Metabolism and Bioenergetics: Key Concepts and Enzyme Regulation

Metabolism

sum of all chemical reactions in the body

Metabolic pathway

series of individual reactions that result in a final product

Bioenergetics

study of energy transfer in living organisms

Macronutrients

converted into usable energy in bioenergetics

ATP (Adenosine Triphosphate)

potential energy and energy currency of the cell

ATP's role

transfers free energy between catabolism and anabolism

Main purpose of ATP

supply energy for cellular work

Muscle contraction

increases ATP demand 500-1000 times

ATP levels

stay near resting levels (5-8 mmol/kg muscle ≈ 90 g total)

ATP storage

not stored and must be regenerated continuously

Catabolism

breakdown of energy-yielding nutrients

Catabolic reactions

release free energy in ATP, NADH, and FADH₂

Anabolism

uses ATP and reducing equivalents to build large molecules

First Law of Thermodynamics

energy cannot be created or destroyed only transformed

Forms of energy in the body

heat, light, mechanical, chemical, free energy, entropy

Entropy (S)

unusable energy or disorder

Free energy (ΔG)

usable energy that performs work

Second Law of Thermodynamics

energy transfer increases entropy

Exergonic reactions

energy releasing reactions

Endergonic reactions

energy requiring reactions

Reversibility

all reactions are reversible

Enthalpy (ΔH)

total energy transfer (heat + free energy)

Free Energy Equation

ΔG = ΔH - TΔS

Spontaneity

reactions must release free energy to occur spontaneously

Equilibrium constant (Keq)

ratio of products to substrates

Standard free energy equation

ΔG°′ = -RT lnKeq

Actual free energy equation

ΔG = ΔG°′ + RT lnL (L = mass-action ratio)

ATP hydrolysis ΔG°′

-7.3 kcal/mol

Physiological ΔG for ATP

about -14 kcal/mol

Exergonic reaction

releases free energy (e.g., ATP breakdown)

Endergonic reaction

requires energy (e.g., biosynthesis, contraction)

Coupled reactions

endergonic and exergonic reactions linked together

Coupled reaction example

glucose + Pi → G6P (+4.3 kcal/mol) and ATP → ADP + Pi (-7.3 kcal/mol)

Net energy of coupled reaction

-3.0 kcal/mol (spontaneous)

Oxidation

removal or loss of electrons

Reduction

gain of electrons

Redox reactions

always paired (one oxidized, one reduced)

Electron carriers

NAD⁺/NADH and FAD/FADH₂

Pyruvate reduction example

pyruvate reduced to lactate

Lactate production role

consumes protons and acts as a buffer to slow acidification

Enzymes

biological catalysts that lower activation energy

Free energy and enzymes

enzymes do not alter free energy release

Metabolic regulation

controlled by enzyme activity

Enzyme concentration

increases or decreases reaction rate

Michaelis-Menten kinetics

relationship between reaction rate and substrate concentration

V

velocity or rate of reaction

Vmax

maximum rate of reaction when enzyme is saturated

Km

substrate concentration when reaction is half Vmax

Activation effect

increases Vmax, decreases Km (faster and higher affinity)

Inhibition effect

decreases Vmax, increases Km (slower and lower affinity)

Substrate concentration

higher substrate = faster reaction rate until saturation

Equilibrium enzymes

activity determined by substrate/product concentration (e.g., creatine kinase)

Allosteric enzymes

regulated by activators or inhibitors (e.g., PFK, phosphorylase)

Allosteric enzyme locations

at pathway starts, branches, and ATP-use sites

Factors affecting enzyme rate

enzyme concentration, substrate, temperature, pH, regulation

Phosphagen system

fastest system for ATP regeneration

Creatine kinase (CK)

catalyzes ADP + CrP ⇌ ATP + Cr

Adenylate kinase (ADK)

catalyzes ADP + ADP ⇌ ATP + AMP

Equilibrium reactions

reactions where direction and rate are determined by substrates and products

Delta G at rest in phosphagen system

theoretically 0

Directionality of equilibrium reactions

determined by substrate and product concentrations

Non-allosteric enzymes

responsive to substrate/product concentrations

Adenylate kinase reaction

Maintains energy homeostasis in cell and regenerates AMP

AMP

Used as a signaling molecule for energy status

Adenylate charge

Index that measures energy state in a cell

Low adenylate charge

Indicates fatigue

Purine nucleotide cycle

Maintains adenylate charge by lowering AMP

Creatine kinase reaction

Most immediate means to regenerate ATP

Phosphagen system stores

24-26 mmol/kg wet muscle of CrP

Creatine kinase location

Near contractile proteins, outer mitochondrial membrane, cytoplasm (~80%)

Creatine phosphate shuttle

Transfers phosphate from mitochondrial ATP to cytosolic Cr

Creatine phosphate shuttle purpose

Ensures rapid ATP supply at muscle

Mitochondrial CK enzyme

Produces mitochondrial ADP and cytosolic CrP

High mitochondrial CK activity

Increases ADP and stimulates mitochondrial respiration

Acidosis recovery

Slower after extreme acidosis than minimal

Acidosis recovery time

2-3 minutes is ~90th percentile for minimal acidosis

Phosphagen system positives

Associated with higher AMP, Pi, and ADP

CK reaction and H+

CK consumes a proton (H+)

Phosphagen system negatives

Decrease in adenylate ratios and CrP levels

Low CrP and ATP

Results in higher ADP and AMP

High AMP levels

Lead to higher NH4+ in cell

Glycolysis location

Cytosol

Main role of glycolysis

Degrade glucose/glycogen into pyruvate

Other roles of glycolysis

Regenerate ATP and produce NADH + H⁺

Importance of glycogenolysis

Provides rapid G6P production

Phosphorylase

Removes α-1,4 linked glucose molecules from glycogen

Phosphorylase forms

Active (a) and inactive (b)

Phosphorylase activators

Glucagon, epinephrine, cAMP, AMP, Ca²⁺, Pi

Phosphorylase inhibitors

Insulin

Hexokinase inhibition

Inhibited by G6P accumulation

Kinase

Enzyme that adds or transfers phosphate groups

Mutase

Enzyme that alters position of a side group within same molecule

Transferase

Enzyme that transfers side group from one molecule to another

Isomerase

Enzyme that alters molecular shape

PFK (phosphofructokinase)

Rate-limiting enzyme of glycolysis

PFK activator

AMP

PFK inhibitors

ATP, H+, and citrate

Lyase

Enzyme that cleaves bonds and leaves a double bond

Glyceraldehyde 3-phosphate dehydrogenase

Releases NADH (electron carrier)

NADH function

Electron carrier to mitochondria