METABOLISM
Metabolism
Metabolism is the sum total of all chemical reactions
occurring within a living organism to sustain life.
These chemical processes are necessary for growth,
reproduction, repair, and response to environmental
changes.
Why is Metabolism
Important?
Metabolism is essential for life
because it supports key cellular
functions that keep organisms alive
and functioning. Below are the major
roles of metabolism:
Why is Metabolism
Important?
A. OBTAINING ENERGY FROM NUTRIENTS
•Living organisms need energy to perform biological functions
such as movement, transport, and synthesis.
•Energy is obtained from nutrients like carbohydrates, fats, and
proteins through catabolic reactions.
•Example:
•During cellular respiration, glucose is broken down into carbon
dioxide and water, releasing energy that is stored in ATP
(adenosine triphosphate).
Why is Metabolism
Important?
B. PRODUCING CELLULAR COMPONENTS
•Cells need to synthesize important macromolecules such as:
• Proteins: Enzymes, structural components, and signaling molecules.
• Lipids: Components of cell membranes and energy storage molecules.
• Nucleic Acids: DNA and RNA, which are critical for genetic information and
protein synthesis.
•These processes are anabolic and require energy input, often derived from ATP.
Example:
•Protein synthesis: Amino acids are linked together in a specific sequence to
form proteins, driven by energy from ATP.
Why is Metabolism
Important?
MAINTAINING HOMEOSTASIS
•Homeostasis refers to the ability of an organism to maintain a stable
internal environment despite changes in external conditions.
•Metabolism helps regulate:
•Energy balance: Matching energy production with energy consumption.
•Nutrient levels: Ensuring the proper concentration of glucose, amino
acids, and ions.
•Waste removal: Metabolic processes help break down toxins and
remove waste products (e.g., urea production in humans).
Metabolism
1.Metabolism consists of two main types of processes:
2.Catabolism: Reactions that break down complex
molecules (like carbohydrates, lipids, and proteins)
into simpler ones, releasing energy.
3.Anabolism: Reactions that build complex molecules
(such as proteins, DNA, or lipids) from simpler ones,
requiring energy.
Metabolism
Catabolic processes act like workers breaking down
raw materials to release energy (e.g., dismantling
glucose for ATP production).
Anabolic processes act like assembly lines that use the
energy to build new products (e.g., producing proteins
from amino acids).
These processes are interconnected, as energy released during catabolic
reactions is often used to fuel anabolic reactions. Together, they maintain the
energy balance and functionality of the cell.
Catabolism: Breaking Down Molecules
Catabolism refers to the chemical reactions that break down complex molecules into
simpler ones, releasing stored energy that can be used by the cell.
Key Characteristics of Catabolism:
•Purpose:
• To release energy stored in the chemical bonds of macromolecules (carbohydrates, lipids,
and proteins).
• To generate ATP, the energy currency of the cell.
•Energy Flow:
• Catabolic reactions are exergonic (release energy).
•Products:
• Simpler molecules (e.g., CO₂, H₂O, NH₃).
• ATP and other high-energy molecules (e.g., NADH, FADH₂).
•Enzymes:
• Specialized enzymes catalyze each step of a catabolic pathway.
• Example: Amylase breaks down starch into glucose.
Catabolism: Breaking Down Molecules
Examples of Catabolic Pathways:
1.Cellular Respiration:
1. Glucose is broken down into CO₂ and H₂O to generate ATP
2.Steps of Cellular Respiration:
1. Glycolysis: Breakdown of glucose into pyruvate.
2. Krebs Cycle: Oxidation of acetyl-CoA into CO₂, producing NADH and FADH₂.
3. Electron Transport Chain: Generates ATP using energy from NADH and FADH₂.
3.Lipid Breakdown:
1. Beta-oxidation breaks down fatty acids into acetyl-CoA units, which enter the Krebs
cycle.
4.Protein Catabolism:
1. Proteins are broken down into amino acids, which are further deaminated to produce
energy.
