Energetics of life Flashcards
The three common features of life
Proton gradients, reducing power (FAD/FADH, NAD+/NADH, fe2-/fe3+, iron sulphur compounds), ATP
- Proton gradients
Essentially universal for metabolism by all living organisms: an energy coupling mechanism that uses energy stored in the form of an H+ gradient across a membrane to drive cellular work.
- Reducing power: oxidation + reduction
Oxidation and Reduction:
Oxidation refers to the loss of electrons. In the diagram, Compound A (shown on the top) is the electron donor, which means it loses electrons and becomes oxidized (represented by the movement of the electrons away from A).
Reduction refers to the gain of electrons. Compound B (shown on the bottom) is the electron acceptor, which gains the electrons lost by A and becomes reduced.
Electron Donor and Reducing Agent:
Compound A, as the electron donor, acts as a reducing agent. A reducing agent donates electrons to another compound and is itself oxidized in the process.
Electron Acceptor and Oxidizing Agent:
Compound B, as the electron acceptor, acts as an oxidizing agent. An oxidizing agent accepts electrons from another compound and is itself reduced in the process.
- Concept of reducing power generated from food and its role in cellular metabolism
Breakdown:
Food as a Source of Reducing Power:
The left side of the image shows food consumption (with an amusing image of someone eating) as the source of energy. When we consume food, metabolic processes convert nutrients into energy through biochemical pathways like glycolysis, the citric acid cycle, and oxidative phosphorylation.
Electron Carriers:
The key electron carriers involved in metabolism are NAD+, NADP+, and FAD. These molecules accept electrons (becoming reduced) and store energy:
NAD+ becomes NADH.
NADP+ becomes NADPH.
FAD becomes FADH2.
In the image, the “flat and worn out” bunny on the top represents the oxidized (electron-deficient) forms of these cofactors (NAD+, NADP+, FAD), which are unable to provide energy.
Reduction and Energy Storage:
As these cofactors gain electrons (become reduced), they store energy in the form of reducing power, turning into NADH, NADPH, and FADH2. The fully charged, energetic bunny represents these reduced forms that now contain usable energy for the cell.
Role in Cellular Metabolism:
The reduced cofactors (NADH, NADPH, FADH2) carry electrons to drive important metabolic processes. They are essential for producing energy (via oxidative phosphorylation) and for biosynthetic reactions such as fat synthesis. This is indicated by the arrow leading to the right, which shows how reduced cofactors contribute to cellular energy and biosynthesis.
Cellular Energy and Biosynthesis:
The right side of the image highlights that the energy stored in NADH, NADPH, and FADH2 drives cellular biosynthesis, including processes like fat synthesis, contributing to the cell’s overall energy requirements and anabolic processes.
Concept of electron carriers
NAD + & NADP + (Uncharged Form): On the left, we see the oxidized forms of NAD + and NADP + . These are the uncharged versions of the molecules. They have a positive charge on the nitrogen in their ring structure (indicated by the “+” in their names).
NADH & NADPH (Charged Form): On the right, NAD + and NADP + are shown in their reduced forms, NADH and NADPH. These reduced forms have accepted electrons (indicated by the yellow e − − symbols and the hydrogen atoms). Now, they are “charged” and can donate these electrons in metabolic reactions to provide energy.
FAD and FADH2 : The lower portion of the image explains the difference between FAD (the oxidized form, or uncharged form) and FADH2 (the reduced form, or charged form). FAD accepts two hydrogen atoms (along with electrons), becoming FADH 2 , which stores energy.
Reduction and Oxidation: The process of reduction (gaining electrons and becoming “charged”) and oxidation (losing electrons and becoming “uncharged”) is central to these molecules’ roles in metabolism. In the image, the transition from the “flat and worn out” bunny (oxidized form) to the “charged and energetic” bunny (reduced form) represents the cofactors’ role in cellular metabolism: when reduced, they store energy that can be used for various cellular processes.
Iron-sulfur clusters
Roles in reducing power (electron transfer)
- ATP action is like an energy currency: Roles of NAD(P)H and ATP in reducing CO2 and generating energy in chloroplasts (plant cells) and animal cells.
This image compares the roles of NAD(P)H and ATP in reducing CO2 and generating energy in chloroplasts (plant cells) and animal cells. The processes in both cases involve NADPH as a key electron carrier and ATP as an energy source for metabolic pathways.
Breakdown:
1. Chloroplast (Plant Cell):
In the chloroplast, which is responsible for photosynthesis in plants, light energy is used to drive reactions in the thylakoids.
Light reactions produce NADPH and ATP, which are crucial for the Calvin cycle.
The Calvin cycle uses these products to reduce CO2 into sugars (represented as [CH2
O]), which store energy in the form of carbohydrates.
In summary, NADPH provides reducing power (electrons), and ATP provides energy to fix carbon dioxide into organic molecules (sugars).
- Animal Cell:
In the animal cell, reducing power (NADPH) and ATP are similarly used but for different metabolic processes. Here, NADPH and ATP are crucial for fatty acid synthesis.
Energy-rich compounds from food are broken down through catabolic processes, generating carbon skeletons and energy.
NADPH and ATP are then used in fatty acid synthesis, an anabolic process where carbon atoms are assembled into fatty acids (key components of lipids).
Like in plants, NADPH provides reducing power, while ATP supplies energy to drive the synthesis.
