Fluxion v5.6.1

Fluxion

What's New

• The Reaction Flow Map has been rebuilt from the ground up. Every pathway diagram now arranges itself automatically instead of relying on fixed positions: each box grows to fit its label, the connecting arrows route cleanly through the gaps between boxes, and every section resizes to hold whatever it contains. The maps are far easier to read and hold up at any window or monitor size.
• The citric acid cycle is now drawn as a true loop, with each enzyme sitting between the two metabolites it connects. Glycolysis snakes across two rows so the whole pathway stays legible, and the Complete Overview lays out every metabolite and reaction in the model at once without a single box or label colliding.

Improvements

• The flow map fits and scales to any monitor or window size. "Fit View" always frames the entire diagram with its title in view, the mouse wheel zooms in and out around the pointer, and dragging pans across the larger maps.
• Long enzyme names are wrapped onto short lines, and every reaction rate and concentration stays fully readable inside its box.

Bug Fixes

• Flow-map arrows no longer cut through boxes; they begin and end cleanly at the box edges.
• Box labels and reaction values no longer overflow or get clipped by their boxes.
• Pathway sections no longer overlap one another or spill their contents past their borders.
• The Reaction Flow Map now opens at a sensible zoom instead of fully zoomed out.

Known Issues

• The respiratory slip that oxidises the resting matrix is modelled as a single lumped pathway, which leaves a few small artefacts: the membrane potential dips slightly at the very lowest workloads before falling as work increases, the resting cell takes a little longer to settle to a perfectly steady state, and oxidative metabolism runs a touch less efficient than the textbook oxygen-to-ATP ratio. Smoothing these needs a deeper rework that lets the chain's coupling vary continuously with the driving force, which is planned.
• During prolonged oxygen-free work the modelled cell drifts slightly alkaline instead of acidifying, because exported lactate carries its acid out to the blood pool, which is not modelled as buffered.

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SHA-256 checksum

991c1a219ed1646ec8f31e58888498efe053daabe37da28424d6f15621374f11

Fluxion v5.6.0

Fluxion

What's New

• The Reaction Flow Map has been rebuilt from the ground up. Every pathway diagram now arranges itself automatically instead of relying on fixed positions: each box grows to fit its label, the connecting arrows route cleanly through the gaps between boxes, and every section resizes to hold whatever it contains. The maps are far easier to read and hold up at any window or monitor size.
• The citric acid cycle is now drawn as a true loop, with each enzyme sitting between the two metabolites it connects. Glycolysis snakes across two rows so the whole pathway stays legible, and the Complete Overview lays out every metabolite and reaction in the model at once without a single box or label colliding.

Improvements

• The flow map fits and scales to any monitor or window size. "Fit View" always frames the entire diagram with its title in view, the mouse wheel zooms in and out around the pointer, and dragging pans across the larger maps.
• Long enzyme names are wrapped onto short lines, and every reaction rate and concentration stays fully readable inside its box.

Bug Fixes

• Flow-map arrows no longer cut through boxes; they begin and end cleanly at the box edges.
• Box labels and reaction values no longer overflow or get clipped by their boxes.
• Pathway sections no longer overlap one another or spill their contents past their borders.

Known Issues

• The respiratory slip that oxidises the resting matrix is modelled as a single lumped pathway, which leaves a few small artefacts: the membrane potential dips slightly at the very lowest workloads before falling as work increases, the resting cell takes a little longer to settle to a perfectly steady state, and oxidative metabolism runs a touch less efficient than the textbook oxygen-to-ATP ratio. Smoothing these needs a deeper rework that lets the chain's coupling vary continuously with the driving force, which is planned.
• During prolonged oxygen-free work the modelled cell drifts slightly alkaline instead of acidifying, because exported lactate carries its acid out to the blood pool, which is not modelled as buffered.