Anabolism: Building Molecules
Anabolism refers to the set of chemical reactions that construct complex
molecules from simpler ones, requiring energy input.
Key Characteristics of Anabolism:
•Purpose:
• To synthesize macromolecules needed for growth, repair, and cellular
functions.
•Energy Flow:
• Anabolic reactions are endergonic (require energy).
• Energy is provided by ATP and high-energy molecules like NADPH.
•Products:
• Complex molecules (e.g., proteins, DNA, lipids, glycogen).
•Enzymes:
• Specific enzymes catalyze anabolic reactions.
• Example: DNA polymerase helps synthesize DNA strands.
Anabolism: Building Molecules
Examples of Anabolic Pathways:
1.Protein Synthesis:
1. Amino acids are linked together by peptide bonds to form proteins during
translation.
2. Requires ATP and the ribosome machinery.
2.DNA Replication:
1. Nucleotides are assembled into DNA strands using enzymes like DNA
polymerase.
3.Photosynthesis:
1. In plants, CO₂ and water are converted into glucose using light energy.
4.Glycogen Synthesis:
1. Glucose molecules are linked together to form glycogen, the storage form of
glucose.
Interconnection of Catabolism and Anabolism
Catabolism and anabolism are not isolated processes but are interconnected:
•Energy Coupling:
• Energy released by catabolic reactions is stored in molecules like ATP and
NADH, which are then used to drive anabolic reactions.
•Recycling of Molecules:
• Catabolic pathways break down macromolecules into precursors (e.g., amino
acids, glucose) that anabolic pathways use to synthesize new
macromolecules.
Example:
•During exercise, muscles break down glucose (catabolism) to produce ATP, which
is then used to repair and grow muscle tissue (anabolism).
ATP
ATP (Adenosine Triphosphate) is the primary energy currency of the cell.
It stores and transfers energy for various biological processes, acting like a
rechargeable battery for cellular functions.
Structure of ATP:
•Adenosine: Made of adenine (a nitrogenous base) and ribose (a five-carbon
sugar).
•Three Phosphate Groups: Linked by high-energy bonds. The energy is stored in
the bonds between these phosphate groups, particularly the last two.
When one phosphate group is removed from ATP, it becomes ADP (Adenosine
Diphosphate), and energy is released for cellular activities.
Why is ATP Important in Metabolism?
ATP is central to metabolism because it provides the energy required for
cellular processes, including:
1.Biosynthesis (Anabolism): Building macromolecules like proteins, nucleic
acids, and lipids.
2.Active Transport: Moving molecules against their concentration gradients
(e.g., Na⁺/K⁺ pump).
3.Mechanical Work: Muscle contraction, cilia movement, and intracellular
transport.
4.Signal Transduction: Driving cellular responses through phosphorylation
events.
Why is ATP Important in Metabolism?
How Does ATP Store and Release Energy?
The phosphate bonds in ATP are rich in energy due to the electrostatic
repulsion between negatively charged phosphate groups.
1.Hydrolysis of ATP:
1. ATP releases energy when the terminal phosphate bond is broken.
2. This reaction produces ADP (Adenosine Diphosphate) and an inorganic
phosphate.
2.Regeneration of ATP:
•ATP is replenished from ADP using energy from catabolic reactions (e.g.,
cellular respiration).
•Example: In oxidative phosphorylation, the energy released from electron
transport drives ATP synthesis.
Why is ATP Important in Metabolism?
Energy coupling refers to the process where ATP links exergonic (energy-
releasing) and endergonic (energy-requiring) reactions.
Key Features:
1.Exergonic Reactions (Catabolism):
1. ATP is generated when energy is released by breaking down molecules
(e.g., glucose, fatty acids).
2. Example: During glycolysis, ATP is produced as glucose is broken down.
2.Endergonic Reactions (Anabolism):
1. ATP provides the energy needed to build molecules or perform cellular
work.
2. Example: ATP powers the synthesis of proteins from amino acids.
What Are Metabolic Pathways?
Metabolic pathways are a series of interconnected chemical reactions that occur
within a cell. Each step is catalyzed by a specific enzyme, ensuring precise control
and efficiency.