ATP Structure and Comparison with NAD+
Image 1: ATP Structure and Comparison with NAD+
This image emphasizes the similarity between the structures of NAD+ (Nicotinamide Adenine Dinucleotide) and ATP (Adenosine Triphosphate). It points out that NAD+ is essentially composed of two AMP units (Adenosine Monophosphate) linked together, with one of the adenine bases replaced by a nicotinamide group.
Key Points:
NAD+:
NAD+ contains a nicotinamide group in place of one of the adenine groups found in AMP.
NAD+ consists of two nucleotides (adenosine and nicotinamide nucleotides) joined by their phosphate groups.
NAD+ plays a critical role in redox reactions, particularly as an electron carrier in cellular respiration.
AMP:
Adenosine monophosphate (AMP) is a component of both ATP and NAD+. It consists of an adenine base, a ribose sugar, and a phosphate group.
ATP:
ATP consists of the same adenine and ribose components as AMP but has three phosphate groups. It functions as the cell’s primary energy carrier, storing and transferring energy during metabolic reactions.
NAD+ and NADH Levels Indicate Energy Status of a Cell
Order of energy in ATP, ADP and AMP
Concept of LUCA, the Last Universal Common Ancestor
From LUCA, the three major domains of life evolved: Bacteria, Archaea, and later, Eukaryotes
Biochemical features of LUCA
Proton Gradients, Reducing Power, and ATP:
The diagram highlights that LUCA utilized proton gradients across its membrane to generate ATP using ATP synthase, a feature that modern cells also use for energy production.
Ferredoxin, a protein that carries electrons and plays a role in redox reactions, provided reducing power for LUCA’s metabolic processes.
The ATP was generated from ADP and inorganic phosphate using the proton gradient created across LUCA’s membrane.
Hydrogen as an Energy Source:
LUCA likely used H2 (hydrogen gas) as an energy source to reduce CO2 and drive metabolic reactions. This process suggests that LUCA was capable of chemosynthesis—using chemicals (in this case, H2) as an energy source rather than light, similar to modern organisms that live in extreme environments.
This reliance on hydrogen indicates that LUCA was likely an anaerobic organism, living in environments without oxygen, and used hydrogen to produce energy.
Strictly Anaerobic and Thermophilic:
The image indicates that LUCA’s genes point to a strictly anaerobic (oxygen-free) lifestyle, and LUCA was likely a thermophile, thriving in high-temperature environments such as hydrothermal vents.
This aligns with current theories that early life forms, including LUCA, might have originated in extreme environments like deep-sea hydrothermal vents, where heat and chemicals like hydrogen would have provided energy for life.
Genetic Code and Protein Machinery:
LUCA had established the basic framework of the genetic code and the protein synthesis machinery, including ribosomes, which allowed it to produce proteins and carry out life-sustaining biochemical reactions.
Cellular molecules such as lipids, DNA, and proteins were present, enabling LUCA to maintain a cellular structure, store genetic information, and perform metabolic functions.
Early Earth and the Origins of Life
The Earth is about 4.5 billion years old, and the environment was initially inhospitable, with meteorites bombarding the surface, no oxygen, and high CO2 levels.
The landscape was harsh, with no ozone layer to block UV radiation, making the surface brutal for life to develop.
Theories of Life’s Origins
Life likely didn’t evolve in calm, oxygen-rich environments but rather under harsh conditions.
Surface life was likely destroyed by UV radiation, so some theories propose that life formed underwater, particularly near hydrothermal vents.
There is evidence of ancient rocks in Western Australia and southern Africa, possibly remnants of a supercontinent, dating back to when oxygen was first being produced on Earth (~3.5 billion years ago).
Early organisms, possibly photosynthetic, were responsible for oxygen production, which led to the formation of banded iron formations once oxygen reached certain levels and precipitated iron from the oceans.
Hydrothermal Vents as a Crucial Location rich in H2, CO2, transition metals, sulfur
Black smokers (hydrothermal vents emitting hydrogen sulfide) and white smokers (alkaline hydrothermal vents) could have been crucial in the evolution of life.
Alkaline hydrothermal vents, such as those in the “Lost City” (Atlantic Ocean), are long-lived and more stable, making them ideal for the origin of life.
These vents have a significant proton gradient between the alkaline vent water and the more acidic ocean water (around a thousandfold difference in proton concentration), which could have powered early cellular metabolism.
This proton gradient may have led to the formation of the first cells, using hydrogen as a power source to reduce CO2.
The Role of Iron-Sulfur Clusters
Early life likely harnessed the proton gradient through natural iron-sulfur clusters present in these alkaline vents, which acted as electron shuttles.
These clusters helped convert hydrogen into protons and electrons, which then reduced CO2 to formic acid, and over time, more complex carbon-based molecules.
This process could have contributed to the development of primordial cell membranes, which were initially very leaky but became more efficient over time.
concept of pH and illustrates how proton concentrations differ across environments
pH Definition:
The pH scale is defined by the equation
pH=−log 10 [H + ], where [ H + ] [H + ] is the concentration of hydrogen ions (protons).
Each pH unit represents a 10-fold change in proton concentration. This means that as pH decreases by 1 unit, the concentration of hydrogen ions increases tenfold.
Comparison of Environments:
The Hadean ocean (around 4 billion years ago) is depicted with a pH of 6, indicating a more acidic environment compared to modern oceans.
Alkaline hydrothermal vents (pH of 9) represent a more basic or alkaline environment.
The image illustrates that the Hadean ocean had 1000 times more protons (H+) than the alkaline vents, based on a three-unit pH difference (pH 6 vs. pH 9).
Modern pH Examples:
The scale on the right provides modern examples of pH levels:
Sea water today has a pH of 8, which is slightly alkaline.
