Heterocyclic Compounds and Enzymes cofactors test no.2

• Heterocyclic compounds are organic compounds with ring structures where one or more carbon atoms are replaced by heteroatoms like oxygen (O), nitrogen (N), or sulfur (S).

Classification of Heterocyclic Compounds

• By number of atoms in the ring:
  • Three-membered: Thiirane
  • Four-membered: Oxetane
  • Five-membered: Pyrrole
  • Six-membered: Pyridine
• By type of heteroatoms:
  • Same heteroatoms: Imidazole, Pyrimidine
  • Different heteroatoms: Thiazole
• By number of rings:
  • Monocyclic: Pyrimidine
  • Polycyclic: Purine

Examples and Bioactivity of Heterocyclic Compounds

• Pyrrole derivatives are found in porphyrins, such as heme, essential for oxygen transport
• Indole derivatives include neurotransmitters like serotonin
• Pyrimidine bases: Cytosine, Thymine, Uracil are components of DNA/RNA
• Purine bases: Adenine, Guanine are components of DNA/RNA
• Heterocyclic compounds function as vitamins, drugs, hormones, and pigments

Purine and Pyrimidine Heterocyclic Bases

• Purines: Fused ring system (pyrimidine + imidazole); examples include Adenine (A) and Guanine (G)
• Pyrimidines: Six-membered ring; examples include Cytosine (C), Thymine (T), and Uracil (U)

Tautomerization

• Lactam (keto form) and Lactim (enol form) are tautomers
• Affects base pairing and can cause mutations
• Purine and pyrimidine bases exist in these forms depending on pH

Nucleosides

• Composed of a nitrogenous base linked to a sugar (ribose or deoxyribose) via a β-N-glycosidic bond
• Naming: Purines (add "-osine" like Adenosine, Guanosine); Pyrimidines (add "-idine" like Cytidine, Thymidine, Uridine)

Nucleotides

• Nucleoside + phosphate group(s) attached at the 5' carbon of the sugar.
  • Monophosphate (AMP, GMP)
  • Diphosphate (ADP, GDP)
  • Triphosphate (ATP, GTP)
• Functions: DNA and RNA building blocks, energy carriers (ATP), second messengers (cAMP), cell signaling (G-proteins)

Nucleic Acids: Primary and Secondary Structures

• Primary Structure: Linear sequence of nucleotides joined by phosphodiester bonds, read from the 5' to the 3' end
• Secondary Structure:
  • DNA: Double helix with two antiparallel strands; Complementary base pairing: A-T (2 H-bonds), G-C (3 H-bonds)
  • RNA: Single-stranded, forms secondary structures (e.g., hairpins)

Examples of Nucleic Acids

• DNA (Deoxyribonucleic Acid): Bases - A, G, C, T; Sugar - Deoxyribose; Double-stranded, stores genetic information
• RNA (Ribonucleic Acid): Bases - A, G, C, U; Sugar - Ribose; Single-stranded, involved in protein synthesis and regulation
  • Types: mRNA (messenger RNA), rRNA (ribosomal RNA), tRNA (transfer RNA)

Enzymes

• Biological catalysts that speed up chemical reactions in living organisms without being consumed
• Found inside cells and sometimes secreted (e.g., digestive enzymes)
• Each enzyme catalyzes a specific reaction

Enzyme Classes (EC Classification)

• Oxidoreductases (EC 1): catalyze oxidation/reduction reactions (e.g., Alcohol dehydrogenase)
• Transferases (EC 2): transfer functional groups (e.g., Aminotransferases)
• Hydrolases (EC 3): catalyze hydrolysis of bonds (e.g., Proteases, Carboxypeptidase)
• Lyases (EC 4): cleave bonds by means other than hydrolysis/oxidation (e.g., Pyruvate decarboxylase)
• Isomerases (EC 5): catalyze isomerization (e.g., Maleate isomerase)
• Ligases (EC 6): join molecules using ATP (e.g., Pyruvate carboxylase)
• Translocases (EC 7): catalyze movement of ions/molecules across membranes (new class added in 2018)

Enzyme Nomenclature

• Often ends in -ase, indicating substrate or function (e.g., lipase, urease)
• Assigned an EC number for systematic classification (e.g., EC 1.1.1.1 for Alcohol dehydrogenase)

Enzyme Properties

• High catalytic efficiency to accelerate reactions up to 10^8–10^20 times, with specificity for substrates
• Regulated by pH, temperature, and inhibitors, and are sensitive to denaturation

Enzyme Mechanisms

• Active site: region where substrate binds, forming an enzyme-substrate complex to facilitate reaction
• Lock and Key Model: active site perfectly fits substrate
• Induced Fit Model: active site adjusts shape to substrate

Enzyme Inhibition

• Reversible:
  • Competitive: inhibitor mimics substrate, binds active site (e.g., Statins)
  • Non-competitive: binds elsewhere, altering enzyme shape
• Irreversible: inhibitor covalently binds enzyme, permanently inactivating it (e.g., aspirin on COX enzyme)
• Regulation: Activators (e.g., metal ions) and inhibitors affect activity

Cofactors

• Non-protein helpers needed for enzyme activity, such as inorganic ions (e.g., Mg2+, Ca2+, Fe2+, Zn2+)
• Metalloenzymes: contain tightly bound metal ions at active sites (e.g., Carbonic anhydrase with Zn2+)

Coenzymes

• Organic molecules assisting enzymes, often derived from vitamins

Coenzyme Examples and Functions

• NAD, NADP+ (Vitamin B3 derivatives) – redox reactions
• FAD, FMN (Vitamin B2 derivatives) – redox reactions
• TPP (Thiamine pyrophosphate) – decarboxylation (Vitamin B1)
• PLP (Pyridoxal phosphate) – transamination (Vitamin B6)
• Coenzyme A (CoA-SH) – acyl group transfer (Vitamin B5)
• Biotin – carboxylation reactions (Vitamin B7)
• Cobalamin (B12) – methylation and red blood cell formation
• THFA (Folate derivative) – nucleotide synthesis (Vitamin B9)
• Participate in energy production (ATP-related reactions), redox reactions, group transfers (e.g., methyl, acyl), and decarboxylation and transamination in metabolism

Coenzymes and Vitamins

• Derived from water-soluble vitamins, especially B-group and Vitamin C
  • Vitamin C: Important antioxidant for collagen synthesis and hormone production
  • Vitamin B complex: Vital for energy metabolism, DNA synthesis, and neurotransmitter function

Vitamin and Coenzyme Structures and Functions Table

• B1 (Thiamin): Thiamine pyrophosphate (TPP); Decarboxylation, Transketolase reactions
• B2 (Riboflavin): FAD, FMN; Redox reactions in metabolism
• B3 (Niacin): NAD*, NADP+; Redox reactions, energy metabolism
• B5 (Pantothenic acid): Coenzyme A (CoA-SH); Acyl group transfers, fatty acid metabolism
• B6 (Pyridoxine, Pyridoxal): Pyridoxal phosphate (PLP); Amino acid metabolism, transamination, decarboxylation
• B7 (Biotin): Biotin (prosthetic group); Carboxylation reactions
• B9 (Folic Acid): THFA (tetrahydrofolate); One-carbon transfers, nucleotide synthesis
• B12 (Cobalamin): Methylcobalamin, 5'-deoxyadenosylcobalamin; Methyl group transfers, RBC formation
• Vitamin C (Ascorbic acid): Ascorbate; Antioxidant, collagen synthesis, catecholamine synthesis