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SHA-256 checksum

8945539a6f6d9f23259573a15f55f979d752bc0b86f3ef66272f4430948d0ee3

Fluxion v5.5.9

Fluxion

What's New

• Crash reporting system integrated to monitor and report application crashes in real-time.
• Realistic mitochondrial membrane potential and matrix pH. The inner-membrane potential now sits in the physiological 150-190 mV range and falls as the cell works harder, rather than reading around 230 mV and climbing under load, and the matrix correctly runs about half a pH unit more alkaline than its surroundings. The guided Oxygen Supply exercise is far more accurate as a result.
• A working aerobic-to-anaerobic switch, driven by a new glycerol-3-phosphate shuttle. As oxygen is withdrawn the cell now spends phosphocreatine first, then floods with lactate as anaerobic glycolysis takes over and defends ATP -- the exact sequence the Oxygen Supply exercise is meant to teach, which the model previously could not sustain.

Improvements

• ROS balance and buffer split
• Matrix malate and the other citric-acid-cycle intermediates now hold at physiological levels during sustained exercise instead of slowly accumulating over several minutes.
• A realistic resting cell. The default resting simulation now runs at a physiological resting metabolic rate, with the membrane potential settling near 180 mV, instead of the previous near-zero "idling" state that pushed the potential unnaturally high and left the resting readouts unphysiological.
• Stable resting phosphate. Cytosolic free phosphate now holds a steady, realistic resting level of about 1 mM and rises during exercise as phosphocreatine is spent, instead of being stripped toward zero. A phosphate-homeostasis process now keeps it in balance, standing in for the cell's phosphate transport and regulation.
• A realistically oxidised resting matrix. At rest the mitochondrial matrix now holds a physiological oxidised balance (NAD+/NADH around 5) instead of reading almost fully reduced. Real mitochondria never sit exactly at their maximum driving force, even at rest; the model now captures that with a small "respiratory slip" — a finite-coupling pathway that carries a few electrons to oxygen while pumping fewer charges — so the chain runs just below its ceiling and both the matrix balance and the membrane potential land in their measured ranges.

Bug Fixes

• Long simulations of hard exercise or low oxygen no longer collapse to zero ATP after a few minutes; they now stay stable for a full simulated hour.

Known Issues

• The respiratory slip that oxidises the resting matrix is modelled as a single lumped pathway, which leaves a few small artefacts: the membrane potential dips slightly at the very lowest workloads before falling as work increases, the resting cell takes a little longer to settle to a perfectly steady state, and oxidative metabolism runs a touch less efficient than the textbook oxygen-to-ATP ratio. Smoothing these needs a deeper rework that lets the chain's coupling vary continuously with the driving force, which is planned.
• During prolonged oxygen-free work the modelled cell drifts slightly alkaline instead of acidifying, because exported lactate carries its acid out to the blood pool, which is not modelled as buffered.

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SHA-256 checksum

f9a881b8e980003921666b232f21953100e196fb206c3f5cb0d8e4cb9bfaafc9

Fluxion v5.5.6

Fluxion 5.5.6

What's New

• Crash reporting system integrated to monitor and report application crashes in real-time.
• Realistic mitochondrial membrane potential and matrix pH. The inner-membrane potential now sits in the physiological 150-190 mV range and falls as the cell works harder, rather than reading around 230 mV and climbing under load, and the matrix correctly runs about half a pH unit more alkaline than its surroundings. The guided Oxygen Supply exercise is far more accurate as a result.
• A working aerobic-to-anaerobic switch, driven by a new glycerol-3-phosphate shuttle. As oxygen is withdrawn the cell now spends phosphocreatine first, then floods with lactate as anaerobic glycolysis takes over and defends ATP -- the exact sequence the Oxygen Supply exercise is meant to teach, which the model previously could not sustain.

Improvements

• ROS balance and buffer split
• Matrix malate and the other citric-acid-cycle intermediates now hold at physiological levels during sustained exercise instead of slowly accumulating over several minutes.