Human blood has a pH of around 7.4, which is neutral to slightly alkaline.
Alkaline vents have a pH around 9, making them a favorable location for certain types of chemical reactions that might have contributed to early life.
More acidic substances include things like grapefruit juice (pH 3) and battery acid (pH 0).
Environmental Relevance for Early Life:
The Hadean ocean and hydrothermal vents are thought to have been potential environments where early life could have originated. The difference in proton concentration between these environments might have been harnessed by primitive cells to drive metabolic processes, similar to how modern cells use proton gradients to produce ATP.
This proton gradient across environments could have provided an energy source for early life forms, allowing for chemical reactions that contributed to the formation of basic organic molecules.
Key Points:
1. Proton Gradients and ATP Production:
The image shows the interaction between the early protocell and the surrounding environment, particularly the difference in pH between the Hadean ocean (pH 6) and the alkaline hydrothermal vent (pH 9).
This natural pH gradient created a proton gradient, which protocells could harness to drive the production of ATP via ATP synthase, an enzyme responsible for ATP production in modern cells.
- Iron-Sulfur Catalysis: Early metabolism was likely catalyzed by iron-sulfur centers, which acted as primitive catalysts for redox reactions. In this image, the ferredoxin (Fd) complex still plays a key role in transferring electrons and driving metabolic reactions. These iron-sulfur centers are now integrated into proteins, which evolved to stabilize and optimize catalytic processes within the protocell.
- Natural Proton Gradients: The natural proton gradient provided by the alkaline vent allowed protons (H + + ) to flow across the protocell membrane, powering ATP production. Protons move from the acidic ocean (high proton concentration, pH 6) to the alkaline vent environment (low proton concentration, pH 9), allowing ATP synthase to utilize the flow of protons to convert ADP and inorganic phosphate into ATP.
- CO2 Reduction and Metabolism: Early protocells used CO2 as a carbon source and H2 as an energy source to drive metabolic reactions. These metabolic processes allowed the protocell to produce simple organic compounds (Cx Hy Ox ), essential for building cellular structures like lipids, proteins, and nucleic acids. The protocell membrane was still “leaky,” meaning it wasn’t fully impermeable, allowing protons and other molecules to pass through more freely than in modern cells. ATP and Metabolism: Once ATP was produced using the proton gradient, it could be used to fuel other metabolic processes inside the protocell, contributing to the synthesis of compounds necessary for cellular function, such as lipids, nucleic acids, and proteins.
Catabolic reactions
Break down large molecules.
Provide energy for ATP (adenosine triphosphate).
Anabolic reactions
Use small molecules to build larger ones.
Require energy.
Entropy vs enthalpy
Entropy (S) is about the disorder or randomness of particles and energy distribution within a system.
Enthalpy (H) is about the total heat content or energy in a system under constant pressure, often related to heat exchange during reactions.
First Law of Thermodynamics.
Higher Energy to Lower Energy: The slide with the meerkat at the top and bottom represents a system going from a higher energy state to a lower energy state, which involves the release of energy. This is shown with the phrase “energy released.”
ΔH (Change in Enthalpy) is Negative: When the final state has less energy than the initial state, the change in enthalpy (ΔH) is negative. This indicates that the system has released energy into the surroundings, as denoted by “Energy released.”
Second Law of Thermodynamics
Entropy increases: The statement at the top mentions that the entropy, or disorder, of any closed system that is not in thermal equilibrium, almost always increases. This is a fundamental concept in thermodynamics.
Less disorder to more disorder: The boxes represent a system with particles. The top box shows the particles more clustered together (less disorder), while the bottom box shows them more spread out (more disorder), indicating an increase in entropy as the system progresses towards greater disorder.
ΔS (change in entropy) is positive: The equation highlights that the final state of the system has higher entropy than the initial state, which results in a positive change in entropy (ΔS > 0).
For a reaction to move towards more organization (decreasing entropy,
ΔS becomes negative), the enthalpy change (ΔH) must be negative enough to counteract the term TΔS. This is particularly important in reactions that create order from disorder (such as crystallization), where the entropic term opposes the reaction.
ATP to ADP Conversion
Key Points:
ATP to ADP Conversion:
ATP is broken down into ADP and an inorganic phosphate (orthophosphate), releasing a large amount of free energy.
The standard free energy change (ΔG°’) for this reaction is approximately -30.5 kJ/mol, which means it is highly exergonic (spontaneous) and releases energy that the cell can use for various processes.
Repulsive Charge Density:
ATP has a high negative charge density due to its three phosphate groups, which repel each other. This creates instability in the molecule.
When ATP is hydrolyzed into ADP, one phosphate group is released, lowering the repulsive charge density and stabilizing the molecule.
Resonance Stabilization of Orthophosphate:
The orthophosphate (Pi) produced in this reaction can resonate between multiple structures, further stabilizing it. This increased resonance stabilization contributes to the large negative enthalpy (ΔH) of the reaction, making the process highly favorable.
Gibbs Free Energy Equation: The image shows the Gibbs free energy equation:
ΔG=ΔH−TΔS
ΔG is negative, indicating that the reaction is spontaneous.
ΔH (enthalpy change) is negative, meaning the reaction releases heat.
TΔS (entropy change) is positive, indicating that the system becomes more disordered (since energy is released, increasing entropy).
Gibbs Free Energy (G)
This is the energy available to do work in a system at constant temperature and pressure. The equation is represented as: ΔG=ΔH−TΔS
Factors Affecting ΔG:
ΔH (change in enthalpy): The internal energy change of the system, often related to heat release or absorption. A negative ΔH indicates an exothermic reaction (releases heat).
