Energy Metabolism and ATP Production

Electrical Energy

Energy created when loosely attached electrons move from one atom to another due to an applied electric field, creating an electric current.

Nuclear Energy

Energy derived from nuclear reactions that cause changes to the structure of the atomic nuclei, found in sources like the Sun, nuclear reactors, and the Earth's interior.

Mechanical Energy

The energy an object possesses by virtue of its motion (kinetic energy), such as a baseball flying through the air.

Thermal or Heat Energy

The collective, microscopic, kinetic and potential energy of molecules within a substance, like the molecules in a hot cup of coffee.

Radiant Energy

Energy transmitted by light or electromagnetic radiation such as energy received by Earth from the Sun.

Energy

Fuels metabolism and enables cells, muscles, and other body tissues to perform work.

Metabolism

A series of chemical reactions where the product of one reaction is the substrate for the next.

Energy Metabolism

Major reactions by which the body obtains and uses energy from food

Catabolism

processes that release energy by breaking down larger molecules

Anabolism

Processes that use released energy to build larger molecules

Chemical Energy (Metabolism)

Primarily used to produce Adenosine Triphosphate (ATP), with glucose catabolism as the main source.

ATP Structure

2 high energy phosphate bonds that store energy and is released by hydrolysis

Hydrolysis of ATP (ADP)

Splitting one high-energy bond: ATP + H2O ightarrow ADP + Pi + H^+ (yielding adenosine diphosphate and inorganic phosphate).

Hydrolysis of ATP (AMP)

splitting of 2 high energy bonds: ATP + H2O = AMP + PPi (yielding adenosine monophosphate and inorganic pyrophosphate)

ATP "Energy Currency"

Cells contain a limited quantity of ATP (sufficient for seconds of intense exercise) and constantly regenerate it, never fully depleting stores (approx. 30\% remains).

Primary Three ATP Production Systems

Phosphagen System (Immediate), Anaerobic System (Anaerobic glycolysis), Aerobic System (Citric Acid Cycle & Electron Transport Chain).

Phosphagen System Characteristics

Simplest, most immediate, instantaneous energy, low complexity (one-step), very fast maximal rate, very limited capacity, no lag time.

Phosphagen System Mechanism

Creatine phosphate (CP) directly provides a phosphate for ATP resynthesis, catalyzed by Creatine Kinase. Cells store more CP than ATP.

Phosphagen System Reaction

Enzyme: Creatine Phosphokinase creatine phosphate + ADP = creatine + ATP

Anaerobic Pathway Substrate

Only glucose (or glycogen broken down via glycogenolysis) can be used.

Anaerobic Pathway Process

Glucose is broken down to pyruvate. If no oxygen, pyruvate converts to lactic acid.

Anaerobic Pathway ATP Yield

Generates 2 ATP molecules per molecule of glucose.

Lactic Acid Formation Reaction

Pyruvate\,(COO^-, C=O, CH3) \xrightarrow{Lactate\,Dehydrogenase} L-Lactate\,(COO^-, HO-C-H, CH3), with NADH + H^+ oxidized to NAD^+.

Aerobic Pathway Oxygen Requirement

Occurs when oxygen is available.

Aerobic Pathway Efficiency & ATP Yield

highly efficient, produces over 90% of the body’s ATP

Aerobic Pathway Speed & Capacity

Slowest ATP production system, but has an unlimited ability to produce ATP.

Metabolic Pathways in Aerobic Respiration

Glycolysis, Beta-oxidation, Deamination, Citric Acid Cycle (Krebs/TCA), Electron Transport Chain (ETC).

Aerobic Pathway End Products

ATP, carbon dioxide (CO2), and water (H2O).

What happens to pyruvate in glycolysis?

Net result of 2 ATP and 2 pyruvate molecules, with pyruvate then forming acetyl CoA to enter the Citric Acid Cycle.

