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COURSE: BIOCHEM 385: Medical Biochemistry LECTURE NOTES: Biomolecules – The Molecules of Life and Their Medical Significance Date: June 16, 2024 Topic: An In-depth Exploration of Biomolecules: Structure, Function, and Clinical Correlations
I. INTRODUCTION TO BIOMOLECULES IN MEDICAL
BIOCHEMISTRY
Biochemistry is the science that explores the chemical processes within and related to living organisms. Medical biochemistry , specifically, deals with the biochemical basis of human health and disease. At the heart of this discipline are biomolecules , the organic molecules that constitute living matter and participate in the myriad of reactions that sustain life. A. Defining Biomolecules: Biomolecules are carbon-based compounds, characterized by their complexity and organized structure. They range from small monomers to large polymers. The principal elements found in biomolecules include carbon (C), hydrogen (H), oxygen (O), nitrogen (N), phosphorus (P), and sulfur (S). These elements combine to form a vast array of molecules with diverse structures and functions. B. Hierarchical Organization: Living systems exhibit a hierarchical organization of biomolecules:
- Monomers (Simple Building Blocks): Small molecules like monosaccharides, amino acids, fatty acids, and nucleotides.
- Macromolecules (Polymers): Large, complex molecules formed by the polymerization of monomers. These include polysaccharides, proteins, lipids (though not strictly polymers in the same way, they form large aggregates and structures), and nucleic acids.
- Supramolecular Complexes: Assemblies of macromolecules, such as ribosomes, enzymes, lipoproteins, and chromatin.
- Organelles: Functional units within cells, like mitochondria, nucleus, and endoplasmic reticulum, composed of supramolecular complexes.
- Cells: The basic unit of life. C. The Aqueous Milieu: Water Water is the most abundant molecule in living systems, typically constituting 70-80% of cell mass. Its unique properties are fundamental to the structure and function of biomolecules: ● Polarity and Hydrogen Bonding: Water's polarity and ability to form hydrogen bonds make it an excellent solvent for polar biomolecules (hydrophilic substances) and influence the folding of macromolecules. ● Hydrophobic Effect: The tendency of nonpolar molecules (hydrophobic substances) to aggregate in aqueous solutions is a primary driving force in the formation of membranes and the folding of proteins. ● High Specific Heat: Helps maintain temperature homeostasis. ● Ionization: Water can ionize to H⁺ and OH⁻, influencing pH and participating in acid-base reactions critical for enzymatic activity. D. Significance in Medicine: Understanding biomolecules is paramount in medicine because: ● Pathophysiology of Disease: Alterations in the structure, function, or metabolism of biomolecules underlie virtually all diseases (e.g., genetic diseases due to DNA mutations, metabolic disorders like diabetes due to defects in carbohydrate/hormone function). ● Diagnostics: Many biomolecules serve as biomarkers for disease diagnosis, prognosis,
and monitoring treatment efficacy (e.g., glucose levels in diabetes, enzyme levels after myocardial infarction). ● Therapeutics: Drugs often target specific biomolecules (e.g., enzyme inhibitors, receptor antagonists). Gene therapy aims to correct defects at the nucleic acid level. ● Nutrition: Provides the raw materials (essential amino acids, fatty acids, vitamins) for synthesizing and maintaining biomolecules.
II. CARBOHYDRATES (GLYCANS)
Carbohydrates, with the general formula (CH_2O)_n, are the most abundant organic molecules in nature. They serve critical roles as energy sources, structural components, and signaling molecules. A. Classification and Structure:
- Monosaccharides (Simple Sugars): ○ Definition: The simplest carbohydrates that cannot be hydrolyzed into smaller units. Classified by the number of carbon atoms (trioses, tetroses, pentoses, hexoses) and the nature of the carbonyl group (aldoses have an aldehyde; ketoses have a ketone). ○ Key Examples: ■ Glucose (Dextrose): An aldohexose (C_6H_{12}O_6), the primary energy source for most cells. Exists in linear and cyclic (pyranose) forms, with \alpha and \beta anomers. (Illustration: Fischer projection and Haworth projection of \alpha-D-glucose and \beta-D-glucose would be shown here.) ■ Fructose (Levulose): A ketohexose, found in fruits and honey. Metabolized primarily in the liver. Forms furanose rings. ■ Galactose: An aldohexose, an epimer of glucose (differs at C4). A component of lactose. ■ Ribose and Deoxyribose: Aldopentoses, components of RNA and DNA, respectively. Deoxyribose lacks an oxygen atom at C2. ○ Isomerism: Monosaccharides exhibit various forms of isomerism, including enantiomers (D- and L-sugars, D-isomers are predominant in humans), diastereomers, epimers, and anomers.