Bug Fixes

• Long simulations of hard exercise or low oxygen no longer collapse to zero ATP after a few minutes; they now stay stable for a full simulated hour.

Known Issues

• Resting free phosphate reads low, from how the model divides phosphate between free phosphate, ATP, and phosphocreatine at rest.
• The mitochondrial matrix is somewhat more chemically reduced than measured (matrix NAD+/NADH sits below the textbook value).
• During prolonged oxygen-free work the modelled cell drifts slightly alkaline instead of acidifying, because exported lactate carries its acid out to the blood pool, which is not modelled as buffered.

---

SHA-256 checksum

70617d5e163a71ba43598bc39d5f7fb47e172d936d26c126743f1b919c3565ee

Fluxion v5.5.5

Fluxion 5.5.5

What's New

• Crash reporting system integrated to monitor and report application crashes in real-time.

Improvements

• ROS balance and buffer split

Bug Fixes

Known Issues

• The membrane potential reads high, around 200 mV against a textbook 150-180. The total driving force across the membrane is correct, but the model cannot yet split it properly between the electrical and pH components, so too much of it shows up as voltage. Mitochondrial and cytosolic NAD+/NADH ratios are lower than measured values for the same reason.

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SHA-256 checksum

3f396fd3c85b46a7a60558d940453f64de110ab56e364508fcc0b66b5e8df79c

Fluxion v5.5.4

Fluxion 5.5.4

What's New

• Crash reporting system integrated to monitor and report application crashes in real-time.

Improvements

Bug Fixes

Known Issues

• T

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SHA-256 checksum

a6ed8222c9c25bab02fe0ff9802ff02f12a850effa35ac5706d623fb83cc049b

Fluxion v5.5.2

Fluxion 5.5.2

What's New

• Glycogen system added to the model. This system is responsible for glycogen synthesis and breakdown. It is a key component of energy storage and release in cells.
• The malate-aspartate shuttle is now modelled properly, as the six reactions it actually is, instead of a single placeholder. Its aspartate/glutamate carrier moves net charge, which is what makes the shuttle run one way in a respiring cell.
• Compartments now have realistic volumes. The intermembrane space is a thin shell rather than a space the size of the cytosol, so material moved into it no longer disappears from the cell's working pools.
• The mitochondrial membrane potential is now a real voltage, shown in millivolts, calculated from charge separation across the membrane. Every reaction that moves charge responds to it.

Improvements

• Re-evaluation of literature values for many reactions. Largest fix being malate dehydrogenase.
• Reversible reactions now hold their equilibrium constants at every concentration. Previously they only did so while metabolites stayed well below their Km values, and drifted badly above that: triose phosphate isomerase sat 96x away from its correct equilibrium, which trapped most of glycolysis' carbon in DHAP and stalled the pathway.
• The electron transport chain has been rebuilt on published midpoint potentials, with the correct proton and charge stoichiometry for each complex.
• ATP synthase is a single reaction driven by the protonmotive force, replacing a two-step rotor-and-catalysis pair joined by an invented intermediate.
• The adenine nucleotide translocase, phosphate carrier and pyruvate carrier now respond to the membrane potential and pH gradient instead of having those effects written in as fixed constants.
• Lactate leaves the cell with its proton, as it does through the real transporter. Without this the cell acidified without limit under load.
• Phosphofructokinase is now inhibited by falling pH, the feedback that stops glycolysis outrunning its own downstream capacity during hard work.
• Enolase and adenylate kinase equilibrium constants corrected. Enolase was carrying fumarase's value.
• Resting concentrations updated to measured muscle values, including ATP, free ADP and AMP, and the citric acid cycle intermediates, which previously all started at zero.
• Guided exercise workloads rebalanced so the aerobic, hypoxic and anaerobic conditions separate clearly across phosphocreatine, lactate, membrane potential and ATP.
• Simulations run roughly twice as fast, after switching to a solver better suited to the model. The change was made to fix the crash noted below, and the speedup came with it.