•Linear Pathways: Sequential steps from a starting molecule to a final product.
• Example: Glycolysis.
•Cyclic Pathways: Reactions regenerate a starting molecule at the end of the
cycle.
• Example: Krebs cycle.
•Branched Pathways: Pathways split into multiple directions, leading to different
products.
• Example: Amino acid biosynthesis.
What Are Metabolic Pathways?
Key Regulatory Mechanisms:
1.Feedback Inhibition:
1. The end product of a pathway inhibits an earlier step.
2. Example: ATP inhibits phosphofructokinase in glycolysis.
2.Allosteric Regulation:
1. Enzyme activity is modulated by molecules that bind to sites other than the active site.
2. Example: AMP activates glycolysis by enhancing enzyme activity when energy is low.
3.Covalent Modifications:
1. Enzymes are activated or deactivated by phosphorylation or other chemical changes.
2. Example: Insulin triggers phosphorylation events to activate glycogenesis.
4.Hormonal Control:
1. Hormones like insulin and glucagon adjust pathways based on energy needs.
2. Example: Insulin stimulates glucose uptake and glycolysis.
Redox Reactions in Metabolism
Redox reactions, or reduction-oxidation reactions, are fundamental to cellular metabolism.
They involve the transfer of electrons from one molecule to another, playing a central role in
energy generation and biosynthesis. These reactions form the basis of processes like cellular
respiration and photosynthesis, allowing organisms to harness and store energy in usable forms.
What Happens in a Redox Reaction?
•Oxidation: The loss of electrons by a molecule, atom, or ion.
•Reduction: The gain of electrons by a molecule, atom, or ion.
These two processes are always coupled, as one molecule donates
electrons (oxidized) while another accepts them (reduced).
Redox Reactions in Metabolism
Why Are Redox Reactions Important in Metabolism?
The transfer of electrons in redox reactions releases energy stored in
chemical bonds. This energy is used to:
•Produce ATP, the energy currency of the cell.
•Drive anabolic reactions that build macromolecules.
•Maintain ion gradients across membranes for cellular functions like
active transport and nerve signaling.
Components of Redox Reactions in Cells
A. Electron Donors and Acceptors
•Electron Donors: Molecules that lose electrons and are oxidized (e.g., glucose, NADH).
•Electron Acceptors: Molecules that gain electrons and are reduced (e.g., oxygen, NAD⁺)
B. Electron Carriers
Specialized molecules shuttle electrons between reactions, allowing energy transfer without damaging the
cell.
•NAD⁺/NADH (Nicotinamide Adenine Dinucleotide):
• NAD⁺ accepts electrons and becomes reduced to NADH.
• NADH later donates electrons in processes like oxidative phosphorylation.
•FAD/FADH₂ (Flavin Adenine Dinucleotide):
• FAD is reduced to FADH₂ during the Krebs cycle.
• FADH₂ transfers electrons to the electron transport chain.
C. The Electron Transport Chain (ETC)
•A series of protein complexes in the inner mitochondrial membrane where redox reactions occur in
sequence.
•Electrons from NADH and FADH₂ are passed along the chain, releasing energy to pump protons (H⁺) across
the membrane, creating an electrochemical gradient.
•This gradient drives ATP synthesis via ATP synthase.
Examples of Redox Reactions in Metabolism
A. Glycolysis
•Glucose is partially oxidized to form pyruvate.
•NAD⁺ is reduced to NADH in the process, capturing energy.
B. Krebs Cycle (Citric Acid Cycle)
•Acetyl-CoA is oxidized to CO₂.
•NAD⁺ and FAD are reduced to NADH and FADH₂, storing high-energy electrons for the ETC.
C. Oxidative Phosphorylation
•NADH and FADH₂ donate electrons to the ETC.
•Oxygen acts as the final electron acceptor, being reduced to water.
•The energy released during these redox reactions is used to generate ATP.
D. Photosynthesis
•During the light-dependent reactions, water is oxidized to oxygen, and electrons are
transferred to NADP⁺, reducing it to NADPH.