- Disaccharides: ○ Definition: Formed by the linkage of two monosaccharides via a glycosidic bond (an O-glycosidic bond if through an oxygen, or N-glycosidic if through a nitrogen). The bond is formed by a dehydration reaction. ○ Key Examples: ■ Sucrose (Table Sugar): Glucose + Fructose (\alpha1 \rightarrow \beta glycosidic bond). Non-reducing sugar. ■ Lactose (Milk Sugar): Galactose + Glucose (\beta1 \rightarrow 4 glycosidic bond). Reducing sugar. Requires lactase for digestion. ■ Maltose (Malt Sugar): Glucose + Glucose (\alpha1 \rightarrow 4 glycosidic bond). Reducing sugar. Product of starch digestion. (Illustration: Structures of sucrose, lactose, and maltose showing glycosidic bonds would be presented.)
- Oligosaccharides: ○ Composed of 3-10 monosaccharide units. Often found covalently attached to
absolute insulin deficiency. ○ Type 2 Diabetes: Insulin resistance and relative insulin deficiency. ○ Complications: Long-term hyperglycemia leads to glycation of proteins (e.g., hemoglobin A1c, a diagnostic marker), microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (atherosclerosis) complications.
- Lactose Intolerance: Deficiency of the enzyme lactase, leading to inability to digest lactose. Results in abdominal pain, bloating, diarrhea upon lactose ingestion.
- Galactosemia: Genetic disorder due to deficiency of enzymes involved in galactose metabolism (e.g., galactose-1-phosphate uridyltransferase). Accumulation of galactose and its metabolites causes liver damage, cataracts, and intellectual disability.
- Glycogen Storage Diseases (GSDs): A group of inherited disorders caused by defects in enzymes of glycogen synthesis or degradation. Lead to abnormal glycogen accumulation or structure, affecting liver, muscle, or other tissues. ○ Examples: Von Gierke's disease (Type I, glucose-6-phosphatase deficiency), Pompe disease (Type II, lysosomal \alpha-1,4-glucosidase deficiency), McArdle disease (Type V, muscle glycogen phosphorylase deficiency).
- Mucopolysaccharidoses (MPS): Lysosomal storage diseases caused by deficiencies of enzymes that degrade GAGs. Accumulation of GAGs leads to progressive damage to various tissues. ○ Examples: Hurler syndrome (MPS I), Hunter syndrome (MPS II).
- Dietary Fiber: Non-digestible carbohydrates (e.g., cellulose, pectin) play roles in gut health, regulating bowel movements, and can influence cholesterol and glucose absorption.
- Dental Caries: Oral bacteria metabolize dietary sugars to acids, which demineralize tooth enamel.
III. LIPIDS
Lipids are a heterogeneous group of hydrophobic or amphipathic biomolecules that are soluble in organic solvents (e.g., chloroform, ether) and largely insoluble in water. They serve diverse and critical functions. A. Classification and Structure:
- Fatty Acids (FAs): ○ Definition: Carboxylic acids with long hydrocarbon chains (typically 4 to 36 carbons). Can be saturated (no double bonds) or unsaturated (one or more double bonds). ○ Nomenclature: C_x:y (\Delta^{z_1, z_2,...}), where x = number of carbons, y = number of double bonds, z = position of double bonds from carboxyl end. Omega (\omega) numbering denotes position from methyl end. ○ Saturated FAs (SFAs): e.g., Palmitic acid (C16:0), Stearic acid (C18:0). Tend to be solid at room temperature. ○ Unsaturated FAs: ■ Monounsaturated FAs (MUFAs): One double bond, e.g., Oleic acid (C18:1$\Delta^9$). ■ Polyunsaturated FAs (PUFAs): Two or more double bonds, e.g., Linoleic acid (C18:2$\Delta^{9,12}, an $\omega$-6 FA), $\alpha$-Linolenic acid (C18:3\Delta^{9,12,15}$, an \omega-3 FA).
