Notes on MDC Biochemistry

MDC Biochemistry 

Unit - 1

Metal Ions in Biology 

Introduction:

Metal ions are indispensable to life, playing a central role in numerous physiological and biochemical processes. Among them, elements such as sodium (Na⁺), potassium (K⁺), magnesium (Mg²⁺), calcium (Ca²⁺), copper (Cu²⁺), iron (Fe²⁺/Fe³⁺), zinc (Zn²⁺), cobalt (Co²⁺), and molybdenum (Mo) are particularly significant due to their diverse and specific biological functions.

These metal ions are often present as trace elements or electrolytes in body fluids and tissues. They act as enzyme cofactors, electrochemical regulators, and structural stabilizers, and are involved in key biological processes such as nerve transmission, muscle contraction, oxygen transport, energy production, antioxidant defense, DNA synthesis, and metabolic regulation.

Here's a brief overview of each:

Sodium (Na⁺): Maintains fluid balance, nerve impulse conduction, and muscle function.

Potassium (K⁺): Essential for nerve transmission, muscle contraction, and maintaining cellular osmotic balance.

Magnesium (Mg²⁺): Cofactor for over 300 enzymes; crucial in ATP metabolism, DNA/RNA synthesis, and muscle relaxation.

Calcium (Ca²⁺): Key for bone and teeth formation, blood clotting, nerve signaling, and muscle contraction.

Copper (Cu²⁺): Involved in iron metabolism, antioxidant defense (via superoxide dismutase), and formation of connective tissue.

Iron (Fe²⁺/Fe³⁺): Central to oxygen transport in hemoglobin and electron transfer in cellular respiration.

Zinc (Zn²⁺): Participates in immune response, wound healing, and functions as a structural and catalytic cofactor in hundreds of enzymes.

Cobalt (Co²⁺): Found in vitamin B₁₂, essential for red blood cell production and DNA synthesis.

Molybdenum (Mo): Acts as a cofactor for enzymes involved in detoxification and purine metabolism (e.g., xanthine oxidase).

The intricate interplay of these metal ions ensures the proper functioning of the human body. Imbalances—either deficiencies or toxicities—can disrupt cellular function and lead to a variety of diseases, highlighting their critical importance in health and medicine.

Passive and Active Transport in Biology

In biology, transport refers to the movement of substances (such as ions, molecules, or nutrients) across cell membranes. This movement is essential for maintaining cellular homeostasis (Overall state balance of a body) and allowing communication between the cell and its environment. There are two main types of transport mechanisms:

1. Passive Transport

Passive transport is the movement of substances across a cell membrane without the use of cellular energy (ATP). Instead, it relies on the concentration gradient — substances move from an area of high concentration to an area of low concentration (down the gradient).

Types of Passive Transport:

Simple Diffusion: Movement of small, non-polar molecules (like O₂, CO₂) directly through the phospholipid bilayer.

Facilitated Diffusion: Movement of larger or polar molecules (like glucose, ions) through channel or carrier proteins.

Osmosis: The diffusion of water molecules through a selectively permeable membrane.

Key Features:

No energy required

Moves substances down their concentration gradient

Important for gas exchange, nutrient absorption, and water balance

2. Active Transport

Active transport is the movement of substances against their concentration gradient (from low to high concentration) and requires energy, usually in the form of ATP.

Types of Active Transport:

Primary Active Transport: Uses ATP directly (e.g., sodium-potassium pump (Na⁺/K⁺ pump)).

Secondary Active Transport (Co-transport): Uses energy from the movement of one substance down its gradient to move another against its gradient (e.g., glucose-sodium co-transport).

Key Features:

Requires energy input

Moves substances against their concentration gradient

Crucial for maintaining ion gradients, nutrient uptake, and waste removal

Sodium-Potassium Pump (Na⁺/K⁺ Pump)

The sodium-potassium pump is a vital active transport mechanism found in the plasma membrane of most animal cells. It maintains the electrochemical gradient essential for various cellular processes like nerve impulse transmission, muscle contraction, and nutrient absorption.