•NADPH is then used in the Calvin cycle for carbon fixation.
Redox Imbalances and Pathological Implications
Disruptions in redox reactions can lead to metabolic disorders and
oxidative stress:
•Oxidative Stress: Excess ROS, caused by imbalanced redox
reactions, damages DNA, proteins, and lipids.
• Linked to diseases like cancer, diabetes, and
neurodegenerative disorders.
•Mitochondrial Dysfunction: Faulty electron transport can lead to
insufficient ATP production.
• Associated with aging and metabolic syndromes.
Laboratory Techniques to Reconstruct Cellular
Metabolism
Metabolomics
Metabolomics is the large-scale study of small molecules,
known as metabolites, within a biological system.
•Technique: HPLC, Mass spectrometry (MS) and nuclear
magnetic resonance (NMR) spectroscopy are widely used
to identify and quantify metabolites.
•Applications: Provides a snapshot of the metabolic state,
helping to map pathways and detect metabolic changes.
Laboratory Techniques to Reconstruct Cellular
Metabolism
Isotopic Tracing
This technique uses isotopically labeled molecules (e.g., carbon-13
or nitrogen-15) to track the flow of atoms through metabolic
pathways.
•Technique:
• Cells are fed labeled substrates (e.g., ¹³C-glucose).
• The distribution of isotopes in downstream metabolites is
measured using MS or NMR.
•Applications: Identifies pathway fluxes and branching points,
helping to reconstruct metabolic routes.
Laboratory Techniques to Reconstruct Cellular
Metabolism
Enzyme Kinetics and Activity Assays
Understanding how enzymes catalyze reactions is essential for
reconstructing metabolism.
•Technique:
• Purified enzymes are studied in vitro using
spectrophotometry or fluorometry to measure reaction rates.
• Michaelis-Menten kinetics are used to quantify enzyme
efficiency.
•Applications: Defines the role of specific enzymes in metabolic
pathways.
Laboratory Techniques to Reconstruct Cellular
Metabolism
CRISPR-Cas9 and Genetic Engineering
Genetic tools are used to manipulate metabolic pathways directly.
•Technique:
• Gene knockouts or overexpression to study the role of specific enzymes.
• Use of CRISPR to edit metabolic genes in living cells.
•Applications: Determines pathway contributions and reconstructs synthetic
metabolic networks.
Laboratory Techniques to Reconstruct Cellular
Metabolism
Proteomics
Proteomics studies the entire set of proteins involved in metabolism.
•Technique:
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify
and quantify enzymes.
• Stable isotope labeling of amino acids in cell culture (SILAC) for dynamic
studies.
•Applications: Maps which enzymes are present and active in metabolic
pathways.
Overview of Glycolysis
Glycolysis is a fundamental metabolic pathway that breaks down glucose, a six-carbon sugar, into
two molecules of pyruvate, a three-carbon compound.
This process occurs in the cytoplasm of cells and is the first step in cellular respiration.
For each molecule of glucose, glycolysis
generates:
•2 ATP (net gain: 4 produced - 2 consumed)
•2 NADH (electron carriers)
•2 Pyruvate
Overview of Glycolysis
Biological Importance of Glycolysis
Energy Production:
•Glycolysis is a primary energy-producing pathway, especially in cells that lack mitochondria
(e.g., red blood cells) or under anaerobic conditions (e.g., during intense exercise).
•It provides ATP quickly, which is crucial for cells with high energy demands, such as muscle
cells.
Metabolic Intermediates:
•Glycolysis generates intermediates like glucose-6-phosphate and fructose-6-
phosphate, which are used in other metabolic pathways, including the pentose
phosphate pathway and amino acid synthesis.
Biosynthesis:
•Intermediates from glycolysis are precursors for synthesizing nucleotides, lipids, and amino
acids, supporting cell growth and repair.
•For example, dihydroxyacetone phosphate (DHAP) is critical in triglyceride synthesis.