Citric Acid Cycle Location

Mitochondrial matrix

Citric Acid Cycle Inputs

Products from breakdown of carbohydrates, fats, and amino acids (primarily as acetyl CoA).

Citric Acid Cycle Outputs

CO2, H20, and ATP (indirectly via NADH and FADH2)

Citric Acid Cycle Entry Molecule

Acetyl CoA (a 2-carbon molecule).

Citric Acid Cycle Direct Products per Turn

For each acetyl CoA: 3\,NADH, 1\,GTP (equivalent to ATP), and 1\,FADH_2. Loss of 2 carbons as CO_2.

Citrate Synthase Reaction

Acetyl CoA condenses with Oxaloacetate to form Citrate (first step of Krebs Cycle).

Isocitrate Dehydrogenase Reaction (Krebs)

Isocitrate to Alpha-ketoglutarate, releasing CO2 and producing NADH + H+

Alpha-ketoglutarate Dehydrogenase Complex Reaction (Krebs)

Alpha-ketoglutarate to Succinyl CoA, releasing CO_2 and producing NADH + H^+.

GTP Production (Krebs)

Succinyl CoA to Succinate, catalyzed by Succinate Thiokinase/Synthetase, producing GTP from GDP + P_i.

FADH2 Production (Krebs)

Succinate to Fumarate, catalyzed by Succinate Dehydrogenase, producing FADH_2.

NADH ATP Yield (Old Convention)

Each NADH + H^+ yields 3 ATP.

FADH2 ATP Yield (Old Convention)

Each FADH_2 yields roughly 2 ATP.

NADH ATP Yield (Newer Convention)

Each NADH + H+ yields 2.5 ATP

FADH2 ATP Yield (Newer Convention)

Each FADH_2 yields roughly 1.5 ATP.

Metabolic Pathway Regulation Mechanisms

Lack of substrate(s), accumulation of final product, enzymes (hormonal effects), compartmentalization of reactions.

Lack of Substrate Regulation

Enzymes are only active if certain substrate concentrations are met; insufficient substrate prevents reaction initiation.

Accumulation of Final Product Regulation

High product concentration can inactivate enzymes (often allosteric), slowing or stopping the reaction.

Allosteric Enzymes

Possess allosteric sites (other than active site) where effector molecules bind, causing conformational change to enhance or inhibit enzyme activity. Example: Citrate inhibiting PFK-I.

Hormone Effect on Enzyme Synthesis (Slow)

Hormones regulate enzyme synthesis over minutes/longer. Example: Insulin increases glucokinase synthesis in liver to trap glucose.

Hormone Effect on Enzyme Covalent Modification (Quick)

Hormones trigger rapid covalent modification (e.g., phosphorylation/dephosphorylation) of existing enzymes to activate/deactivate them. Example: Glucagon/cAMP activating Protein Kinase A for catabolic pathways.

Kinase

An enzyme that adds a PO_4 (phosphate) group.

Phosphatase

An enzyme that removes a PO_4 (phosphate) group.

Compartmentalization of Reactions

Localization of metabolic activity to specific parts of the cell (e.g., cytoplasm, mitochondria, lysosomes) or specific tissues.

Reasons for Compartmentalization

Separates opposing pathways (prevents futile cycles) and regulates pathway activity by controlling substrate transport.

Glucokinase (Liver)

Traps glucose in liver (Glucose
ightarrow Glu-6-P). Activated by high glucose/insulin to store glycogen; inhibited by high glucagon. Generally 'off' unless activated by high insulin ('feasting').

Hexokinase (Brain & Muscle)

Traps glucose in brain/muscle (Glucose
ightarrow Glu-6-P). Always active in brain (absolute glucose need). In muscle, inhibited only by accumulating Glucose-6-Phosphate (G-6-P).

Krebs Cycle Regulatory Enzymes

Citrate Synthase, Isocitrate Dehydrogenase, Alpha-ketoglutarate Dehydrogenase Complex.

Citrate Synthase Regulation

Negatively regulated by NADH.