Bug Fixes

• Reduced lag spike when using timed velocity changes.
• Creatine kinase and pyruvate kinase could consume protons the cell did not have, because neither slowed down as free protons ran out.
• Several reactions that produce NADH were not producing the proton that comes with it, and ATP synthase was not consuming the one that ATP synthesis takes up. Both left the model quietly creating or destroying acid.
• The lactate transporter's reverse velocity was ten thousand times too high, which drove blood lactate slightly negative early in a run.
• Restoring oxygen to a cell that had been running anaerobically could stop the simulation partway through, either with a "math domain error" or with the solver giving up. Recovery from anaerobic conditions is a demanding moment to calculate — the electron transport chain restarts against a collapsed membrane potential and everything moves at once — and both the arithmetic and the solver now handle it.

Known Issues

• The membrane potential reads high, around 200 mV against a textbook 150-180. The total driving force across the membrane is correct, but the model cannot yet split it properly between the electrical and pH components, so too much of it shows up as voltage. Mitochondrial and cytosolic NAD+/NADH ratios are lower than measured values for the same reason.

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SHA-256 checksum

d069afbe153c73162b501b477b121e0722647b03af9ab9822575e3b985aad1cb

Fluxion v5.5.1

Fluxion 5.5.1

What's New

• Glycogen system added to the model. This system is responsible for glycogen synthesis and breakdown. It is a key component of energy storage and release in cells.
• The malate-aspartate shuttle is now modelled properly, as the six reactions it actually is, instead of a single placeholder. Its aspartate/glutamate carrier moves net charge, which is what makes the shuttle run one way in a respiring cell.
• Compartments now have realistic volumes. The intermembrane space is a thin shell rather than a space the size of the cytosol, so material moved into it no longer disappears from the cell's working pools.
• The mitochondrial membrane potential is now a real voltage, shown in millivolts, calculated from charge separation across the membrane. Every reaction that moves charge responds to it.

Improvements

• Re-evaluation of literature values for many reactions. Largest fix being malate dehydrogenase.
• Reversible reactions now hold their equilibrium constants at every concentration. Previously they only did so while metabolites stayed well below their Km values, and drifted badly above that: triose phosphate isomerase sat 96x away from its correct equilibrium, which trapped most of glycolysis' carbon in DHAP and stalled the pathway.
• The electron transport chain has been rebuilt on published midpoint potentials, with the correct proton and charge stoichiometry for each complex.
• ATP synthase is a single reaction driven by the protonmotive force, replacing a two-step rotor-and-catalysis pair joined by an invented intermediate.
• The adenine nucleotide translocase, phosphate carrier and pyruvate carrier now respond to the membrane potential and pH gradient instead of having those effects written in as fixed constants.
• Lactate leaves the cell with its proton, as it does through the real transporter. Without this the cell acidified without limit under load.
• Phosphofructokinase is now inhibited by falling pH, the feedback that stops glycolysis outrunning its own downstream capacity during hard work.
• Enolase and adenylate kinase equilibrium constants corrected. Enolase was carrying fumarase's value.
• Resting concentrations updated to measured muscle values, including ATP, free ADP and AMP, and the citric acid cycle intermediates, which previously all started at zero.
• Guided exercise workloads rebalanced so the aerobic, hypoxic and anaerobic conditions separate clearly across phosphocreatine, lactate, membrane potential and ATP.
• Simulations run roughly twice as fast, after switching to a solver better suited to the model. The change was made to fix the crash noted below, and the speedup came with it.

Bug Fixes

• Reduced lag spike when using timed velocity changes.
• Creatine kinase and pyruvate kinase could consume protons the cell did not have, because neither slowed down as free protons ran out.
• Several reactions that produce NADH were not producing the proton that comes with it, and ATP synthase was not consuming the one that ATP synthesis takes up. Both left the model quietly creating or destroying acid.
• The lactate transporter's reverse velocity was ten thousand times too high, which drove blood lactate slightly negative early in a run.
• Restoring oxygen to a cell that had been running anaerobically could stop the simulation partway through, either with a "math domain error" or with the solver giving up. Recovery from anaerobic conditions is a demanding moment to calculate — the electron transport chain restarts against a collapsed membrane potential and everything moves at once — and both the arithmetic and the solver now handle it.