Function:

The pump actively transports sodium (Na⁺) out of the cell and potassium (K⁺) into the cell, both against their concentration gradients, using energy from ATP.

How It Works (Step-by-Step Mechanism):

1.    Binding of Na⁺ Ions: Three sodium ions inside the cell bind to specific sites on the pump protein.

2.    ATP Hydrolysis: +

The pump hydrolyzes one molecule of ATP to provide the energy needed for transport.

3.    Phosphorylation: A phosphate group from ATP attaches to the pump (phosphorylation), causing a change in the protein's shape.

4.    Na⁺ Release: The shape change allows the pump to release the three Na⁺ ions outside the cell.

5.    Binding of K⁺ Ions: Two potassium ions from outside the cell bind to the pump.

6.    Dephosphorylation: The phosphate group is released, triggering the pump to return to its original shape.

7.    K⁺ Release: The pump releases the two K⁺ ions into the cell, completing the cycle.

Overall Exchange Ratio:

• 3 Na⁺ ions out
• 2 K⁺ ions in
• 1 ATP used per cycle

Biological Importance:

• Maintains resting membrane potential in nerve and muscle cells
• Prepares neurons for action potentials
• Regulates cell volume
• Drives secondary active transport (e.g., glucose and amino acid uptake)

Storage and Transport of Iron, Copper, and Zinc in the Human Body

Iron, copper, and zinc are essential trace metals that support key physiological functions. To avoid toxicity and ensure proper use, the body tightly regulates their transport and storage through specific proteins and mechanisms.

1. Iron (Fe)

Transport:

·Transferrin: The primary iron transport protein in blood. It binds Fe³⁺ (ferric iron) and delivers it to cells via transferrin receptors.

·Inside cells, iron is reduced to Fe²⁺ (ferrous) and used in processes like hemoglobin synthesis, electron transport, and enzyme activity.

Storage:

·Ferritin: A protein that safely stores excess iron inside cells, especially in the liver, spleen, and bone marrow. It can hold up to 4500 iron atoms.

·Hemosiderin: An insoluble form of stored iron, seen in cases of iron overload.

2. Copper (Cu)

Transport:

·Ceruloplasmin: The major copper-carrying protein in blood, which also oxidizes Fe²⁺ to Fe³⁺ for binding to transferrin.

·Albumin and amino acids also bind small amounts of copper for transport.

·Inside cells, copper is carried by chaperone proteins (like ATOX1, CCS) to prevent free copper toxicity and deliver it to enzymes (e.g., cytochrome c oxidase, superoxide dismutase).

Storage:

·Copper is stored in small amounts, mainly in the liver, brain, and muscle tissues, bound to proteins like metallothionein.

·The body tightly controls copper levels through regulated absorption and bile excretion.

3. Zinc (Zn)

Transport:

·Zinc circulates bound to albumin (major transporter), and also with other proteins like α2-macroglobulin.

· Two main families of transport proteins regulate cellular zinc:

oZIP (Zrt- and Irt-like proteins): Increase cytoplasmic zinc by transporting it into cells.

oZnT (Zinc Transporters): Remove zinc from cells or into organelles.

Storage:

·Stored bound to metallothionein, mainly in the liver, pancreas, kidney, and muscles.

Zinc is not stored in a large pool like iron; instead, its concentration is regulated by transport and binding proteins.

Chemistry of Porphyrins

Porphyrins are a class of organic compounds composed of four pyrrole rings linked together by methine (=CH−) bridges, forming a macrocyclic structure called a porphin ring.

Structure:

• The basic structure is a tetrapyrrolic macrocycle.
• The large, planar, conjugated system allows delocalization of electrons, giving porphyrins their intense color (usually red or purple).

