glucose to pyruvate
Net yield of 2 ATP
2 ATP are invested, and 4 are made
Electron carriers are reduced
Gluconeogenesis
Reverse conversion of pyruvate to glucose
Reversible glycolysis reactions use the same enzyme
Irreversible glycolysis reactions use different enzymes
Phase 1 of glycolysis
Energy investment
Steps 1-5
Phosphorylation of glucose and conversion of 2 molecules of glyceraldehyde-3-phosphate
Two ATP are used
Phase 2 of glycolysis
ATP production phase
Steps 6-10
Conversion of glyceraldehyde-3-phosphate to pyruvate and coupled formation of 4 ATP
Reduction of 2NAD+ to 2NADH
Step 1 of glycolysis
Hexokinase phosphorylates glucose to glucose-6-phosphate
1 ATP used
Irreversible
Step 2 of glycolysis
Isomerization of glucose 6-phosphate to Fructose-6-phosphate
Catalyzed by phosphoglucose isomerase (PGI)
Step 3 of glycolysis
Phosphorylation of Fructose-6-phosphate to Fructose-1,5-bisphosphate
1 ATP used
Irreversible
Catalyzed by phosphofructokinase
Phosphofructokinase-1
Phosphorylates fructose-6-phosphate to give fructose-1,6-phosphate (more symmetrical)
Allosterically regulated by fructose-2,6-BP
Addition of ATP reduces PFK1 and more F-2,6-BP needed to activate
Addition of AMP increases activity
Steps 4 and 5 of glycolysis
Cleavage of carbon backbone to dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phsohate (GAP)
Isomermization of DHAP and GAP by triose phosphate isomerase
Triose phosphate isomerase
Isomerizes GAP and DHAP (become readily interchangeable, allows glycolysis to proceed using the same enzymes for each)
Step 6 of glycolysis
Oxidation and addition of inorganic phosphate to GAP by glyceraldehyde-3-phosphate dehydrogenase
NAD is needed
1,3-biphosphateglycerate (1,3-BPG) and NADH are produced
Glyceraldehyde-3-phosphate dehyrogenase
Oxidized and adds phosphate to GAP
Generates 1,3-bisphosphoglycerate and NADH
Step 7 of glycolysis
Dephosphorylation and first generation of ATP from 1,3-BPG by phosphoglycerate kinase to generate 3-phosphoglycerate
Direction and flux influenced by ATP
Step 8 of glycolysis
Phosphoglycerate mutate moves phosphate from 3 to 2 position on 3-phosphoglycerate
Phosphoglycerate kinase
Generates 3-phosphoglycerate from 1,3-BPG
Generates 1 ATP (but occurs twice per glucose molecule)
Step 9 of glycolysis
Dehydration of 2-phosphoglycerate to phosphoenolpyruvate by enolase
Generates H2O
Steps 10 of glycolysis
Formation of pyruvate and generation of second ATP
Irreversible
Catalyzed by pyruvate kinase
Pyruvate kinase
Catalyzes the generation of ATP and pyruvate from phosphoenolpyruvate
Happens twice per glucose molecule to give 2 ATP total
Pyruvate
Can take many different routes
Aerobic: mitochondrial conversion of pyruvate to acetyl-CoA and oxidation in the TCA cycle
Anaerobic: cytosolic regeneration of NAD+
Alcoholic fermentation
Yeast regenerates NAD+ by making ethanol
Catalyzed by pyruvate decarboxylase and alcohol dehydrogenase
Lactic fermentation
Pyruvate and NADH fermentation by lactase dehydrogenase gives lactic acid and NAD+
Lactate is secreted from the cell and acidifies the environment
Anaerobic glycolysis
Glycolysis followed by conversion of pyruvate to lactate
Generates 2ATP
Full oxidation of pyruvate to CO2 requires oxygen and mitochondria
Gluconeogenesis
Generation of glucose from various substrates: pyruvate, lactate, glycerol, most amino acids, all citric acid cycle intermediates
Not exact reverse of glycolysis
Unique gluconeogenic enzymes: glucose phosphatase, fructobisphosphatase, phosphoenolpyruvate carboxykinase, pyruvate carboxylase
Glucose phosphatase
Reverse of hexokinase
Glucose phosphorylation by hexokinase is irreversible and has high -deltaG
If both were coupled, it would have a net cost of 1ATP
Oxaloacetate
For last step reversal (first step of gluconeogenesis from pyruvate) pyruvate carboxylase catalyses oxaloacetate formation from pyruvate
Requires ATP
Pyruvate carboxylase
Converts pyruvate to oxaloacetate, using 1ATP
Phosphoenolpyruvate carboxykinase
Converts oxaloacetate to phosphoenolpyruvate
Uses 1GTP
Phosphofructokinase 2
Phosphorylates fructose-6P at 2 carbon to generate Fructose-2,6-BP
Fructose-2,6-bisphosphate
Most potent activator of phosphofructokinase in mammals
Allosteric activator of PFK1
Inhibits fructobisphosphatase: inhibits gluconeogenesis
Product inhibition
Product of enzyme inhibits enzyme
Does not change reaction, but changes rates
Covalent modification
Usually catalyzed by other enzyme
Usually phosphorylations and dephosphorylations through kinases and phosphatases
Allosteric control
Feedback, feedforward within one pathway
Metabolites from other pathways regulate connected pathways
Feedforward interaction is more rare
Feedback inhibition
Prevents overproduction of product
Feedforward activation
Ensures completion of the pathway
Pentose pathway
Provides different intermediates
Intermediates of pathway can be used for synthesis of nucleotides
Highly adaptable to needs of cell
Feeds into glycolysis
Can make 2 fructose-6-P and glyceraldehyde-3-phoshate (GAP)
Glycogen
Synthesized from monomer of glucose-1-phosphate - isomerized from glucose-6-phoshate
UTP
Bonds with glucose-1-P to give glucose-UDP and 1P
Glucose added to glycogen polymer though glycogen synthase and release of UDP
Glycogen break down
Linear chaines broken down via phosphorolysis
Branched chains broken down by hydrolysis
Fructose metabolism
Usually phosphorylated by hexokinase to fructose-6-phosphate
Does not occur in liver
No feedback mechanism
If liver gets overwhelmed by byproducts, they can enter fat synthesis
Liver transports can only transport a fraction of fructose
Fructose metabolism in liver
Glucoinase cannot metabolize fructose
Converted to fructose-1-phosphate by fructokinase
Fructose-1-Phosphate
converted to glyceraldehyde-3-phosphate which enters glycolysis after main regulatory step