Known Issues

• The membrane potential reads high, around 200 mV against a textbook 150-180. The total driving force across the membrane is correct, but the model cannot yet split it properly between the electrical and pH components, so too much of it shows up as voltage. Mitochondrial and cytosolic NAD+/NADH ratios are lower than measured values for the same reason.

---

SHA-256 checksum

9811d39af2da6b270a16c862ea6bd43d9341342ea8a03e60edd8aa68043b0642

Fluxion v5.4.9

Fluxion 5.4.9

What's New

• Glycogen system added to the model. This system is responsible for glycogen synthesis and breakdown. It is a key component of energy storage and release in cells.
• The malate-aspartate shuttle is now modelled properly, as the six reactions it actually is, instead of a single placeholder. Its aspartate/glutamate carrier moves net charge, which is what makes the shuttle run one way in a respiring cell.
• Compartments now have realistic volumes. The intermembrane space is a thin shell rather than a space the size of the cytosol, so material moved into it no longer disappears from the cell's working pools.
• The mitochondrial membrane potential is now a real voltage, shown in millivolts, calculated from charge separation across the membrane. Every reaction that moves charge responds to it.

Improvements

• Re-evaluation of literature values for many reactions. Largest fix being malate dehydrogenase.
• Reversible reactions now hold their equilibrium constants at every concentration. Previously they only did so while metabolites stayed well below their Km values, and drifted badly above that: triose phosphate isomerase sat 96x away from its correct equilibrium, which trapped most of glycolysis' carbon in DHAP and stalled the pathway.
• The electron transport chain has been rebuilt on published midpoint potentials, with the correct proton and charge stoichiometry for each complex.
• ATP synthase is a single reaction driven by the protonmotive force, replacing a two-step rotor-and-catalysis pair joined by an invented intermediate.
• The adenine nucleotide translocase, phosphate carrier and pyruvate carrier now respond to the membrane potential and pH gradient instead of having those effects written in as fixed constants.
• Lactate leaves the cell with its proton, as it does through the real transporter. Without this the cell acidified without limit under load.
• Phosphofructokinase is now inhibited by falling pH, the feedback that stops glycolysis outrunning its own downstream capacity during hard work.
• Enolase and adenylate kinase equilibrium constants corrected. Enolase was carrying fumarase's value.
• Resting concentrations updated to measured muscle values, including ATP, free ADP and AMP, and the citric acid cycle intermediates, which previously all started at zero.
• Guided exercise workloads rebalanced so the aerobic, hypoxic and anaerobic conditions separate clearly across phosphocreatine, lactate, membrane potential and ATP.
• Simulations run roughly twice as fast, after switching to a solver better suited to the model. The change was made to fix the crash noted below, and the speedup came with it.

Bug Fixes

• Reduced lag spike when using timed velocity changes.
• Creatine kinase and pyruvate kinase could consume protons the cell did not have, because neither slowed down as free protons ran out.
• Several reactions that produce NADH were not producing the proton that comes with it, and ATP synthase was not consuming the one that ATP synthesis takes up. Both left the model quietly creating or destroying acid.
• The lactate transporter's reverse velocity was ten thousand times too high, which drove blood lactate slightly negative early in a run.
• Restoring oxygen to a cell that had been running anaerobically could stop the simulation partway through, either with a "math domain error" or with the solver giving up. Recovery from anaerobic conditions is a demanding moment to calculate — the electron transport chain restarts against a collapsed membrane potential and everything moves at once — and both the arithmetic and the solver now handle it.