Coordination Chemistry:

• Porphyrins can bind metal ions at the center of the ring, forming metalloporphyrins.
• Common examples:
• Fe²⁺ in heme (oxygen transport in hemoglobin)
• Mg²⁺ in chlorophyll (photosynthesis in plants)
• Co²⁺ in vitamin B₁₂ (coenzyme functions)

Biological Importance:

• Heme proteins (e.g., hemoglobin, myoglobin, cytochromes) use porphyrins to carry or transfer electrons or oxygen.
• The metal ion at the center determines the function of the porphyrin complex.

Chemical Properties:

• Exhibit strong absorption in the visible region (Soret band).
• Undergo oxidation-reduction (redox) reactions.

Chemistry of Iron Porphyrins

Iron porphyrins are a class of coordination compounds where an iron ion (Fe²⁺ or Fe³⁺) is centrally bound within a porphyrin ring — a large, planar, macrocyclic ligand composed of four pyrrole subunits linked by methine bridges. These structures are fundamental to many biological molecules, including heme, which is the prosthetic group in hemoglobin, myoglobin, and various cytochromes.

By Smokefoot - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=30296258

Structure of Iron Porphyrins:

See the above  structure of a picket-fence porphyrin complex of Fe, with axial coordination sites occupied by methylimidazole (green) and dioxygen (R = amide groups)

Porphyrin Ring: A tetrapyrrole ring system (C₂₀H₁₄N₄) forming a stable, aromatic, conjugated macrocycle.

Iron Center: Iron ion coordinates to the four nitrogen atoms of the pyrrole rings.

Axial Ligands: One or two additional ligands can bind to the iron above and below the plane of the porphyrin (e.g., O₂, CO, H₂O, His residue).

Types and Oxidation States

Iron in porphyrins typically exists in two oxidation states:

Fe(II) – Ferrous: Active in reversible oxygen binding (as in hemoglobin).

Fe(III) – Ferric: Found in oxidized forms; can participate in redox reactions (as in cytochromes or catalase).

Key Reactions of biological molecules and their Functions:

Hemoglobin/Myoglobin : Binds and transports O₂ in blood/muscle

Cytochromes (e.g., Cyt c): Electron transfer in mitochondrial respiration

Cytochrome P450: Catalyzes oxidation of organic substrates (drug metabolism)

Catalase/Peroxidase: Detoxifies hydrogen peroxide via redox cycling

Coordination Chemistry Features:

Ligand Field: Square planar base with potential octahedral coordination.

Backbonding: In Fe(II), π-backbonding with ligands like CO and NO occurs.

Spin States: Can exhibit high-spin or low-spin configurations depending on ligands and oxidation state.

Significance in Bioinorganic Chemistry

Iron porphyrins are central to:

• Oxygen transport and storage.
• Electron transfer and redox chemistry.
• Catalysis in biological and industrial systems (e.g., biomimetic catalysts).
• Design of drugs and artificial enzymes.

Unit -2:

Biomolecular Catalysis:

Metal-Activated Enzymes and Metalloenzymes:

These are two types of metal-containing enzymes, important in many biological processes. Here's a clear comparison:

 Metal-Activated Enzymes

Definition:
Enzymes that require a metal ion for activity or stability, but the metal is not tightly bound to the enzyme.

Key Features:

Metal ions are loosely bound and can be easily removed or replaced.

Metal is not a permanent part of the enzyme structure.

Often activated by alkali or alkaline earth metals (e.g., K⁺, Mg²⁺, Ca²⁺).

The metal ion helps in substrate binding or stabilization of enzyme structure.

Examples:

• DNA polymerase (activated by Mg²⁺)
• Amylase (activated by Ca²⁺)
• ATPase (activated by Mg²⁺)

Metalloenzymes

Definition:
Enzymes that contain tightly bound metal ions which are essential for their catalytic activity.

Key Features:

Metal ions are firmly attached (often through coordination with amino acid side chains).