T (temperature): This amplifies the impact of entropy (TΔS) on the overall free energy.
ΔS (change in entropy): A measure of disorder or randomness in the system. A positive ΔS means the system is becoming more disordered, which generally favors spontaneity.
ΔG is Negative:
If ΔG is negative, the reaction proceeds spontaneously in the forward direction, as the system can release free energy to do work. This is shown by the slide metaphor, where moving from a higher energy to a lower energy state is favored.
In this case, ΔH is negative (exothermic, heat is released), and ΔS is positive (increased disorder). Together, these factors make ΔG negative, which means the reaction is spontaneous.
A reaction towards a “more organized” state (lower entropy) can only occur if the change in enthalpy (ΔH) is sufficiently negative to override the decrease in entropy (TΔS). Explanation: More organized reactions involve decreasing entropy (ΔS), meaning the system becomes more ordered. This is typically unfavorable because natural processes tend to move towards greater disorder. However, these reactions can still proceed if they are exothermic (ΔH is negative), meaning they release enough heat to make the total Gibbs free energy (ΔG) negative. The term TΔS represents the influence of temperature and entropy in the Gibbs free energy equation (ΔG=ΔH−TΔS). For a reaction to occur spontaneously (with a negative ΔG), the exothermic enthalpy change (ΔH) must outweigh the unfavorable decrease in entropy (TΔS).
Thermodynamics behind ATP hydrolysis to ADP and orthophosphate
ATP Hydrolysis and Large Negative ΔG:
The process of ATP hydrolysis releases a significant amount of energy, represented by a large negative ΔG°’ value (-30.5 kJmol⁻¹). This indicates that the reaction is energetically favorable and spontaneous.
Charge Repulsion:
ATP has a higher negative charge density due to the closely packed phosphate groups, which repel each other. This makes ATP less stable. ADP, after hydrolysis, has a lower negative charge density, making it more stable.
Orthophosphate (Inorganic Phosphate, Pi):
After hydrolysis, the orthophosphate (Pi) can resonate between several different structures. This resonance stabilization lowers the overall energy (enthalpy) of the system, making the products more stable compared to ATP.
Free Energy Equation:
The equation ΔG = ΔH - TΔS suggests that the change in free energy (ΔG) depends on the change in enthalpy (ΔH) and the change in entropy (ΔS) multiplied by temperature (T).
In this case, both ΔH (enthalpy change) is negative (energy release from breaking bonds), and ΔS (entropy change) is positive (increase in disorder), contributing to the large negative ΔG.
Difference between ATP and redox reactions
ATP Phosphorylation (Left Side):
ATP donates a phosphoryl group (PO₄²⁻) to another molecule, shown here with a sugar molecule.
In this process, no electron transfer occurs. The main action is the addition of a phosphate group to the target molecule, which is a common mechanism in many metabolic pathways, such as phosphorylation reactions.
This addition changes the molecule’s properties, such as increasing its energy potential or altering its shape and function, as seen in many cellular processes like glycolysis.
NAD⁺ Electron Transfer (Right Side):
NAD⁺ (Nicotinamide adenine dinucleotide) undergoes a reduction reaction. In this process, electrons (e⁻) are transferred to NAD⁺, converting it to NADH.
This reaction involves the addition of a hydrogen atom (H) along with two electrons (symbolized as e⁻) to NAD⁺. This results in NADH, which carries the electrons to other parts of the cell, typically in processes like oxidative phosphorylation.
NADH is a key electron carrier in cellular respiration and is crucial in generating ATP through the electron transport chain.
Rust formation, focusing on the redox (reduction/oxidation) reaction that occurs between iron and oxygen
Iron (Fe) is oxidized, which means it loses electrons while Oxygen (O₂) is reduced, meaning it gains electrons.
Reduction Potential
The reduction potential is a measure of how likely a chemical species is to gain electrons (be reduced) or lose electrons (be oxidized) when interacting with an electrode. It quantifies the tendency of a species to be reduced or act as an oxidizing agent.
A more positive reduction potential means the species has a higher tendency to gain electrons and be reduced.
How direction of redox reaction can be calculated from reduction potentials
Overall cell potential for a redox reaction involving oxygen (O₂) and iron (Fe²⁺/Fe³⁺) using standard reduction potentials
How proton gradients operate in mitochondria
Proton Gradient (H⁺ Concentration): Proton gradients are created due to differences in pH, which directly relate to hydrogen ion (H⁺) concentrations. Each unit of pH represents a 10-fold difference in H⁺ concentration. In this example, the Hadean ocean has a pH of 6, which is more acidic and contains 1000 times more protons than the alkaline vent (pH 9).
Energy Utilization: The gradient between the Hadean ocean (higher proton concentration, pH 6) and the alkaline vent (lower proton concentration, pH 9) represents a potential energy source. Protons naturally tend to move from areas of higher concentration to areas of lower concentration, and cells can harness this movement to perform energetically costly reactions, like generating ATP.
Mitochondria and ATP Synthesis: In mitochondria, a similar principle applies. During cellular respiration, protons are pumped across the inner mitochondrial membrane, creating a gradient where protons are more concentrated in the intermembrane space than in the matrix. As protons flow back into the matrix through ATP synthase, their movement drives the synthesis of ATP, the energy currency of the cell.
