24.1 Overview of Metabolic Reactions

Metabolic Reactions

Metabolic reactions are how your cells transform nutrients into usable energy and structural building blocks. Every process in the body, from muscle contraction to cell division, depends on these reactions. They fall into two broad categories: catabolic reactions that break things down and anabolic reactions that build things up, with ATP serving as the energy currency that links the two.

Breakdown of Polymers to Monomers

Catabolic reactions break complex molecules into simpler ones through hydrolysis, a process that uses water to cleave bonds between monomers. Specific enzymes catalyze each hydrolysis reaction, dramatically increasing the rate at which bonds are broken.

The major polymers broken down this way include:

• Polysaccharides (starch, glycogen) → glucose
• Proteins → amino acids
• Triglycerides → fatty acids and glycerol

Once released, these monomers can be used for energy or recycled as raw materials for anabolic reactions:

• Glucose enters glycolysis and eventually the citric acid cycle to produce ATP
• Amino acids can be used to build new proteins, or converted to glucose or fatty acids when needed
• Fatty acids undergo beta-oxidation, which chops them into acetyl-CoA units that feed into the citric acid cycle

Formation of Polymers from Monomers

Anabolic reactions do the opposite of catabolism. They construct complex molecules from simpler ones through dehydration synthesis (also called condensation), which removes a water molecule to form a covalent bond between monomers. Like hydrolysis, these reactions are enzyme-catalyzed.

Anabolic reactions require energy input, typically from ATP, to drive bond formation. Key examples include:

• Glucose → glycogen: Glucose monomers are linked together and stored as glycogen in liver and skeletal muscle
• Amino acids → proteins: Amino acids are joined into polypeptide chains that fold into functional proteins
• Fatty acids + glycerol → triglycerides: These are assembled for long-term energy storage in adipose tissue

ATP as Metabolic Energy Currency

ATP (adenosine triphosphate) is the primary energy currency of the cell. It consists of an adenosine molecule bonded to three phosphate groups. The bond between the second and third phosphate is relatively unstable, which is why breaking it releases usable energy.

When the terminal phosphate is hydrolyzed, ATP becomes ADP (adenosine diphosphate) plus inorganic phosphate:

$ATP + H_2O \rightarrow ADP + P_i + Energy$

This released energy powers processes that wouldn't happen on their own (endergonic reactions):

• Anabolic reactions like protein synthesis and glycogen synthesis
• Active transport of molecules against their concentration gradients across cell membranes
• Mechanical work like muscle contraction

ATP is constantly regenerated from ADP and $P_i$:

$ADP + P_i + Energy \rightarrow ATP$

This regeneration happens through two mechanisms:

1. Substrate-level phosphorylation: Direct transfer of a phosphate group to ADP, occurring during glycolysis and the citric acid cycle
2. Oxidative phosphorylation: Uses the electron transport chain in mitochondria to produce the vast majority of ATP (about 90% of total ATP yield)

Cellular Metabolism

Oxidation-Reduction in Cellular Metabolism

Redox reactions are the electron-transfer events that drive energy production in cells. Oxidation is the loss of electrons; reduction is the gain of electrons. These always occur together, because when one molecule loses electrons, another must accept them.

Two key electron carriers shuttle these electrons through metabolic pathways:

• $NAD^+$ accepts electrons to become NADH
• $FAD$ accepts electrons to become $FADH_2$

In catabolic pathways (glycolysis, citric acid cycle), nutrients are progressively oxidized, and the electrons they lose are picked up by $NAD^+$ and $FAD$. Then, in the electron transport chain, NADH and $FADH_2$ donate those electrons to create a proton gradient across the inner mitochondrial membrane. That gradient drives ATP synthase to produce ATP through oxidative phosphorylation.

Redox chemistry also matters for anabolism. Biosynthetic pathways like fatty acid synthesis and amino acid synthesis require reducing power, supplied mainly by NADPH (the phosphorylated cousin of NADH). NADPH donates electrons to build these molecules rather than to make ATP.

Hormones in Metabolic Regulation

Hormones act as signals that shift the body's metabolism between building up (anabolic) and breaking down (catabolic) states, depending on conditions like feeding, fasting, or stress.

Insulin (from pancreatic beta cells) is the major anabolic hormone:

• Stimulates glucose uptake by muscle and adipose tissue
• Promotes glycogen synthesis and lipogenesis (fat building)
• Enhances protein synthesis and inhibits protein breakdown

Glucagon (from pancreatic alpha cells) is the major catabolic hormone and opposes insulin:

• Stimulates glycogenolysis (glycogen breakdown) and gluconeogenesis (making glucose from non-carbohydrate sources) in the liver
• Promotes lipolysis (triglyceride breakdown) in adipose tissue, releasing fatty acids into the blood

Cortisol (from the adrenal cortex) is a catabolic stress hormone:

• Stimulates proteolysis (protein breakdown) in muscle, freeing amino acids for gluconeogenesis
• Enhances lipolysis and gluconeogenesis to ensure glucose is available during prolonged stress

Growth hormone (GH) (from the anterior pituitary) has mixed effects but is primarily anabolic:

• Stimulates protein synthesis and muscle growth
• Promotes lipolysis, mobilizing fatty acids for fuel
• Antagonizes insulin's action, reducing glucose uptake by tissues (this spares glucose for the brain)

Metabolic Regulation and Control

Metabolic pathways are interconnected chains of chemical reactions, and the body has several mechanisms to speed them up or slow them down as needed.

Enzymes are protein catalysts that dramatically increase reaction rates without being consumed. Many enzymes require coenzymes, which are non-protein organic molecules (often derived from vitamins) that assist in catalysis by carrying chemical groups or electrons between reactions.

Two important regulatory mechanisms keep pathways in check:

• Feedback inhibition: The end product of a pathway inhibits an enzyme at an earlier step. This prevents overproduction. For example, if a cell has plenty of a particular amino acid, that amino acid can shut down the first enzyme in its own synthesis pathway.
• Allosteric regulation: Molecules bind to a site on the enzyme other than the active site, changing the enzyme's shape and either increasing or decreasing its activity. This allows the cell to fine-tune reaction rates in response to changing conditions.