Metals often participate directly in the catalytic mechanism.

Cannot function without the specific metal ion.

Typically contain transition metals like Fe, Zn, Cu, Mn, Co, Ni.

Examples:

• Carbonic anhydrase (contains Zn²⁺)
• Cytochrome c oxidase (contains Fe and Cu)
• Nitrogenase (contains Fe and Mo)
• Superoxide dismutase (contains Mn²⁺ or Cu/Zn)

Carboxypeptidase: Biological Significance & Mechanistic Aspects

I. Biological Significance of Carboxypeptidase

Definition:
Carboxypeptidases are exo-peptidases (enzymes that cleave amino acids from the ends of polypeptides) which specifically remove amino acids from the C-terminal end of proteins and peptides.

Types of Carboxypeptidases:

1.    Carboxypeptidase A – prefers aromatic or aliphatic residues.

2.    Carboxypeptidase B – removes basic residues like arginine and lysine.

3.    Carboxypeptidase E, H, etc. – found in neuroendocrine tissues.

Biological Roles:

·         Protein digestion:

In the digestive tract (e.g., pancreas), helps complete protein breakdown into free amino acids.

·         Hormone processing:

In neuroendocrine cells, it activates or matures peptide hormones by removing C-terminal residues.

·         Wound healing and tissue remodeling:

Regulates extracellular matrix proteins.

·         Cell signaling and immunity:

Involved in activation/inactivation of signaling peptides.

II. Mechanistic Aspects of Carboxypeptidase A

Structure and Cofactor:

·         Metalloenzyme containing Zn²⁺ at the active site.

·         Zn²⁺ is essential for polarizing the peptide bond and activating water for nucleophilic attack.

Catalytic Mechanism:

1.    Substrate Binding:

The C-terminal end of the peptide binds in the active site, positioned near the Zn²⁺.

2.    Activation of Water:

Zn²⁺ coordinates with a water molecule and lowers its pKa, turning it into a hydroxide ion (OH⁻).

3.    Nucleophilic Attack:

OH⁻ attacks the carbonyl carbon of the scissile (cleavable) peptide bond.

4.    Tetrahedral Intermediate:

A transition state forms, stabilized by the enzyme.

5.    Bond Cleavage:

The peptide bond is broken, and the C-terminal amino acid is released.

6.    Product Release:

The shortened peptide is released from the enzyme.

Key Residues in Active Site:

·         His⁶⁹, Glu⁷², His¹⁹⁶ – coordinate Zn²⁺

·         Glu²⁷⁰ – acts as a general base to assist water activation

Overall Reaction:

Interesting Facts:

·         Inhibited by chelating agents like EDTA (which remove Zn²⁺).

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Carbonic Anhydrase

Definition:

Carbonic anhydrase (CA) is a zinc metalloenzyme that catalyzes the reversible hydration of carbon dioxide:

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I. Biological Significance of Carbonic Anhydrase

1. Gas Exchange and Respiration:

·         Facilitates CO₂ transport from tissues to lungs by converting it into bicarbonate (HCO₃⁻).

·         In lungs, converts bicarbonate back to CO₂ for exhalation.

2. pH Regulation:

·         Maintains acid-base balance in blood and tissues by controlling proton (H⁺) and bicarbonate levels.

3. Electrolyte Secretion:

·         Helps in secretion of fluids in eye (aqueous humor), stomach (gastric juice), pancreas, and cerebrospinal fluid.

4. Kidney Function:

·         Participates in reabsorption of bicarbonate in renal tubules to regulate systemic pH.

5. Photosynthesis (in plants):

·         Helps in concentrating CO₂ for Rubisco enzyme in C₄ and CAM plants, enhancing photosynthetic efficiency.

II. Mechanistic Aspects of Carbonic Anhydrase

Structure and Active Site:

·         Contains a Zn²⁺ ion coordinated tetrahedrally by three histidine residues and a water molecule.