Isocitrate Dehydrogenase Regulation

Negative effectors: High ATP, high NADH. Positive effectors: High ADP, AMP, high NAD^+, Ca^{2+}.

Alpha-ketoglutarate Dehydrogenase Complex Regulation

Negative effectors: NADH, ATP, Succinyl CoA. Positive effector: Ca^{2+}.

Electron Transport Chain (ETC)

Also called the Respiratory Chain, consists of four protein complexes on the inner mitochondrial membrane, transferring electrons to O2 to form H2O.

Electron Carriers in ETC

NADH + H^+ and FADH_2 (reducing equivalents) carry electrons to the ETC.

NADH in ETC

Can be free-floating; NADH diffuses to ETC after NAD^+ is reduced.

FADH2 in ETC

Binds tightly with enzymes (e.g., Succinate Dehydrogenase) in inner mitochondrial membrane, immediately available to ETC at a different entry point.

Chemiosmosis

The coupling of the proton-motive force with ATP synthesis.

Proton Pumping in ETC

Energy from NADH and FADH_2 oxidation pumps H^+ from mitochondrial matrix to intermembrane space against gradients. NADH pumps approx. 10 protons; FADH_2 pumps approx. 6 protons.

ATP Synthase

An enzyme complex in the inner mitochondrial membrane where H^+ flows down its gradient, harnessing potential energy to synthesize ATP from ADP and P_i.

Protons Required per ATP (ETC)

Approximately 4\,H^+ required to produce one ATP molecule (incorporating 3\,H^+ for synthesis and 1\,H^+ for transport).

ATP-ADP Translocase

An antiport transporter allowing ATP out of and ADP into the mitochondrial matrix.

Phosphate Transporter

Allows inorganic phosphate (P_i) to enter the mitochondrial matrix.

Complex I (NADH Dehydrogenase)

Receives electrons from NADH; oxidizes NADH to NAD^+; transfers electrons and protons to Coenzyme Q, pumping 2\,H^+.

Coenzyme Q (Ubiquinone)

Mobile electron carrier accepting electrons from Complex I and II, passing them one at a time.

Complex II (Succinate Dehydrogenase)

Accepts electrons from succinate (Krebs cycle) via bound FAD (FADH_2), transferring them to Coenzyme Q. Does not pump protons.

Complex III (Cytochrome c Reductase)

Receives electrons from Coenzyme Q, transfers to Cytochrome c, contributing to proton pumping.

Cytochromes

Proteins in ETC (b, c, aa_3) with iron (Fe) heme groups that accept (Fe^{3+}
ightarrow Fe^{2+}) and transfer (Fe^{2+}
ightarrow Fe^{3+}) electrons.

Complex IV (Cytochrome c Oxidase)

Receives electrons from Cytochrome c, passes them to O2 (final electron acceptor), forming H2O, and contributes to proton pumping.

ETC ATP Yield Summary (NADH)

NADH 3 ATP (OLD) 2.5 ATP (NEW)

ETC ATP Yield Summary (FADH2)

Every FADH_2 yields 2 ATP (old) or 1.5 ATP (newer).

Krebs Cycle & ETC Linkage

Krebs cycle generates NADH/FADH_2 for ETC, but ETC must regenerate NAD^+/FAD for Krebs cycle to continue, dependent on O*2.

ATP/ADP Ratio Regulation

A high ATP/ADP ratio slows ATP synthase, ETC, and Krebs cycle due to less ADP substrate.

Negative Effectors of Krebs Cycle (ETC link)

Surplus NADH or acetyl CoA inhibits Pyruvate Dehydrogenase (PDHase), and NADH inhibits citrate synthase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase.

Positive Effectors of Krebs Cycle (Energy Demand)

Ca^{2+} powerfully activates PDHase, isocitrate dehydrogenase, and alpha-ketoglutarate dehydrogenase, increasing flux during high energy demand (e.g., muscle contraction).