Chapter 7: Energy Metabolism Notes

Energy Metabolism: Foundations and Pathways

• Learning objectives (Chapter 7):

  • Identify nutrients involved in energy metabolism and the high-energy compound ATP that captures energy released during breakdown.
  • Summarize the main steps in energy metabolism of glucose, glycerol, fatty acids, and amino acids.
  • Explain how excess of energy-yielding nutrients leads to body fat storage and how inadequate intake shifts metabolism.

• The big picture: energy metabolism is the set of chemical reactions that obtain and use energy from food. Every cell needs energy (ATP). The liver is especially metabolically active (Table 7-1 reference in the slides).

• Key terms and definitions

  • Energy (E): capacity to do work; four main types of energy output include heat, mechanical, electrical, and chemical.
  • Metabolism: sum of all chemical reactions in the body; requires fuel (ATP).
  • Anabolism: building up; requires energy.
  • Catabolism: breaking down; releases energy.
  • Fuel: glucose, fatty acids, amino acids.
  • ATP (adenosine triphosphate): high-energy compound that powers cellular activities; contains three phosphate groups; bonds between phosphates are high-energy bonds; hydrolysis releases energy. ATP
    ightarrow ADP + P_i
  • Enzymes and coenzymes: Enzymes accelerate reactions; coenzymes (often vitamins) assist enzymes (e.g., NAD^+ and FAD^+ carry hydrogens to the ETC; ATP synthase makes ATP).

• Transfer of energy in reactions: ATP as the cellular energy currency

  • Energy released during breakdown of glucose, fatty acids, and amino acids is captured by ATP.
  • Coupled reactions increase efficiency and minimize heat loss.
  • ATP formation is tied to energy released from nutrient breakdown: ext{Glycolysis / beta-oxidation / TCA}
    ightarrow ext{NADH, FADH}_2
    ightarrow ext{ETC}
    ightarrow ATP.

• The energy-yielding nutrients and initial processing

  • Four basic macronutrients yield usable energy units:
  • Carbohydrates yield glucose (also fructose and galactose during digestion).
  • Fats yield glycerol and fatty acids.
  • Proteins yield amino acids.
  • Note: all nutrients can be stored as fat if energy intake exceeds needs; not all can be converted back to glucose (e.g., fatty acids cannot be turned into glucose).

• The energy pathways: overview of the major stages

  • Two main sets of processes exist: glycolysis and the subsequent aerobic pathways (TCA cycle and ETC) that occur in mitochondria.
  • Two main new intermediates to know:
  • Pyruvate: a 3-carbon molecule produced by glycolysis; can be used to make glucose (in some tissues) or converted to acetyl CoA in the mitochondria (aerobic).
  • Acetyl CoA: a 2-carbon unit that enters the TCA cycle; cannot be used to make glucose.
  • The three aerobic processes in mitochondria: TCA cycle (Krebs) and Electron Transport Chain (ETC), with glycolysis occurring in the cytosol (anaerobic portion).
  • Notes on where these steps occur: glycolysis is cytosolic and anaerobic; the remaining steps (pyruvate to acetyl CoA, TCA, ETC) are aerobic and occur in mitochondria.

• Glucose to energy: glycolysis, lactate, and pyruvate fate

  • Glycolysis (cytosol, anaerobic): glucose → 2 pyruvate; generates a small amount of ATP and reduces coenzymes that shuttle hydrogen to the ETC.
  • Net outcome for one glucose: ext{Glucose}
    ightarrow 2 ext{pyruvate} + 2 ext{NADH} + 2 ext{ATP (net)}.
  • Pyruvate’s options:
  • Pyruvate to lactate (anaerobic, fast energy): reversible step; lactate can accumulate in muscles causing the burning sensation; lactate is shuttled to the liver via the Cori cycle where it is converted back to glucose.
    • Cori cycle: lactate from muscle → liver → glucose return to muscle.
  • Pyruvate to acetyl CoA (aerobic, slower but sustained energy): irreversible step; occurs in mitochondria; acetyl CoA then enters the TCA cycle.
    • Pyruvate to Acetyl CoA reaction (aerobic): ext{Pyruvate} + ext{CoA} + ext{NAD}^+
      ightarrow ext{Acetyl CoA} + CO_2 + ext{NADH}.
  • Important note: Pyruvate can be converted back to glucose in liver/kidneys, but once it becomes acetyl CoA, the conversion back to pyruvate is not favorable (irreversible).
  • Glycerol can feed into glycolysis downstream to form pyruvate; glycerol is a glycerol backbone from fats.