■ Double bonds are usually in the cis configuration, creating kinks in the chain. Trans fatty acids (often from industrial hydrogenation) have straighter chains and are associated with adverse health effects. ○ Essential Fatty Acids: Cannot be synthesized by humans and must be obtained from the diet (e.g., linoleic acid, \alpha-linolenic acid). Precursors for eicosanoids. (Illustration: Structures of palmitic acid, oleic acid, and linoleic acid, highlighting saturation and cis-double bonds.)
- Triacylglycerols (Triglycerides, TAGs): ○ Definition: Esters of glycerol with three fatty acids. The major storage form of energy in adipose tissue. Highly hydrophobic. ○ Structure: Glycerol backbone esterified to three FAs. Simple TAGs have identical FAs; mixed TAGs have different FAs. (Illustration: Structure of a triacylglycerol.)
- Phospholipids (Glycerophospholipids and Sphingophospholipids): ○ Definition: Major components of cell membranes. Amphipathic molecules with a polar head group and two nonpolar fatty acid tails. ○ Glycerophospholipids (Phosphoglycerides): ■ Structure: Glycerol-3-phosphate backbone esterified to two fatty acids at C and C2, and a polar head group (alcohol) attached to the phosphate at C3. ■ Common head groups: Choline (phosphatidylcholine/lecithin), ethanolamine (phosphatidylethanolamine/cephalin), serine (phosphatidylserine), inositol (phosphatidylinositol - important in signaling). ■ Cardiolipin: Two phosphoglycerides linked by a glycerol, found in inner mitochondrial membrane. ○ Sphingophospholipids: ■ Structure: Sphingosine backbone (a long-chain amino alcohol). A fatty acid is linked to the amino group via an amide bond (forming a ceramide). A phosphate-containing head group is attached to the terminal hydroxyl of sphingosine. ■ Sphingomyelin: Ceramide + phosphocholine (or phosphoethanolamine). Abundant in myelin sheaths of nerve cells. (Illustration: General structure of a glycerophospholipid and sphingomyelin, highlighting amphipathic nature.)
- Glycolipids (Sphingoglycolipids): ○ Definition: Lipids containing carbohydrates, typically found on the outer leaflet of the plasma membrane. ○ Structure: Ceramide backbone with one or more sugar residues attached to the terminal hydroxyl. ○ Cerebrosides: Ceramide + single sugar (glucose or galactose). Galactocerebrosides are in neuronal membranes; glucocerebrosides elsewhere. ○ Gangliosides: Ceramide + complex oligosaccharide containing sialic acid (N-acetylneuraminic acid, NANA). Important in cell recognition, adhesion, and as receptors (e.g., for cholera toxin). GM1, GM2, GD2 are examples.
- Steroids: ○ Definition: Lipids characterized by a steroid nucleus: four fused rings (three cyclohexane rings and one cyclopentane ring). ○ Cholesterol: The most abundant steroid in animals. An essential component of cell membranes (modulates fluidity), precursor for bile acids, steroid hormones, and vitamin D. Amphipathic due to a hydroxyl group at C3. (Illustration: Structure of cholesterol and the steroid nucleus.)
sphingolipids in cells. ○ Tay-Sachs Disease: Deficiency of hexosaminidase A, accumulation of GM ganglioside. Neurodegenerative. ○ Gaucher Disease: Deficiency of glucocerebrosidase, accumulation of glucocerebroside. Affects spleen, liver, bones. ○ Niemann-Pick Disease: Deficiency of sphingomyelinase, accumulation of sphingomyelin. Affects brain, liver, spleen.
- Familial Hypercholesterolemia: Genetic disorder caused by defects in the LDL receptor, leading to very high LDL-cholesterol levels and premature atherosclerosis.
- Respiratory Distress Syndrome (RDS) in Neonates: Deficiency of pulmonary surfactant (rich in dipalmitoylphosphatidylcholine) in premature infants leads to alveolar collapse.
- Inflammation and Pain: Eicosanoids (prostaglandins, leukotrienes) are key mediators. Non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen inhibit COX enzymes.
