Cellular Metabolism and the Mechanisms of Cellular Respiration

Principles of Metabolism: Anabolism vs. Catabolism

• Metabolism within a cell occurs within the plasma membrane and is categorized into two primary types of reactions: anabolism and catabolism.

• Anabolism involves growth and building up reactions that create larger molecules from smaller components.

• Catabolism involves reactions that break down larger molecules into smaller ones.

• Anabolic and catabolic reactions are interdependent; catabolic reactions provide the drive for anabolic reactions, and vice versa. It is effectively impossible to have one without the other.

• In a healthy adult, anabolic and catabolic reactions should ideally be in balance or "in sync."

  • If anabolic reactions outpace catabolic reactions: There is a gain in body mass. While adults do not grow taller after puberty, they can grow wider.
  • If catabolic reactions outpace anabolic reactions: There is a continual loss of body weight.

• During childhood and adolescence, it is necessary for anabolic reactions to outpace catabolic reactions. This allows for growth in length (height) and width (body mass), often referred to as "filling out."

Anabolic Reactions and Dehydration Synthesis

• Anabolic reactions are often referred to as dehydration synthesis reactions because they involve pulling a water molecule out to form a bond.

• Metabolic water is the term for the water formed during these anabolic processes.

• Examples of anabolic storage and synthesis include:

  • Carbohydrates: Glucose molecules are linked to form polysaccharides and eventually glycogen. Critical storage sites include the liver and skeletal muscle.
  • Fats: Three fatty acids are combined with glycerol to form triglycerides, which are stored in adipose tissue (fat cells).
  • Proteins: Amino acids are strung together into polypeptides. Once these chains are large enough, they are classified as proteins. Storage occurs in skeletal muscle, the liver, and the blood plasma (where they are known as plasma proteins).

• Reduction reactions are also considered anabolic. In this context, reduction is defined by the acronym RIG: Reduction Is Gain. Specifically, it is a gain of hydrogens ($H$), though it also technically involves a gain of electrons and hydrogen ions ($H^+$).

Catabolic Reactions, Hydrolysis, and Redox

• Catabolic reactions are often referred to as hydrolysis reactions. These involve adding water to a molecule to cleave or break the bonds between component molecules.

• Examples of catabolic breakdown include:

  • Glycogen: Broken down into glucose, occurring primarily in the liver and skeletal muscle.
  • Triglycerides: Broken down into fatty acids, monoglycerides, and glycerol.
  • Proteins: Broken down into their constituent amino acids.

• Oxidation reactions are considered catabolic. In this context, oxidation is defined by the acronym OIL: Oxidation Is Loss. This refers to the loss of hydrogens ($H$).

• Redox (Reduction-Oxidation) Reactions: Whenever a molecule is oxidized (loses hydrogens), those hydrogens must go somewhere else. Consequently, another molecule is reduced (gains hydrogens). These paired processes are essential for cellular energy transfer.

Fuel Sources for ATP Generation

• Cells utilize various fuel sources to generate Adenosine Triphosphate ($ATP$).

• Primary Fuel: Glucose, derived from the breakdown of glycogen (carbohydrates).

• Secondary Fuel: Fats, specifically triglycerides broken down into fatty acids and glycerol. Fatty acids are the more significant primary energy contributor among the two lipid components. Glucose and fatty acids are utilized daily.

• Tertiary/Last Resort Fuel: Proteins (amino acids). While some proteins may be used daily, they are the least likely to be used for fuel. They are prioritized only during long intervals between meals, fasting, or starvation.

Overview of Cellular Respiration

• Cellular respiration consists of four major steps:

  1. Glycolysis
  2. Formation of Acetyl Coenzyme A (also known as the "prep step")
  3. The Krebs Cycle (also known as the Citric Acid Cycle)
  4. The Electron Transport Chain ($ETC$)

• Anaerobic Respiration: Glycolysis is the only anaerobic part of the chain, meaning it can generate $ATP$ without oxygen. However, it only generates a small amount of $ATP$ and produces byproducts that lead to fatigue, making it unsustainable for prolonged activity.