Catalytic Mechanism:

1.    Water Activation:

o    Zn²⁺ polarizes the coordinated water molecule, lowering its pKa.

o    A hydroxide ion (OH⁻) is formed at the active site.

2.    Nucleophilic Attack:

o    The OH⁻ attacks the carbon atom of CO₂.

o    This forms bicarbonate (HCO₃⁻).

3.    Bicarbonate Release:

o    Bicarbonate ion is released from the active site.

4.    Regeneration:

o    A new water molecule enters and displaces the bicarbonate.

o    A proton is shuttled out (via a histidine residue), regenerating the OH⁻.

Key Catalytic Features of various components of the enzyme:

Zn²⁺ ion: Activates water for nucleophilic attack

His residues: Coordinate Zn²⁺ and shuttle protons

OH⁻ ion: Attacks CO₂ to form bicarbonate

Water: Restores the catalytic site after reaction

Fun Fact:

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Carbonic anhydrase is one of the fastest enzymes known, with a turnover rate of over 1 million molecules of CO₂ per second.

Unit - 3

Basic Bioorganic Chemistry

Proximity Effect in Organic Chemistry:

The proximity effect in organic chemistry refers to the influence that spatial closeness (or proximity) of reactive groups or atoms within a molecule has on the rate or outcome of a chemical reaction. It often enhances reactivity by reducing the entropy of activation and effectively bringing reactive centers closer together.

Key Concepts:

1.    Intramolecular Reactions:

o    When two reactive groups are within the same molecule and positioned close to each other, they can react more easily than if they were in separate molecules.

o    This is due to less energy required to bring them together, as they are already "pre-organized."

2.    Reduced Activation Energy:

o    The proximity lowers the entropy of activation (ΔS‡), making the transition state easier to achieve and thus increasing the reaction rate.

3.    Common in Enzyme Catalysis:

o    Enzymes use the proximity effect by holding substrates in the correct orientation and close proximity, significantly speeding up biochemical reactions.

Examples:

1.    Ester Hydrolysis (Intramolecular vs. Intermolecular):

o    Intramolecular hydrolysis (like in lactone formation) happens faster than intermolecular ester hydrolysis due to the proximity of nucleophile and electrophile.

2.    Neighboring Group Participation (NGP):

o    A nearby lone pair or π-bond can assist in reaction mechanisms (e.g., SN1 or SN2), stabilizing intermediates or transition states.

Example: In SN1 reactions, an adjacent OH or OR group can stabilize the carbocation through anchimeric assistance, speeding up the reaction.

3.    Intramolecular Aldol Reaction:

o    Aldol reactions between two carbonyl groups in the same molecule proceed faster and with higher selectivity than intermolecular ones due to the proximity of the reacting groups.

Significance:

• Used in synthetic organic chemistry to design more efficient, selective, and faster reactions.
• Helps explain enzyme efficiency and rate enhancements in biological systems.

        Basis for molecular preorganization in drug design and catalysis.

Molecular Adaptations:

Adaptation is the process of changing to suit different conditions.

Molecular adaptations are biochemical or genetic changes at the molecular level (DNA, RNA, proteins, or metabolites) that allow organisms to survive, reproduce, and thrive in specific environments. These adaptations result from natural selection acting on mutations that enhance fitness in a given ecological context.

Types of Molecular Adaptations:

1.    Genetic Adaptations

o    Point mutations, gene duplications, insertions, deletions, or chromosomal rearrangements that provide an advantage.

o    Example: Sickle cell mutation (HbS) provides resistance to malaria in heterozygous individuals.

2.    Protein-Level Adaptations

o    Structural or functional changes in proteins (e.g., enzymes) that improve stability, efficiency, or activity in certain environments.

o    Example: Antifreeze proteins in Arctic fish prevent ice crystal formation in blood.