Complex I: NADH-Q Oxidoreductase
Function of Complex I:
Complex I, also known as NADH-Q oxidoreductase, uses reducing power from NADH to create a proton gradient by pumping protons (H⁺) from the mitochondrial matrix into the intermembrane space.
Electrons from NADH are transferred to the coenzyme Q (ubiquinone), passing through a series of iron-sulfur (FeS) clusters and flavin mononucleotide (FMN).
Proton Gradient Creation:
The flow of electrons drives the movement of 4 protons (H⁺) across the inner mitochondrial membrane into the intermembrane space, contributing to the proton motive force needed for ATP synthesis.
Evolutionary Reference:
The image also references LUCA (Last Universal Common Ancestor), where an ancestral version of Complex I (Ech) used an existing proton gradient to power reactions, such as reducing ferredoxin (Fd). This occurred in hydrothermal vent environments, like the Hadean ocean and alkaline vents.
Energy Transfer:
In modern cells, Complex I is part of the electron transport chain, and the energy released during electron transfer is used to pump protons, which are later used by ATP synthase to produce ATP.
Complex II: Succinate-Q Reductase
Function of Complex II:
Complex II, also known as succinate-Q reductase, is part of the electron transport chain and participates in transferring electrons from FADH₂ to coenzyme Q (ubiquinone).
This process occurs after FADH₂ is formed during the oxidation of succinate in the citric acid cycle.
Electron Transfer:
FADH₂ donates two electrons (2e⁻) to Complex II.
The electrons travel through iron-sulfur (FeS) clusters and are passed on to coenzyme Q, which transports them to Complex III.
Proton Pumping:
Unlike Complex I, Complex II does not pump protons (H⁺) across the membrane, so it contributes fewer protons to the gradient used for ATP synthesis.
Energy Yield:
Since no protons are pumped by Complex II, the energy yield from FADH₂ (which passes through Complex II) is lower compared to NADH, as fewer protons contribute to the proton gradient driving ATP synthesis.
Complex III: Q-Cytochrome C Oxidoreductase
Function of Complex III:
Complex III, also known as Q-cytochrome c oxidoreductase, transfers electrons from coenzyme Q (ubiquinone) to cytochrome c.
It accepts electrons from both Complex I and Complex II (via reduced ubiquinone, QH₂).
Electron Transfer:
Electrons are transferred through a series of proteins, including iron-sulfur clusters (FeS), cytochrome b, and cytochrome c₁.
The electrons are passed from ubiquinone (Q) to cytochrome c (C), a mobile electron carrier that moves to Complex IV.
Proton Pumping:
During this process, 4 protons (H⁺) are pumped from the mitochondrial matrix into the intermembrane space, contributing to the proton gradient that drives ATP synthesis.
Energy Contribution:
Complex III is essential for maintaining the proton gradient, which is necessary for ATP production through chemiosmosis.
Mice need brown fat to keep them warm
How do humans survive the cold?
Humans also have brown tissue
Non-chiral carbons d-glucose and d-ribose
D-glucose:
- Open Chain Form (left):
D-glucose is a six-carbon aldose sugar, with an aldehyde group (–CHO) at carbon 1.
- The hydroxyl (–OH) groups are attached to carbon atoms in a specific pattern (right-left-right-right).
Closed Ring Form (right):
- D-glucose commonly forms a six-membered ring (a pyranose), where the aldehyde group at C1 reacts with the hydroxyl group on C5.
- In the ring form, carbon 1 (the anomeric carbon) can either have the hydroxyl group pointing up (beta form) or down (alpha form).
- D-ribose:
- Open Chain Form (left):
D-ribose is a five-carbon aldose sugar with an aldehyde group at carbon 1.
It is a key component of nucleic acids (like RNA).
Closed Ring Form (right):
D-ribose forms a five-membered ring (a furanose), where the aldehyde group at C1 reacts with the hydroxyl group on C4.
- Like glucose, the anomeric carbon (C1) can have two configurations (alpha and beta).
D and L isomers
D-Glucose:
In D-glucose, the hydroxyl group on carbon 5 (C5) is oriented to the right.
This determines the molecule’s classification as a D-isomer.
- L-Idose:
In L-idose, the hydroxyl group on carbon 5 (C5) is oriented to the left.
This orientation makes it an L-isomer.
Enantiomers and diastereoisomers difference
Enantiomers are non-superimposable mirror images of each other. Diastereomers are stereoisomers that are not mirror images of each other and are also non-superimposable.
The open chain forms exist in equiibrium with closed ring forms
The Fischer projection represents the linear form of D-glucose.
The Haworth projection represents the cyclic form (pyranose).
If the group is on the left side, it will be above the plane of the ring. If the group is on the right side, it will be below the plane of the ring.
Anomeric forms (α and β) when D-glucose forms a ring structure
Open-Chain Form to Closed-Ring Form:
The left side shows D-glucose in its open-chain form.
When the linear form of D-glucose closes to form a ring (pyranose), the hydroxyl group on carbon 5 (C5) reacts with the carbonyl group on carbon 1 (C1) to create a cyclic structure.
This process creates a new stereocenter at C1, known as the anomeric carbon.
2. Formation of Anomers:
The cyclic form of glucose can exist as two anomers: α and β, depending on the orientation of the hydroxyl group (–OH) attached to the anomeric carbon (C1).
α-D-glucopyranose: The hydroxyl group at C1 is positioned below the plane of the ring (on the opposite side of the CH₂OH group at C6).
β-D-glucopyranose: The hydroxyl group at C1 is positioned above the plane of the ring (on the same side as the CH₂OH group at C6).