• Aerobic Respiration: The steps following glycolysis—the formation of Acetyl Coenzyme A, the Citric Acid Cycle, and the Electron Transport Chain—all require oxygen to function.

• The general chemical formula for cellular respiration is:     $C_6H_{12}O_6 + 6\,O_2 \rightarrow 6\,CO_2 + 6\,H_2O + \text{ATP} + \text{Heat}$

• One glucose molecule ($C_6H_{12}O_6$) is oxidized into six molecules of carbon dioxide ($6\,CO_2$). Six oxygen molecules ($6\,O_2$) are reduced into six water molecules ($6\,H_2O$).

• Energy Efficiency and Heat: During the production and utilization of $ATP$, a significant portion of energy is lost as heat. This process accounts for the high internal body temperature of nearly $100\,\text{degrees}$.

Detailed Steps of the Cellular Respiration Pathway

• Glycolysis: One glucose molecule (a $6$-carbon sugar) undergoes enzymatic reactions in the cell cytoplasm to produce two molecules of pyruvate (or pyruvic acid, a $3$-carbon molecule).

  • Net yield from glycolysis: $2\,ATP$ and $2\,NADH$.
  • $NADH$ is a carrier molecule derived from the B vitamin niacin (coenzyme).

• Anaerobic Conditions (Lactic Acid Pathway): In the absence of sufficient oxygen (e.g., during a $100\text{-meter}$ sprint), pyruvate is converted into lactate (lactic acid).

  • Lactate causes muscle fatigue, a drop in $pH$, and an oxygen debt characterized by a burning sensation, heavy limbs, and deep gasping for air.
  • This is a reversible reaction. When oxygen becomes available, lactate is converted back into pyruvate.
  • The liver can also pick up lactate from the blood and convert it back into pyruvate and then glucose for release into the blood.

• The Prep Step (Formation of Acetyl Coenzyme A): In the presence of oxygen, pyruvate enters the mitochondria. Two carbons are removed to create two molecules of Acetyl Coenzyme A (Acetyl CoA).

  • Yield: $2\,CO_2$ and $2\,NADH$.
  • The B vitamin pantothenic acid is essential for the creation of Acetyl CoA.

• The Citric Acid Cycle (Krebs Cycle): Acetyl CoA enters this cycle within the mitochondria. Because there are two molecules of Acetyl CoA per original glucose, the cycle turns twice.

  • Total yield for two turns: $2\,ATP$, $4\,CO_2$, $6\,NADH$, and $2\,FADH$.
  • $FADH$ is a carrier molecule derived from the B vitamin riboflavin.

• Cumulative Totals prior to the ETC:

  • $10\,NADH$ ($2$ from glycolysis, $2$ from the prep step, $6$ from the Citric Acid Cycle).
  • $2\,FADH$
  • $4\,ATP$ ($2$ from glycolysis, $2$ from the Citric Acid Cycle).

The Electron Transport Chain and ATP Synthase

• The Electron Transport Chain ($ETC$) is located along the inner membrane of the mitochondria.

• Mechanism of Energy Transfer:

  • $NADH$ and $FADH$ transport hydrogens to the $ETC$ and drop them off.
  • Proteins in the $ETC$ pump hydrogen ions ($H^+$) from the inner mitochondrial space into the outer mitochondrial space (the space between the inner and outer membranes).
  • This creates a high concentration gradient of $H^+$ ions in the outer space.

• ATP Synthase: Hydrogen ions diffuse down their concentration gradient back into the inner space through a specific protein known as ATP synthase.

  • ATP synthase functions like a water mill; the kinetic energy of the flowing hydrogen ions is used to attach a phosphate group to Adenosine Diphosphate ($ADP$) to generate $ATP$.

• Final Electron Acceptor: To prevent the $pH$ from dropping due to excess hydrogen, two hydrogen ions combine with an oxygen molecule to generate $H_2O$ (metabolic water).

• Test-Based ATP Yields:

  • $1\,NADH = 3\,ATP$
  • $1\,FADH = 2\,ATP$
  • The maximum amount of $ATP$ generated from the entire cellular respiration process for one glucose molecule is $38\,ATP$.