3.    Enzymatic Adaptations

o    Altered enzymes to function at different temperatures, pH levels, or salinity.

o    Example: Thermophilic enzymes (e.g., Taq polymerase from Thermus aquaticus) remain active at high temperatures.

4.    Membrane Lipid Composition

o    Changes in fatty acid composition to maintain fluidity under cold or hot conditions.

o    Example: Arctic organisms increase unsaturated lipids for membrane fluidity in freezing temperatures.

5.    Gene Regulation Adaptations

o    Differences in when, where, and how genes are expressed.

o    Example: Desert plants regulate genes for stomatal closure and CAM metabolism to conserve water.

6.    Metabolic Pathway Shifts

o    Redirection of metabolic flows for survival in nutrient-limited or extreme environments.

o    Example: Anaerobic bacteria adapt their metabolism to survive without oxygen.

Examples from Nature, how different organisms adapt to different conditions by suitable molecular mechanism:

Bar headed goose (A bird) reaches extreme altitude while migrating across Himalayas: At this altitude, the hemoglobin mutation increases the oxygen affinity to survive.

Deep Sea Fish tolerates high pressure and darkness: It is possible due to Proteins adapted to high pressure and photophores for bioluminescence or light.

Tibetan humans live in high altitude: Possible due to Mutation in EPAS1 gene regulates red blood cell production

Cactus plant remain alive by resisting drought: Possible due to CAM gene expression for water-efficient photosynthesis

Bacteria in hydrothermal vents resist high temperature: possible due to Thermostable enzymes and chaperone proteins

Importance of Molecular Adaptations:

• Allow life to exist in extreme environments (e.g., hot springs, Antarctica, deep oceans).
• Provide insight into evolutionary processes and natural selection.
• Useful in biotechnology, medicine, and agriculture (e.g., GM crops, industrial enzymes).

    Help us understand disease resistance and adaptation (e.g., antibiotic resistance in bacteria).

Enzyme Mechanism of Chymotrypsin:

Chymotrypsin is a serine protease enzyme that catalyzes the hydrolysis of peptide bonds, specifically those adjacent to aromatic amino acids (like phenylalanine, tyrosine, and tryptophan). It is secreted by the pancreas in its inactive form chymotrypsinogen, and activated in the small intestine.

Type of Reaction:

• Proteolytic cleavage (breaking peptide bonds by hydrolysis)
• Occurs via a covalent catalysis and acid-base catalysis mechanism

Catalytic Triad Involved:

The active site of chymotrypsin contains three essential amino acid residues forming a catalytic triad:

1.    Serine 195 – acts as a nucleophile

2.    Histidine 57 – acts as a base and acid

3.    Aspartate 102 – stabilizes histidine and orients it properly

Stepwise Mechanism of Chymotrypsin Action:

Phase 1: Acylation Phase

1.    Substrate Binding:

o    The substrate peptide binds to the enzyme’s hydrophobic pocket, aligning the scissile bond with Ser195.

2.    Nucleophilic Attack:

o    His57 deprotonates Ser195, activating it.

o    The now nucleophilic Ser195 attacks the carbonyl carbon of the peptide bond.

3.    Tetrahedral Intermediate Formation:

o    A high-energy tetrahedral intermediate is formed and stabilized by the oxyanion hole.

4.    Breakage of Peptide Bond:

o    His57 donates a proton to the leaving amine group.

o    The bond breaks, releasing the C-terminal end of the peptide.

o    The remaining part is covalently linked to Ser195 as an acyl-enzyme intermediate.

Phase 2: Deacylation Phase

5.    Water Activation:

o    A water molecule enters the active site.

o    His57 deprotonates water, generating a hydroxide ion.

6.    Nucleophilic Attack by Water:

o    The hydroxide ion attacks the acyl-enzyme intermediate, forming another tetrahedral intermediate.

7.    Release of the Product:

o    The tetrahedral intermediate collapses.

o    The N-terminal end of the peptide is released.

                   The free enzyme is regenerated.