Cellulose Structure
Polysaccharide made up of repeated units of β-D-glucose. The glucose molecules are connected by β-1,4-glycosidic bonds, meaning the hydroxyl group on carbon 1 of one glucose monomer is linked to the hydroxyl group on carbon 4 of the next glucose monomer.
In plant cells, cellulose forms long chains that are bundled into microfibrils, which are embedded in the cell wall to provide structural support.
These microfibrils give strength and rigidity to the plant cell wall, making cellulose a key component in the overall structure of plants.
The β-1,4 linkages allow cellulose to form straight chains that can form hydrogen bonds with adjacent chains, leading to a highly structured and stable network.
A: In low oxygen conditions (such as the last moments of a sprint), pyruvate is converted into lactate.
B: In normal oxygen conditions (like during a slow, long-distance run), pyruvate enters the mitochondria, where it is fully oxidized for more ATP production through aerobic respiration.
How does glycolysis produce energy? The first way is:
Directly through Substrate-level Phosphorylation:
The term refers to the direct production of ATP during glycolysis. In this process, a phosphate group is transferred directly from a substrate molecule to ADP, forming ATP.
This is distinct from oxidative phosphorylation, where ATP is produced using a proton gradient in mitochondria.
Diagram Explanation:
The flow from glucose to pyruvate represents glycolysis, the metabolic pathway that breaks down glucose into pyruvate.
During this process, ADP is converted to ATP by the addition of a phosphate group.
The right-side flow shows ADP being phosphorylated to ATP, emphasizing direct ATP generation.
Whippet Dog Analogy:
The whippet dog going down a slide is likely used to represent the energy release in a spontaneous reaction (much like how ATP is formed by substrate-level phosphorylation in glycolysis).
The second image with molecules (perhaps ATP or glucose breakdown products) represents the molecular transformation happening during the energy release process.
The 5 metabolic fates of pyruvate in cellular metabolism
Pyruvate Hub: Pyruvate is a central molecule in metabolism and can enter multiple pathways depending on the cellular conditions and the organism’s needs.
Pathways from Pyruvate:
1. Alanine Formation: Pyruvate can be converted into alanine through transamination.
2. Oxaloacetate Formation (Gluconeogenesis): Pyruvate can be converted into oxaloacetate, an intermediate in gluconeogenesis and the citric acid cycle.
3. Ethanol (Fermentation in Yeast & Bacteria): In anaerobic conditions in yeast and bacteria, pyruvate is converted to ethanol via acetaldehyde.
4. Lactate Formation (Fermentation in Animals): In the absence of oxygen (anaerobic conditions), pyruvate is converted to lactate.
5. Acetyl-CoA (Krebs Cycle): In the presence of oxygen, pyruvate is converted to acetyl-CoA, which enters the Krebs cycle (citric acid cycle) for aerobic respiration, producing ATP.
Glycolysis and Gluconeogenesis: Pyruvate is formed at the end of glycolysis (blue section), while gluconeogenesis (green section) can regenerate glucose from pyruvate under certain conditions, especially during fasting.
Fuel and Oxygen: Pyruvate can be further oxidized in the mitochondria (Krebs cycle) when oxygen is available, producing energy in the form of ATP.
Purpose of the Pyruvate-Alanine Cycle (1st door)
This cycle is crucial for nitrogen balance and energy metabolism. It allows muscles to rid themselves of nitrogen (a byproduct of protein breakdown) without accumulating toxic ammonium, and it supplies the liver with substrates for glucose production.
Energy Transfer:
The cycle helps ensure that muscles continue to receive glucose for energy, especially during times of high energy demand, such as exercise, when muscles are breaking down protein.
Difference Between Muscle and Liver:
Muscle cells are specialized for glycolysis and energy production, while the liver has a more central role in maintaining overall metabolic balance, including glucose and nitrogen levels.
Pyruvate to Oxaloacetate (2nd door)
Pyruvate is a three-carbon molecule produced from glucose through glycolysis.
When there is a lot of acetyl-CoA in the cell, the cell needs oxaloacetate to enter the gluconeogenesis pathway, rather than producing more acetyl-CoA for the Krebs cycle.
The enzyme pyruvate carboxylase facilitates the conversion of pyruvate to oxaloacetate. This step requires:
ATP (energy input),
CO₂ (carbon dioxide).
This reaction adds a carboxyl group to pyruvate, forming the four-carbon molecule oxaloacetate.
Role of Oxaloacetate:
Gluconeogenesis: Oxaloacetate is a precursor for the synthesis of glucose in the liver during times of fasting or intense exercise.
Krebs Cycle: If energy is needed, oxaloacetate can combine with acetyl-CoA to form citrate and continue through the Krebs cycle for ATP production.
Fermentation and Glycolysis
Glycolysis is the process where glucose (C₆H₁₂O₆) is broken down into pyruvate (C₃H₄O₃), generating ATP (energy) for the cell.
Oxygen Availability:
Under aerobic conditions (with oxygen), pyruvate can be fully oxidized into CO₂ and H₂O via the Krebs cycle and oxidative phosphorylation, maximizing ATP production.
Without oxygen (anaerobic conditions), cells rely on fermentation to regenerate NAD⁺, allowing glycolysis to continue.
Types of Fermentation:
Ethanol Fermentation:
Occurs in yeast and some bacteria.
Pyruvate is converted into ethanol and CO₂.
This process helps regenerate NAD⁺, which is crucial for glycolysis to keep producing ATP in the absence of oxygen.
Lactate Fermentation:
Occurs in human muscles and some bacteria.