- Steatorrhea: Presence of excess fat in feces due to malabsorption (e.g., in pancreatic insufficiency, celiac disease, bile duct obstruction).
- Ketosis/Ketoacidosis: Excessive production of ketone bodies (acetoacetate, \beta-hydroxybutyrate, acetone) from fatty acid oxidation, seen in uncontrolled diabetes mellitus or prolonged starvation.
IV. PROTEINS
Proteins are the most versatile macromolecules in living systems, performing a vast array of functions. They are polymers of amino acids linked by peptide bonds. A. Amino Acids: The Building Blocks:
- Structure: Each amino acid has a central carbon atom (\alpha-carbon) bonded to: ○ An amino group (-NH₂) ○ A carboxyl group (-COOH) ○ A hydrogen atom (-H) ○ A distinctive side chain (-R group), which determines the amino acid's properties. (Illustration: General structure of an L-amino acid.) At physiological pH (~7.4), the amino group is protonated (-NH₃⁺) and the carboxyl group is deprotonated (-COO⁻), forming a zwitterion.
- Classification (based on R group properties): ○ Nonpolar, Aliphatic (7): Glycine (Gly, G), Alanine (Ala, A), Valine (Val, V), Leucine (Leu, L), Isoleucine (Ile, I), Methionine (Met, M), Proline (Pro, P - unique imino acid). Hydrophobic, tend to be in protein interiors. ○ Aromatic (3): Phenylalanine (Phe, F), Tyrosine (Tyr, Y), Tryptophan (Trp, W). Relatively nonpolar. Tyr and Trp can absorb UV light. ○ Polar, Uncharged (5): Serine (Ser, S), Threonine (Thr, T), Cysteine (Cys, C), Asparagine (Asn, N), Glutamine (Gln, Q). Hydrophilic, can form hydrogen bonds. Cysteine can form disulfide bonds. ○ Positively Charged (Basic) (3): Lysine (Lys, K), Arginine (Arg, R), Histidine (His, H). Hydrophilic. Histidine has an imidazole group with pKa ~6, often involved in enzyme active sites. ○ Negatively Charged (Acidic) (2): Aspartate (Asp, D), Glutamate (Glu, E).
Hydrophilic. (Table: List of 20 standard amino acids with their 3-letter and 1-letter codes, and R group characteristics.)
- Essential vs. Non-Essential Amino Acids: ○ Essential (9): Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine. Must be obtained from the diet. (Mnemonic: PVT TIM HaLL) ○ Non-Essential: Can be synthesized by the body. ○ Conditionally Essential: e.g., Arginine, Glutamine, Cysteine, Tyrosine. May become essential under certain physiological conditions (e.g., illness, infancy).
- Peptide Bond: ○ Formed by a dehydration reaction between the \alpha-carboxyl group of one amino acid and the \alpha-amino group of another. ○ Has partial double-bond character, making it rigid and planar. Usually in trans configuration. ○ A series of amino acids joined by peptide bonds forms a polypeptide chain. (Illustration: Formation of a peptide bond.) B. Levels of Protein Structure: The function of a protein is dictated by its unique 3D structure.
- Primary Structure: ○ The linear sequence of amino acids in a polypeptide chain, specified by genetic information. ○ Determines all higher levels of structure. ○ Read from N-terminus (free amino group) to C-terminus (free carboxyl group).
- Secondary Structure: ○ Local, regular folding patterns of the polypeptide backbone, stabilized by hydrogen bonds between peptide bond CO and NH groups. ○ \alpha-Helix: Right-handed helical coil. H-bond between CO of residue i and NH of residue i+4. 3.6 residues per turn. Side chains project outwards. (Illustration: \alpha-helix structure.) ○ \beta-Pleated Sheet: Extended polypeptide chains (strands) aligned side-by-side. H-bonds between strands. Can be parallel (strands run in same N→C direction) or antiparallel (strands run in opposite directions). Side chains alternate above and below the sheet. (Illustration: \beta-pleated sheet structure.) ○ \beta-Turns (Reverse Turns): Short, U-shaped structures that reverse the direction of the polypeptide chain. Often connect strands of antiparallel \beta-sheets. Stabilized by H-bonds. Proline and Glycine are common in turns. ○ Loops/Coils: Irregular, non-repetitive structures connecting secondary structural elements.