Unit - 4

Metabolism of Biomolecules:

Sources and Nutritive Roles of Carbohydrates

I. Sources of Carbohydrates

Carbohydrates are mainly found in plant-based foods, though some are present in dairy. They are classified based on their chemical structure into simple (sugars) and complex (starches and fibers).

A. Natural Sources

1.    Cereals and Grains

o    Examples: Rice, wheat, corn, oats, barley

o    Main Carb Type: Starch (complex carbohydrate)

2.    Fruits

o    Examples: Banana, apple, mango, grapes

o    Main Carb Type: Glucose, fructose, sucrose (simple sugars)

3.    Vegetables

o    Examples: Potatoes, carrots, beets, peas

o    Main Carb Type: Starch and dietary fiber

4.    Legumes and Pulses

o    Examples: Lentils, chickpeas, beans

o    Main Carb Type: Starch and dietary fiber

5.    Dairy Products

o    Examples: Milk, yogurt

o    Main Carb Type: Lactose (milk sugar)

6.    Sugary Foods

o    Examples: Honey, sugarcane, jaggery

o    Main Carb Type: Sucrose, glucose, fructose

II. Nutritive Roles of Carbohydrates

Carbohydrates are essential macronutrients that perform several vital functions in the body:

1. Primary Energy Source

·  Carbohydrates are the body's main fuel, especially for the brain and muscles.

·         Each gram provides 4 kcal of energy.

·         Glucose is the most readily used form of energy.

2. Protein-Sparing Action

·   When carbohydrate intake is sufficient, proteins are spared from being used for energy and can be used for growth and repair.

3. Fat Metabolism

·         Carbohydrates are essential for the proper oxidation of fats.

·   Lack of carbs leads to incomplete fat breakdown, causing ketone body formation (ketosis).

4. Fiber for Digestive Health

·  Complex carbs like dietary fiber (e.g., cellulose) help regulate bowel movements, prevent constipation, and lower cholesterol.

5. Regulation of Blood Sugar

·     Complex carbohydrates help maintain stable blood glucose levels.

·    Fiber slows down glucose absorption.

6. Synthesis of Body Compounds

·   Carbohydrates are involved in the formation of glycoproteins, glycolipids, and nucleotides (e.g., ribose in RNA, deoxyribose in DNA).

Glycolysis

Definition:
Glycolysis is the metabolic pathway that breaks down glucose (C₆H₁₂O₆) into pyruvate, releasing energy in the form of ATP and NADH. It occurs in the cytoplasm of all living cells and does not require oxygen (anaerobic process).

Key Features:

·         Location: Cytoplasm

·         Oxygen requirement: Anaerobic

·         Starting molecule: Glucose (6-carbon)

·         End products:

o    2 Pyruvate (3-carbon each)

o    2 ATP (net gain)

o    2 NADH

Phases of Glycolysis:

1. Preparatory Phase (Energy Investment Phase):

·         Steps 1–5

·         2 ATP molecules are used to phosphorylate glucose and convert it into two molecules of glyceraldehyde-3-phosphate (G3P).

2. Pay-off Phase (Energy Generation Phase):

·         Steps 6–10

·         Each G3P is converted into pyruvate, generating 4 ATP and 2 NADH in total.

Steps of Glycolysis (Simplified):

Net Gain from 1 Glucose Molecule:

Molecule	Net Gain
ATP	2
NADH	2
Pyruvate	2

(Total ATP produced = 4; ATP used = 2 → Net = 2 ATP)

Fate of Pyruvate:

Depends on oxygen availability:

·         Aerobic: Converted to acetyl-CoA → enters Krebs cycle

·         Anaerobic (in muscles): Converted to lactic acid

·         Anaerobic (in yeast): Converted to ethanol + CO₂

Importance of Glycolysis:

·         Provides quick energy.

·         Operates in all cells (including those without mitochondria).

            First step in cellular respiration.