Pyruvate is reduced to lactate (lactic acid).
Similar to ethanol fermentation, this process regenerates NAD⁺, which keeps glycolysis running during anaerobic conditions, such as intense exercise when oxygen supply is limited.
Why Fermentation is Necessary:
Regenerates NAD⁺: NAD⁺ is a cofactor required for glycolysis to continue. During glycolysis, NAD⁺ is reduced to NADH, and fermentation helps convert NADH back to NAD⁺.
Prevents Energy Crisis: Without oxygen, cells cannot produce energy through the Krebs cycle and oxidative phosphorylation, which are the main sources of ATP. Fermentation allows ATP production through glycolysis, albeit less efficiently, ensuring some energy is available to sustain the cell.
Overview of aerobic respiration
Role of Pyruvate Dehydrogenase
Pyruvate from Glycolysis:
In the cytosol, glucose is converted to pyruvate through glycolysis, generating 2 ATP via substrate-level phosphorylation.
Pyruvate, a 3-carbon molecule, enters the mitochondrial matrix via a transport protein.
Pyruvate Dehydrogenase Complex:
Once inside the mitochondrial matrix, pyruvate is acted on by the pyruvate dehydrogenase complex. This enzyme catalyzes the irreversible conversion of pyruvate into acetyl-CoA.
The Three Steps of the Pyruvate Dehydrogenase Reaction:
Step 1: Pyruvate is decarboxylated, meaning it loses a carbon atom in the form of CO₂.
Step 2: The remaining 2-carbon molecule is oxidized, reducing NAD⁺ to NADH and forming acetyl.
Step 3: The acetyl group binds to coenzyme A (CoA), forming acetyl-CoA.
Acetyl-CoA in the Krebs Cycle:
Acetyl-CoA, the product of this reaction, enters the Krebs cycle, where it combines with oxaloacetate to form citrate and begins a series of reactions that produce ATP, NADH, FADH₂, and CO₂.
Krebs cycle
Entry into the Krebs Cycle:
Pyruvate Dehydrogenase converts pyruvate (C3) into acetyl-CoA (C2) in the mitochondrial matrix. This reaction produces NADH and releases one molecule of CO₂.
Steps of the Krebs Cycle:
Citrate Formation:
Acetyl-CoA (C2) combines with oxaloacetate (C4) to form citrate (C6).
Isomerization:
Citrate is rearranged into its isomer, isocitrate.
First Oxidation:
Isocitrate is oxidized, producing one molecule of NADH and releasing CO₂. This results in a five-carbon compound (C5).
Second Oxidation:
The C5 compound is oxidized again, producing another NADH and releasing a second molecule of CO₂. This results in a four-carbon compound (C4) attached to Coenzyme A (CoA).
ATP Formation:
The high-energy bond between CoA and the C4 compound is cleaved, generating ATP (or GTP).
FADH₂ Production:
The C4 compound is oxidized again, reducing FAD to FADH₂.
Final NADH Production:
The C4 compound undergoes another oxidation, producing one more molecule of NADH, and regenerating oxaloacetate (C4), which is ready to combine with another acetyl-CoA to start the cycle again.
Products of the Krebs Cycle:
For each Acetyl-CoA molecule (which came from one pyruvate):
3 NADH (electron carriers)
1 FADH₂ (electron carrier)
1 ATP (or GTP)
2 CO₂ (waste)
Since one glucose molecule produces two pyruvate molecules (and thus two acetyl-CoA molecules), the Krebs cycle turns twice for each glucose, doubling the outputs.
Overall energy yield (ATP, NADH, and FADH₂) produced during cellular respiration from one glucose molecule
lycolysis (Cytosol):
Glucose (C₆H₁₂O₆) is split into two molecules of pyruvate in the cytosol.
Yield from glycolysis:
2 ATP (substrate-level phosphorylation)
2 NADH (produced during the oxidation of glucose)
2. Pyruvate Dehydrogenase (Mitochondria):
In the mitochondrial matrix, pyruvate is converted into acetyl-CoA.
Yield from pyruvate dehydrogenase (per glucose molecule, which produces 2 pyruvate):
2 NADH (one per pyruvate)
2 CO₂ (waste product)
3. Krebs Cycle (Citric Acid Cycle):
Each acetyl-CoA enters the Krebs cycle, which takes place in the mitochondrial matrix.
Yield from the Krebs cycle (per glucose molecule, which generates 2 acetyl-CoA):
2 ATP (substrate-level phosphorylation)
6 NADH
2 FADH₂
4 CO₂ (waste product)
Total Yield from One Glucose:
4 ATP (2 from glycolysis, 2 from the Krebs cycle)
10 NADH (2 from glycolysis, 2 from pyruvate dehydrogenase, 6 from the Krebs cycle)
2 FADH₂ (from the Krebs cycle)
Summary of the overall ATP yield from cellular respiration
ATP Yield by Process:
Glycolysis (Cytosol):
Glucose is broken down into 2 pyruvate.
Net Yield:
2 ATP (substrate-level phosphorylation)
2 NADH
Pyruvate Oxidation (Mitochondrial Matrix):
Each pyruvate (from glycolysis) is converted into acetyl-CoA, releasing CO₂.
Net Yield:
2 NADH (one per pyruvate)
Krebs Cycle (Mitochondrial Matrix):
Acetyl-CoA enters the cycle, producing CO₂, NADH, FADH₂, and ATP.