• Glycerol and fatty acids enter energy metabolism

  • Glycerol (from triglycerides) can be converted to pyruvate and enter the energy pathways.
  • Fatty acids enter energy pathways via beta-oxidation in the mitochondria:
  • Fatty acid chains are broken into 2-carbon units that form acetyl CoA unit by unit.
  • Many acetyl CoA units are produced, which then enter the TCA cycle.
  • Each cycle of beta-oxidation also yields NADH and FADH_2 to feed the electron transport chain.
  • Important caveat: Acetyl CoA produced from fatty acids cannot be used to make glucose.
  • Fat-derived energy feeding into the pathway:
  • Fatty acids → Acetyl CoA (via beta-oxidation).
  • Glycerol → pyruvate → acetyl CoA or glucose depending on energy needs.

• Amino acids as energy sources

  • Amino acids can be oxidized for energy if needed.
  • Entry points depend on amino acid type:
  • Some amino acids are glucogenic: converted to pyruvate or TCA cycle intermediates that can form glucose via gluconeogenesis.
  • Some amino acids are ketogenic: converted to acetyl CoA or acetoacetyl CoA, not used to form glucose.
  • Some amino acids enter directly into the TCA cycle at various points.
  • Deamination is required to remove the amino group before entry into energy pathways.
  • Deamination yields ammonia (NH_3):
  • Deamination reaction example: ext{R-CH(NH}2) ext{COOH} ightarrow ext{R-COOH} + NH3.
  • The body relies heavily on amino acids when glucose is lacking; fats alone are not a good source for glucose production.
  • There are more glucogenic than ketogenic amino acids, so protein can contribute to glucose formation when necessary.

• The TCA Cycle (Krebs) and its role in energy production

  • Location: mitochondria (inner membrane space in mitochondria).
  • Core cycle: oxaloacetate (4-carbon) combines with acetyl CoA (2-carbon) to form a 6-carbon compound (citrate) and proceeds through the cycle, releasing CO_2 and hydrogen atoms carried by coenzymes to the ETC.
  • Key inputs/outputs:
  • Acetyl CoA + Oxaloacetate → Citrate (6C) → CO2 release, generation of NADH and FADH2, and regeneration of oxaloacetate.
  • Role of coenzymes: Niacin (NAD^+) and riboflavin (FAD) carry hydrogens to the ETC as NADH and FADH_2.
  • After one turn, oxaloacetate is regenerated to continue the cycle with new Acetyl CoA.

• The Electron Transport Chain (ETC) and ATP synthesis

  • Location: inner mitochondrial membrane; chain of protein carriers that pass electrons along.
  • Electrons enter as part of NADH and FADH_2 produced by glycolysis, pyruvate oxidation, and the TCA cycle.
  • Electron transfer drives proton pumping across the membrane, creating a proton gradient.
  • The return flow of protons through ATP synthase drives the phosphorylation of ADP to ATP:
  • ADP + P_i
    ightarrow ATP
  • Water is formed when hydrogen ions combine with oxygen at the end of the chain.

• Energy yields and energy density of nutrients

  • Fat provides the most energy per gram: $9 ext{ kcal/g}$ (high carbon-hydrogen bond content).
  • Carbohydrates and proteins provide about $4 ext{ kcal/g}$ each.
  • Alcohol provides $7 ext{ kcal/g}$ but is considered a toxin and is metabolized differently; it contributes energy but does not support storage as efficiently as other fuels.
  • Fatty acid chains are not a good source of glucose; more acetyl CoA units are formed from fatty acids, yielding ATP, but not glucose.

• Feasting (fed state) vs. fasting transitions

  • Feasting (excess energy): metabolism favors fat formation from excess calories from any macronutrient; protein excess requires more energy to store (~25% of its calories go to storage); carbohydrates are generally stored as glycogen first and then as fat beyond energy needs.
  • The fuel mix in the body shifts depending on relative intake; with more protein or carbohydrate in the diet, fat usage for fuel decreases and fat storage increases if calories exceed needs.
  • Transition to fasting: after eating, glucose, glycerol, and fatty acids are used; excesses are stored; during fasting, glycogen and fat reserves are mobilized to produce acetyl CoA and ATP; basal metabolism uses roughly 65% of kcal needs.
  • The body cannot distinguish voluntary fasting from involuntary starvation; energy systems adapt to conserve energy as fasting continues.
  • Ketosis and appetite: prolonged fasting leads to use of fat to fuel the brain via ketone bodies, which slows protein breakdown and can induce appetite suppression.

