Lecture Notes on Energy and Metabolism

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Module 9A: Metabolism and Energy 1

Module Goals

• Understand and memorize the structure of ATP and the function of each part.
• Understand the structure of mitochondria and its role in ATP production.
• Most ATP is made in the mitochondria during cellular respiration.
• Glycolysis in the cytoplasm produces only 2 net ATP.
• Mitochondria involvement in cellular respiration can lead to at least 34 ATP.
• Understand why mitochondria have a double membrane structure with folds (cristae) for increased surface area.
• Increased surface area serves as anchor points for ATP synthase.
• ATP synthase is the enzyme that makes ATP.
• Understand the relationship between bond length and potential energy stored in the bond.
• Revisit electronegativity.
• Understand the 1st and 2nd laws of thermodynamics and their application.
• Understand the two major categories of metabolism: catabolism and anabolism.

Case Study: DNP (2,4-Dinitrophenol)

• A bodybuilder died after taking DNP, a weight loss drug.
• DNP was banned in 1938 due to dangerous side effects and deaths.
• DNP was initially popular in the 1930s for causing weight loss.
• It leads to an average of 11% increase in metabolic rates per 100mg.
• DNP is now banned as a weight loss drug in the United States.
• The United Kingdom labels DNP as a hazardous chemical.
• Deaths attributed to DNP consumption were recorded as early as the early 1900s, resurfaced in the 1930s, and re-emerged in the early 2000s.
• DNP affects the electron transport chain and mitochondrial membrane integrity, leading to high fevers.
• More details on DNP mechanism are available in a scientific journal article.

Energy Requirements of Cells

• All cells require the input of free energy.
• Free energy is the energy available for work.
• Autotrophs:
  • Lithotrophs: organisms that extract inorganic compounds from rocks and use electrons to produce organic molecules.
  • Phototrophs: organisms like plants that convert sunlight into chemical energy by making organic molecules.
• Heterotrophs: organisms like mammals that consume other organisms and extract potential energy from their bonds.
• Electrons are extracted and used by the mitochondria, specifically ATP synthase.
• ATP synthase uses ADP (adenosine diphosphate) and inorganic phosphate to form ATP.
• All energy from the environment is processed through metabolic pathways to the electron transport chain.
• The electron transport chain leads to ATP synthase creating a gradient of protons that ultimately makes ATP.

ATP: The Energy Currency of the Cell

• ATP is used for:
  • Synthesizing cellular macromolecules (DNA, RNA, proteins, polysaccharides).
  • Synthesizing other cellular constituents (membrane phospholipids, metabolites).
  • Cellular movements (muscle contraction, cell crawling, chromosome movement during mitosis).
  • Transport of molecules against concentration gradients (primary active transport).
  • Generating electric potential across a membrane (nerve function).
• The separation of the last phosphate group from ATP releases energy to perform cellular functions which some of that energy is converted to heat.

Carbohydrate Metabolism

• Focus on carbohydrate metabolism, especially glucose.
• Carbohydrates contain considerable energy stored within their bonds (C-C and C-H bonds).
• Combustion reaction: Carbohydrate + Oxygen -> Carbon Dioxide + Water + Energy.
• Energy here refers to total energy (enthalpy), not just free energy.
• Not all energy from the combustion reaction can be harnessed, instead, some of it is released as heat.
• Reverse of this reaction is photosynthesis: Carbon Dioxide + Water + Light Energy -> Complex Carbohydrates + Oxygen.
• ATP creation involves ADP and inorganic phosphate, not direct conversion of carbohydrates.
• Glucose is broken down to extract electrons, which are fed into the electron transport chain.
• The electron transport chain is used by ATP synthase, which uses ADP and inorganic phosphate to bring them together and form that bond.
• The breaking of bonds in glucose releases energy slowly, and it's captured by the cell by making new bonds in other molecules.