- Tertiary Structure: ○ The overall three-dimensional conformation of a single polypeptide chain, resulting from interactions between the R groups of amino acids. ○ Stabilizing Forces: ■ Hydrophobic Interactions: Major driving force. Nonpolar side chains cluster in the interior, away from water. ■ Hydrogen Bonds: Between polar R groups, and between R groups and backbone atoms. ■ Ionic Bonds (Salt Bridges): Between oppositely charged R groups. ■ Disulfide Bonds (-S-S-): Covalent bonds formed by oxidation of two cysteine residues. Important for stabilizing extracellular proteins.
ubiquitin (a small protein). The ubiquitinated protein is then recognized and degraded by the proteasome (a large protein complex with proteolytic activity). ○ Lysosomal Proteolysis: Degradation of extracellular proteins, membrane proteins, and some intracellular proteins via autophagy. E. Medical and Clinical Relevance:
- Genetic Diseases due to Protein Defects: ○ Sickle Cell Anemia: Point mutation in \beta-globin gene (Glu6Val) leads to abnormal hemoglobin (HbS), causing red blood cell sickling, hemolysis, and vaso-occlusion. A classic example of how a single amino acid change can have profound structural and functional consequences. ○ Cystic Fibrosis: Mutations in the CFTR gene lead to misfolding and degradation of the CFTR protein (a chloride channel), causing defective ion transport and thick mucus secretions. ○ Phenylketonuria (PKU): Deficiency of phenylalanine hydroxylase, leading to accumulation of phenylalanine and neurotoxicity. ○ Many Enzymopathies: Genetic defects in enzymes leading to metabolic disorders.
- Protein Misfolding Diseases (Proteopathies/Amyloidosis): Characterized by the accumulation of misfolded protein aggregates. ○ Alzheimer's Disease: Extracellular plaques of amyloid-\beta (A$\beta$) peptide and intracellular neurofibrillary tangles of hyperphosphorylated tau protein. ○ Parkinson's Disease: Intraneuronal Lewy bodies containing aggregated \alpha-synuclein. ○ Prion Diseases (Transmissible Spongiform Encephalopathies): e.g., Creutzfeldt-Jakob disease (CJD), Kuru. Caused by misfolding of the prion protein (PrP$^{Sc}), which can induce misfolding of normal PrP^C$. ○ Amyloid Light-chain (AL) Amyloidosis: Deposition of misfolded immunoglobulin light chains.
- Nutritional Protein-Energy Malnutrition: ○ Kwashiorkor: Severe protein deficiency despite adequate energy intake. Characterized by edema, skin lesions, fatty liver. ○ Marasmus: Severe deficiency of both protein and calories. Characterized by extreme wasting.
- Plasma Proteins in Diagnostics: ○ Albumin: Levels can indicate liver disease, kidney disease, or malnutrition. ○ Enzymes: e.g., Creatine kinase (CK-MB) and troponins for myocardial infarction; Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) for liver damage. ○ Antibodies: Used in immunoassays for diagnosis (e.g., ELISA).
- Collagenopathies: Disorders due to defects in collagen synthesis or structure. ○ Osteogenesis Imperfecta: "Brittle bone disease," mutations in type I collagen genes. ○ Ehlers-Danlos Syndromes: Group of connective tissue disorders with joint hypermobility, skin hyperextensibility.
- Therapeutic Proteins: Many drugs are proteins or target proteins. ○ Insulin for diabetes. ○ Monoclonal antibodies for cancer, autoimmune diseases. ○ Enzyme replacement therapy for certain genetic disorders (e.g., Gaucher disease).
V. NUCLEIC ACIDS
Nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are polymers of nucleotides that store, transmit, and express genetic information. A. Structure of Nucleotides: Nucleotides are the monomeric units of nucleic acids, composed of three components:
- Nitrogenous Base: Heterocyclic aromatic compounds. ○ Purines (double-ring structure): Adenine (A), Guanine (G). ○ Pyrimidines (single-ring structure): Cytosine (C), Thymine (T, in DNA only), Uracil (U, in RNA only). (Illustration: Structures of A, G, C, T, U.)