Known Issues

• The membrane potential reads high, around 200 mV against a textbook 150-180. The total driving force across the membrane is correct, but the model cannot yet split it properly between the electrical and pH components, so too much of it shows up as voltage. Mitochondrial and cytosolic NAD+/NADH ratios are lower than measured values for the same reason.

---

SHA-256 checksum

f8ba49e0466c1414e2b60a144268f58c5a3a1ea29fac158cc897a03b96d018e8

Fluxion v5.4.8

Fluxion 5.4.8

What's New

• Glycogen system added to the model. This system is responsible for glycogen synthesis and breakdown. It is a key component of energy storage and release in cells.
• The malate-aspartate shuttle is now modelled properly, as the six reactions it actually is, instead of a single placeholder. Its aspartate/glutamate carrier moves net charge, which is what makes the shuttle run one way in a respiring cell.
• Compartments now have realistic volumes. The intermembrane space is a thin shell rather than a space the size of the cytosol, so material moved into it no longer disappears from the cell's working pools.
• The mitochondrial membrane potential is now a real voltage, shown in millivolts, calculated from charge separation across the membrane. Every reaction that moves charge responds to it.

Improvements

• Re-evaluation of literature values for many reactions. Largest fix being malate dehydrogenase.
• Reversible reactions now hold their equilibrium constants at every concentration. Previously they only did so while metabolites stayed well below their Km values, and drifted badly above that: triose phosphate isomerase sat 96x away from its correct equilibrium, which trapped most of glycolysis' carbon in DHAP and stalled the pathway.
• The electron transport chain has been rebuilt on published midpoint potentials, with the correct proton and charge stoichiometry for each complex.
• ATP synthase is a single reaction driven by the protonmotive force, replacing a two-step rotor-and-catalysis pair joined by an invented intermediate.
• The adenine nucleotide translocase, phosphate carrier and pyruvate carrier now respond to the membrane potential and pH gradient instead of having those effects written in as fixed constants.
• Lactate leaves the cell with its proton, as it does through the real transporter. Without this the cell acidified without limit under load.
• Phosphofructokinase is now inhibited by falling pH, the feedback that stops glycolysis outrunning its own downstream capacity during hard work.
• Enolase and adenylate kinase equilibrium constants corrected. Enolase was carrying fumarase's value.
• Resting concentrations updated to measured muscle values, including ATP, free ADP and AMP, and the citric acid cycle intermediates, which previously all started at zero.
• Guided exercise workloads rebalanced so the aerobic, hypoxic and anaerobic conditions separate clearly across phosphocreatine, lactate, membrane potential and ATP.
• Simulations run roughly twice as fast, after switching to a solver better suited to the model. The change was made to fix the crash noted below, and the speedup came with it.

Bug Fixes

• Reduced lag spike when using timed velocity changes.
• Creatine kinase and pyruvate kinase could consume protons the cell did not have, because neither slowed down as free protons ran out.
• Several reactions that produce NADH were not producing the proton that comes with it, and ATP synthase was not consuming the one that ATP synthesis takes up. Both left the model quietly creating or destroying acid.
• The lactate transporter's reverse velocity was ten thousand times too high, which drove blood lactate slightly negative early in a run.
• Restoring oxygen to a cell that had been running anaerobically could stop the simulation partway through, either with a "math domain error" or with the solver giving up. Recovery from anaerobic conditions is a demanding moment to calculate — the electron transport chain restarts against a collapsed membrane potential and everything moves at once — and both the arithmetic and the solver now handle it.

Known Issues

• The membrane potential reads high, around 200 mV against a textbook 150-180. The total driving force across the membrane is correct, but the model cannot yet split it properly between the electrical and pH components, so too much of it shows up as voltage. Mitochondrial and cytosolic NAD+/NADH ratios are lower than measured values for the same reason.

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SHA-256 checksum

5cff8fdc5b975b379bbd98462956a93180bccb6c8d5b9a54e5b490b8fd8909b8