ATP Structure

• ATP (adenosine triphosphate) consists of a ribose sugar, the base adenine, and three phosphate groups.
• Phosphate groups are named alpha, beta, and gamma.
• Bonds between the phosphate groups are referred to as alpha, beta, and gamma bonds.
• ATP has two high-energy bonds between the beta and gamma phosphate.
• The cell typically breaks the gamma bond to release energy.
• ATP can be thought of as a loaded molecule with potential energy stored in the gamma phosphate bond.
• The release of energy from ATP involves hydrolysis into ADP and inorganic phosphate.

Hydrolysis of ATP

• The release of energy from ATP involves the hydrolysis of ATP into ADP and inorganic phosphate, releasing the gamma phosphate.
• The potential energy or chemical energy of the bond is used to do work.
• It requires energy to break bonds.
• The gamma bond in ATP is unstable which allows the bonds to be broken spontaneously.
• Enzymes facilitate the transition state, lowering the activation energy required to break the bond.
• ATP inside water undergoes hydrolysis to make ADP and inorganic phosphate, releasing free energy.
• Under standard lab conditions: ATP hydrolysis releases approximately -7.3 kilocalories per mole.
• Standard conditions: 25°C, pH 7.4, salt concentrations close to cell-like conditions.
• Under cellular conditions: 37°C, pH 7.4, with various proteins and molecules, energy released is approximately -14 kilocalories per mole.
• The difference is attributed to the presence of proteins and molecules in the cytoplasm which allows for more energy to be extracted.
• ATP is highly unstable and spontaneously dissociates into ADP and inorganic phosphate, releasing energy as heat that cannot be used.
• Cells require a large number of ATP mainly because of all the different reactions ATP participates in and also because ATP spontaneously dissociates.

Cellular Respiration

• Eukaryotic cells generate most of their ATP via cellular respiration.
• Cellular respiration steps:
  1. Glycolysis: occurs in the cytoplasm.
  2. Pyruvate oxidation: occurs in the mitochondrial matrix.
  3. Krebs cycle (TCA cycle): occurs in the mitochondrial matrix.
  4. Electron transfer chain: occurs in the inner mitochondrial membrane.
• The last step requires oxygen to capture electrons.
• Glucose is transported into the cell via transporters.
• Glycolysis breaks down glucose into pyruvates, yielding 2 ATP molecules.
• Pyruvate is further broken down in the mitochondrial matrix through the Krebs cycle releasing electrons.
• Electron carriers (e.g., NAD+) are reduced (e.g., NADH) and transport electrons to the electron transport chain.
• The electron transport chain produces most of the ATP (around 32 ATP).
• Glycolysis is anaerobic but less efficient.
• Cellular respiration converts glucose into carbon dioxide and water and yields approximately 38 ATP molecules.
• The exact number of ATP molecules made is an active field of research.
• The cellular respiration, in particular, the last part in the mitochondria is where the most ATP is made versus just the 2 that are made in the cytoplasm.

Efficiency of Cellular Respiration

• Assuming -7.3 kilocalories per mole of ATP, approximately -233.6 kilocalories can be recovered from every mole of glucose.
• One mole of glucose represents 686 kilocalories.
• About 34% efficiency.
• This efficiency means the energy that is seen experimentally versus what is expected theoretically.

Common Metabolic Pathways

• Common metabolic pathways are shared among organisms, suggesting a common ancient ancestor.
• 2.4 billion years ago: prokaryotic ancestor lived in an oxygen-free environment where most of the reactions were anaerobic reactions.
• Photosynthetic bacteria appeared and released oxygen around 2.4 billion years ago, making oxygen abundant in the atmosphere.
• Organisms adapted to the presence of oxygen and developed pathways like cellular respiration.
• Regardless of the degree of divergence from the ancient ancestor, all organisms now, so fungi, animalia, plantae, and so on, harvest energy from their environment and convert it to ATP to carry out cellular functions.
• ATP is still the main currency of energy, even though it's unstable.