Overview of Glycolysis
Pathologies Associated with Glycolysis
Cancer Metabolism (Warburg Effect):
•Many cancer cells rely heavily on glycolysis for energy production, even in the presence of
oxygen, a phenomenon known as the Warburg effect.
•This reliance on glycolysis supports rapid cell proliferation but also creates vulnerabilities
that can be targeted therapeutically, such as inhibiting glycolytic enzymes (e.g., hexokinase
or pyruvate kinase).
Diabetes Mellitus:
•Dysregulated glucose metabolism in diabetes impacts glycolysis. For example, in
hyperglycemia, excessive glycolytic activity in tissues can lead to harmful byproducts that
damage cells, contributing to complications like neuropathy and retinopathy.
Overview of Glycolysis
Pathologies Associated with Glycolysis
•Genetic Disorders:
•Pyruvate Kinase Deficiency: A genetic mutation in pyruvate kinase, a key glycolytic enzyme,
leads to hemolytic anemia due to reduced ATP production in red blood cells.
•Phosphofructokinase Deficiency (Glycogen Storage Disease Type VII): Impairs glycolysis in
muscle cells, causing exercise intolerance and muscle weakness.
•Neurodegenerative Diseases:
•Impaired glycolysis has been implicated in conditions like Alzheimer’s disease, where reduced
glucose metabolism in the brain correlates with cognitive decline.
Overview of Krebs Cycle
The Krebs cycle, also known as the citric acid cycle or tricarboxylic acid
(TCA) cycle, is a central metabolic pathway in aerobic respiration.
It takes place in the mitochondrial matrix and plays a key role in energy
production and biosynthesis.
•Oxidizes acetyl-CoA, a two-carbon molecule derived
from carbohydrates, fats, and proteins, to produce
energy-rich molecules (NADH, FADH2) and CO2.
•Provides intermediates for biosynthetic processes.
The NADH and FADH2 generated transfer their electrons to
the electron transport chain, driving oxidative
phosphorylation to produce ATP!!!!!!!!!!
Overview of Krebs Cycle
Pathologies Associated with Krebs Cycle
•Metabolic Disorders:
•Mutations in TCA cycle enzymes can lead to rare diseases, such as fumarase deficiency,
characterized by severe neurological impairments.
•Defects in the cycle can also contribute to certain cancers due to altered metabolic states in
tumor cells.
•Role in Cancer (Oncometabolites):
•Abnormal activity of TCA cycle enzymes (e.g., succinate dehydrogenase or fumarase) can
lead to the accumulation of oncometabolites, which promote tumorigenesis.
Overview of Krebs Cycle
Pathologies Associated with Krebs Cycle
Mitochondrial Diseases:
•Dysfunction of the TCA cycle due to mitochondrial abnormalities can impair
energy production, leading to a range of conditions, including myopathies and
neurodegenerative diseases.
Overview of the Electron Transport Chain (ETC)
The electron transport chain (ETC) is the final stage of cellular respiration, where most of
the ATP in aerobic organisms is produced. It occurs in the inner mitochondrial membrane
in eukaryotes and the plasma membrane in prokaryotes. The ETC uses high-energy
electrons from NADH and FADH2 to drive the synthesis of ATP through oxidative
phosphorylation.
To convert the energy stored in NADH and
FADH2 into a proton gradient across the inner
mitochondrial membrane, which drives ATP
synthesis.
Overview of the Electron Transport Chain (ETC)
•For each molecule of NADH: ~2.5 ATP molecules
are generated.
•For each molecule of FADH2: ~1.5 ATP molecules
are generated.
•Total ATP yield from oxidative phosphorylation is
~26-28 ATP per glucose molecule.
Overview of the Electron Transport Chain (ETC)
Pathologies Associated with ETC
•Mitochondrial Diseases:
•Mutations in ETC components can lead to disorders like Leigh syndrome or MELAS, characterized by
impaired energy production.
•Ischemia-Reperfusion Injury:
•During oxygen deprivation (ischemia), ETC function is disrupted. Reintroduction of oxygen can lead to
excessive ROS production, damaging tissues.