Net Yield (for 2 acetyl-CoA per glucose):
6 NADH
2 FADH₂
2 ATP (substrate-level phosphorylation)
Electron Transport Chain (ETC) and Oxidative Phosphorylation:
The NADH and FADH₂ produced in glycolysis, pyruvate oxidation, and the Krebs cycle donate electrons to the ETC.
This process drives the production of a large amount of ATP.
Net Yield:
26–28 ATP (depends on the efficiency of the ETC and transport mechanisms)
Total Yield from One Glucose:
2 ATP from glycolysis
2 ATP from the Krebs cycle
26–28 ATP from oxidative phosphorylation (driven by NADH and FADH₂)
Total: 30–32 ATP
Efficiency of respiration versus glycolysis
Free energy changes in the glycolysis pathway
Hexokinase Reaction (Step 1):
Glucose is phosphorylated to glucose-6-phosphate (G6P) using 1 ATP.
Free Energy Change: -33.9 kJ/mol (irreversible).
ATP Use: 1 ATP consumed.
Phosphoglucose Isomerase (Step 2):
G6P is isomerized to fructose-6-phosphate (F6P).
Reversible reaction with a small ΔG⁰ change.
Phosphofructokinase Reaction (Step 3):
F6P is phosphorylated to fructose-1,6-bisphosphate (F1,6BP) using 1 ATP.
Free Energy Change: -18.8 kJ/mol (irreversible).
ATP Use: Another ATP consumed (total: 2 ATP).
Aldolase (Step 4):
F1,6BP is split into two three-carbon molecules: glyceraldehyde-3-phosphate (GADP) and dihydroxyacetone phosphate (DHAP). DHAP is converted into GADP.
ΔG⁰ is low, making it reversible.
Glyceraldehyde-3-Phosphate
Dehydrogenase (Step 5):
GADP is oxidized to 1,3-bisphosphoglycerate (1,3BPG), producing NADH.
NADH Production: 2 NADH per glucose molecule (one per GADP).
Phosphoglycerate Kinase (Step 6):
1,3BPG donates a phosphate group to ADP, forming 3-phosphoglycerate (3PG) and 2 ATP (one per GADP).
ATP Generation: 2 ATP per glucose (recovering the 2 ATP spent earlier).
Phosphoglycerate Mutase (Step 7):
3PG is converted to 2-phosphoglycerate (2PG), a reversible reaction.
Enolase (Step 8):
2PG is dehydrated to form phosphoenolpyruvate (PEP), a high-energy compound.
Pyruvate Kinase Reaction (Step 9):
PEP donates a phosphate to ADP, producing pyruvate and 2 ATP (one per GADP).
Free Energy Change: -23 kJ/mol (irreversible).
ATP Generation: 2 more ATP per glucose.
The Cori Cycle
In the Muscles (Anaerobic Conditions):
During intense exercise or anaerobic conditions, glucose is converted to pyruvate via glycolysis, generating 2 ATP for energy.
Since oxygen is limited, pyruvate cannot enter the Krebs cycle. Instead, it is converted into lactate.
Lactate is produced to regenerate NAD⁺, which is necessary for glycolysis to continue and produce more ATP.
Transport to the Liver:
The lactate produced in the muscles is transported through the bloodstream to the liver.
Accumulation of lactate in the muscles can lead to muscle fatigue, which is why it is transported away for further processing.
In the Liver (Gluconeogenesis):
In the liver, lactate is converted back into pyruvate, which is then used to synthesize glucose via gluconeogenesis.
This process consumes 6 ATP per glucose molecule (the cycle is energy-demanding for the liver).
The newly formed glucose is released back into the bloodstream.
Glucose Returns to the Muscles:
The glucose produced in the liver travels through the blood to the muscles, where it can be used to fuel glycolysis again, providing 2 ATP per cycle.
This allows the muscles to continue producing energy even in the absence of sufficient oxygen.
Bypass 1: Pyruvate carboxylase and PEPCK
Pyruvate Carboxylase catalyzes the conversion of pyruvate into oxaloacetate. This reaction occurs in the mitochondria and requires CO₂, ATP, and biotin as cofactors. It is allosterically activated by acetyl-CoA (shown on the left side).
Oxaloacetate is then reduced to malate via a mitochondrial enzyme, with the simultaneous oxidation of NADH to NAD⁺. Malate exits the mitochondria into the cytosol.
In the cytosol, malate is reoxidized to oxaloacetate, with the reduction of NAD⁺ to NADH.
Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the decarboxylation and phosphorylation of oxaloacetate to form phosphoenolpyruvate (PEP), with GTP as the phosphate donor (depicted in the circled GTP/GDP reaction). This step bypasses pyruvate kinase from glycolysis.
Regulation of bypass 1 in gluconeogenesis
Pyruvate to Oxaloacetate:
Pyruvate is converted into oxaloacetate by pyruvate carboxylase in a reaction that consumes ATP. This step is positively regulated by Acetyl-CoA (as indicated in the diagram).
Oxaloacetate to PEP:
Oxaloacetate is then converted into PEP by phosphoenolpyruvate carboxykinase (PEPCK). This reaction uses GTP and produces GDP.
Malate Shuttle:
The conversion of oxaloacetate into malate and back into oxaloacetate occurs via the NADH/NAD⁺ cycle, which is a part of the malate shuttle. This step ensures that NADH is available in the cytosol for subsequent reactions in gluconeogenesis.
Regulation of Pyruvate Kinase:
The diagram shows that pyruvate kinase (which converts PEP back to pyruvate in glycolysis) is inhibited, preventing the reverse of this pathway from occurring.