Electronegativity and Bond Length

• Electronegativity determines whether a bond is polar or nonpolar.
• The nonpolar bonds are longer, slightly longer.
• The cell prefers to break longer bonds because they have more potential energy in them.
• Electronegativity is the tendency of an atom to attract electrons towards itself.
• In a bond between oxygen and hydrogen, oxygen which is more electronegative than hydrogen, pulls electrons towards it.
• Oxygen has a partial negative charge and hydrogen has a partial positive charge.
• The longer the bond length, the greater the potential energy, which is also known as chemical energy.
• The greater the electronegativity difference, the shorter the bond length.
• Oxygen to hydrogen bond electronegativity value = 1.24.
• Carbon to hydrogen bond electronegativity value = 0.35.
• Nonpolar bonds tend to have longer bonds and thus more potential energy in them.
• The cell prefers to break those kinds of bonds because there's more potential energy in them.

Types of Energy

• Energy is the ability to do work.
• Kinetic energy: energy of motion.
• Potential energy includes potential energy, that is stored in a resting state, like a wrecking ball. For example, if it's raised to another higher level, that potential energy is higher because it can cause damage or work if it rolls down or moves to a lower state.
• Potential energy: potential energy that is stored in a spring.
• Chemical energy: is a form of potential energy held in chemical bonds (e.g., carbon-carbon, carbon-hydrogen).
• The bonds between the carbon-carbon and carbon-hydrogen can be thought of as compressed springs, and when they are broken, the springs are relaxed. So energy is released into the environment.
• Organic molecules with high potential energy are used, like carbohydrates for example, to produce ATP.

Laws of Thermodynamics

First Law of Thermodynamics

• Energy cannot be created or destroyed, only transformed.
• The total amount of energy in a system remains constant.
• Energy captured by plants from the sun is converted into chemical energy.
• Matter is converted into kinetic energy.

Second Law of Thermodynamics

• During the transformation of energy, some energy is transformed into heat.
• The heat cannot be used by the cell and increases the entropy of the system.
• Entropy is the degree of disorder or randomness in a system; this type of energy is unavailable to do work.
• Free energy is the energy available to do work.
• All the energy is accounted for in the transformation of one type of energy.
• During that transformation, some of that energy is lost in the form of heat, which contributes to entropy.
• The remaining energy is free energy, which can be used by the cell.
• Free energy is what's used to make ATP.

Metabolism: Catabolism vs. Anabolism

Catabolism

• Breaking down macromolecules (complex polymers) into monomers (individual subunits), such as:
  • Carbohydrates into carbohydrates, broken by beta-1,4 linkages or alpha-1,4 linkages, and so on. So you get these large, complex polymers, these macromolecules.
  • Proteins into amino acids, which are polymers of amino acids linked together by peptide bonds.
  • Fats into fatty acids, which you have these long hydrocarbon tails which can be broken to extract energy.
  • Nucleic acids into nucleotides, composed of individual nucleotides linked together with the phosphodiester bonds.
• Breaking bonds releases chemical energy.

Anabolism

• Building macromolecules from monomers.
• Requires energy input to form bonds.
• ATP is made from catabolism.
• As macromolecules are broken down, energy is captured to form bonds between ADP and inorganic phosphate to make ATP.
• Anabolism occurs via the polymerization of nucleic acids.
• The polymerization of nucleic acids is done during the making of the daughter strand for DNA replication, and the making of the primary transcript in transcription. So anywhere you have the construction of a polymer from monomers, that's anabolism.
• To go the other direction, which is to make macromolecules, for example, nucleic acids, such as the making of the daughter strand for DNA replication or the making of the primary transcript in transcription, that requires the linking of the individual nucleotides, which requires energy input. That is done by the use of ATP, and the individual subunits to make those bonds to finally make the nucleic acids.
• Any building of a polymer from monomers is anabolism (e.g. building of the protein by the formation of the peptide bonds in translation).
• Generally ATP is used in constructing macromolecules.
• Anabolic reactions: small molecules assembled into larger ones. Bond formation requires energy input.
• Catabolic reactions: polymers broken down to release energy stored in bonds holding monomers in polymers.