•Drug and Toxin Effects:
•Some toxins (e.g., cyanide, carbon monoxide) inhibit Complex IV, blocking the ETC and causing cell
death due to lack of ATP.
•Role in Cancer and Metabolism:
•Alterations in mitochondrial function and ETC activity are often observed in cancer cells, where
metabolism is reprogrammed to meet high energy and biosynthetic demands.
•What is metabolism?
a) The breakdown of nutrients only
b) The chemical reactions within cells to sustain life
c) The storage of energy in cells
d) The production of waste products
•Which of the following best describes catabolism?
a) Building complex molecules from simpler ones
b) Energy storage processes
c) Breaking down molecules to release energy
d) Transport of nutrients across the cell membrane
•ATP is referred to as the "energy currency" of the cell because:
a) It stores large amounts of energy permanently
b) It can easily release and transfer energy to other molecules
c) It is stable and never breaks down
d) It builds proteins directly
•Which of these processes is an example of anabolism?
a) Glycolysis
b) Protein synthesis
c) Digestion of starch
d) Oxidation of fatty acids
1.Redox reactions involve:
a) Transfer of protons between molecules
b) Breaking down glucose to release CO₂
c) Transfer of electrons between molecules
d) Conversion of ATP into ADP
State whether the following statements are true or false. If false, correct the
statement.
1.Catabolic reactions synthesize large molecules and consume energy.
2.Anabolic reactions require energy input to build complex molecules.
3.In redox reactions, reduction refers to the gain of electrons.
4.ATP stores energy in its phosphate bonds, which are broken during
hydrolysis.
5.Enzymes slow down metabolic reactions to ensure control and precision.
•Metabolism is divided into two main categories:
____________, which breaks down molecules, and
____________, which builds molecules.
•ATP releases energy when it is converted into ____________
through the process of ____________.
•A molecule is oxidized when it ____________ electrons,
while reduction means ____________ of electrons.
•Enzymes act as ____________ to speed up metabolic
reactions by lowering the ____________ energy.
•The pathways in metabolism are regulated through
____________, which ensure that cells do not produce
excess products.
•Which of the following metabolic pathways is a catabolic process?
a) Photosynthesis
b) Glycolysis
c) Protein synthesis
d) DNA replication
•The main purpose of catabolic pathways is to:
a) Store energy
b) Build complex molecules
c) Break down nutrients to release energy
d) Maintain pH balance
•Which molecule acts as the immediate energy donor in most cellular
processes?
a) NADH
b) ATP
c) Glucose
d) Acetyl-CoA
•The conversion of ATP to ADP and inorganic phosphate releases energy
because:
a) A high-energy bond is broken
b) A molecule gains a phosphate
c) It forms a stable covalent bond
d) It generates heat
True or False
1.Metabolism only includes catabolic pathways.
2.ATP is a byproduct of metabolic processes.
3.Redox reactions involve either the gain or loss of electrons.
4.Anabolic processes consume energy to build larger
molecules.
5.Glycolysis is an example of a catabolic pathway.
•Metabolism can be divided into two categories: ____________
(building molecules) and ____________ (breaking down
molecules).
•ATP is formed by ____________ and releases energy when it
is hydrolyzed into ADP and ____________.
•The ____________ pathway releases energy by breaking
down organic compounds, while ____________ uses energy to
synthesize necessary cellular components.
•Redox reactions involve the ____________ of electrons from
one molecule to another.
•The primary purpose of glycolysis is to convert glucose into
____________ and generate ____________.
•Metabolism can be divided into two categories: ____________
(building molecules) and ____________ (breaking down
molecules).
•ATP is formed by ____________ and releases energy when it
is hydrolyzed into ADP and ____________.
•The ____________ pathway releases energy by breaking
down organic compounds, while ____________ uses energy to
synthesize necessary cellular components.
•Redox reactions involve the ____________ of electrons from
one molecule to another.
•The primary purpose of glycolysis is to convert glucose into
____________ and generate ____________.