• Feasting to fasting in more detail

  • Glucose, glycerol, and fatty acids are primary fuels after a meal; excess energy is stored as glycogen and fat.
  • When glycogen stores are full and energy intake remains high, excess energy is stored as fat in adipose tissue; fat storage is efficient.
  • Basal metabolism continues to require energy; the body adjusts to conserve energy during extended fasting.

• Low-carbohydrate diets: potential adverse effects

  • Common side effects: nausea, fatigue (especially with physical activity), constipation, low blood pressure.
  • Can disrupt acid-base balance (possible ketosis), increase uric acid (may affect kidney disease and joints), bad breath, and weight loss that is not necessarily fat loss.
  • Pregnancy considerations: potential fetal harm or stillbirth risk with very low carbohydrate intake.

• How the body metabolizes alcohol

  • Ethanol provides calories (7 kcal/g) but acts as a toxin; it can dissolve cell membranes and disrupt function.
  • Absorption: rapid on an empty stomach; slower with a meal.
  • Alcohol dehydrogenase (ADH) pathway: in stomach and liver; converts ethanol to acetaldehyde and then to acetyl CoA; some acetyl CoA enters the TCA cycle to yield energy, some is converted to fatty acids and stored as triglycerides.
  • MEOS (microsomal ethanol oxidizing system) pathway: becomes more active with chronic alcohol consumption and can affect drug metabolism.
  • Catalase pathway in the brain may contribute to some effects.
  • Excess alcohol tends to be stored as fat, particularly in the liver; chronic intake can lead to fatty liver and potentially cirrhosis.
  • The liver is the primary site of alcohol metabolism; fat becomes a preferred fuel when alcohol is present, reducing fatty acid oxidation for energy.

• The Cori cycle and fermentation byproducts

  • Lactate produced in muscles during anaerobic glycolysis is transported to the liver and converted back to glucose (Cori cycle).
  • This cycle helps sustain energy production during high-intensity activity when oxygen is limited.

• Summary of practical principles for exam focus

  • ATP is the energy currency; energy-yielding nutrients feed into glycolysis, beta-oxidation, and the TCA cycle, with NADH and FADH_2 delivering electrons to the ETC.
  • The fate of pyruvate depends on oxygen availability: aerobic pathways favor pyruvate oxidation to acetyl CoA; anaerobic pathways favor lactate formation with rapid ATP production.
  • Fat yields more energy per gram than carbohydrates or proteins, but cannot contribute to gluconeogenesis; glycerol can contribute to glycolysis and gluconeogenesis indirectly.
  • Amino acids enter energy pathways at multiple points; deamination is required to remove the amino group before entry; glucogenic amino acids can form glucose, while ketogenic amino acids form acetyl CoA or ketone bodies.
  • Alcohol metabolism introduces additional energy metabolism considerations and has distinct pathways (ADH, MEOS, catalase); excess alcohol energy is often stored as fat, particularly in the liver.
  • The body maintains energy balance through feeding/fasting transitions, glycogen storage, fat storage, and protein preservation (ketosis can modulate protein breakdown during extended fasting).

• Key equations and concepts to remember

  • Glycolysis (one glucose): ext{Glucose}
    ightarrow 2 ext{pyruvate} + 2 ext{NADH} + 2 ext{ATP (net)}
  • Pyruvate to Acetyl CoA (aerobic): ext{Pyruvate} + ext{CoA} + ext{NAD}^+
    ightarrow ext{Acetyl CoA} + CO_2 + ext{NADH}
  • Glucose to pyruvate in cytosol (glycolysis): ext{Glucose}
    ightarrow 2 ext{pyruvate}
  • ATP synthesis (general): ADP + P_i
    ightarrow ATP
  • Fat energy density: $9 ext{ kcal/g} ext{ fat}$
  • Alcohol energy density: $7 ext{ kcal/g}$

• Connections to broader principles

  • Energy metabolism integrates with nutrition, physiology, and health outcomes: overeating of any macronutrient can lead to fat storage; under-eating or fasting shifts metabolism toward glycogenolysis, lipolysis, gluconeogenesis, and ketosis.
  • Vitamin-derived coenzymes (NAD^+, FAD, etc.) are essential for energy pathways; deficiencies can halt metabolism and lead to disease states.
  • Real-world relevance: alcohol consumption metabolically shifts substrate use; low-carb diets alter energy substrates and can have side effects; understanding Cori cycle helps explain muscle endurance and fatigue during high-intensity efforts.