- Pentose Sugar: A five-carbon sugar. ○ Deoxyribose (in DNA): Lacks a hydroxyl group at the 2' carbon (2'-deoxy-D-ribose). ○ Ribose (in RNA): Has a hydroxyl group at the 2' carbon (D-ribose). (Illustration: Structures of ribose and deoxyribose.) The base is linked to the 1' carbon of the sugar via an N-glycosidic bond. Base + Sugar = Nucleoside (e.g., adenosine, guanosine, cytidine, thymidine, uridine).
- Phosphate Group(s): One, two, or three phosphate groups are attached to the 5' carbon of the sugar via a phosphoester bond. ○ Nucleoside + Phosphate(s) = Nucleotide. ○ e.g., Adenosine monophosphate (AMP), Adenosine diphosphate (ADP), Adenosine triphosphate (ATP). ATP is the primary energy currency of the cell. Other nucleoside triphosphates (GTP, CTP, UTP, TTP) also have high-energy bonds and roles in metabolism and signaling. B. Deoxyribonucleic Acid (DNA):
- Structure: ○ Typically a double helix (Watson-Crick model, 1953). Two antiparallel polynucleotide strands coiled around a common axis. ○ Backbone: Alternating deoxyribose sugar and phosphate groups, linked by 3'-5' phosphodiester bonds. The phosphate group connects the 5' carbon of one sugar to the 3' carbon of the next. This gives the strand directionality (5' end and 3' end). ○ Base Pairing: The two strands are held together by hydrogen bonds between complementary bases: ■ Adenine (A) pairs with Thymine (T) via two hydrogen bonds. ■ Guanine (G) pairs with Cytosine (C) via three hydrogen bonds (stronger pairing). ■ This specific pairing (Chargaff's rules: A=T, G=C) is crucial for DNA replication and transcription. ○ The bases are stacked in the interior of the helix (hydrophobic interactions contribute to stability), while the sugar-phosphate backbones are on the outside. ○ The helix has major and minor grooves, which are sites for protein binding. (Illustration: DNA double helix structure showing backbone, base pairing, major/minor grooves, and antiparallel strands.)
- Forms of DNA: B-DNA (common physiological form), A-DNA (dehydrated form), Z-DNA (left-handed helix, may play role in gene regulation).
- Organization in Cells:
○ Point Mutations: Single base changes (substitutions, insertions, deletions). ○ Frameshift Mutations: Insertions/deletions not in multiples of three, altering the reading frame. ○ Chromosomal Abnormalities: Deletions, duplications, translocations, inversions of large DNA segments or entire chromosomes (e.g., Down syndrome - trisomy 21).
- Gene Therapy: Therapeutic delivery of nucleic acids into a patient's cells as a drug to treat disease. Aims to correct defective genes or provide new therapeutic functions.
- Infectious Diseases: ○ Viruses: Can have DNA or RNA genomes. Viral nucleic acids hijack host cell machinery for replication. (e.g., HIV - an RNA retrovirus; Herpesviruses - DNA viruses). ○ Antiviral drugs often target viral nucleic acid synthesis or viral enzymes (e.g., reverse transcriptase inhibitors for HIV, acyclovir for herpes).
- Cancer: Arises from accumulation of mutations in genes that control cell growth and division (oncogenes, tumor suppressor genes). ○ Many anticancer drugs target DNA replication or integrity (e.g., alkylating agents, topoisomerase inhibitors).
- Diagnostics and Forensics: ○ Polymerase Chain Reaction (PCR): Amplifies specific DNA sequences for detection of pathogens, genetic mutations, forensic analysis (DNA fingerprinting). ○ DNA Sequencing: Determines the exact order of nucleotides in a DNA segment. Used for diagnosing genetic disorders, personalized medicine, research. ○ Microarrays and RNA-Seq: Analyze gene expression patterns (mRNA levels) for research and diagnostics (e.g., cancer classification).
- RNA-based Therapeutics: ○ Antisense Oligonucleotides (ASOs): Short synthetic nucleic acids that bind to specific mRNA molecules to modulate gene expression (e.g., inhibit translation, alter splicing). (e.g., Nusinersen for spinal muscular atrophy). ○ siRNA/RNAi Therapeutics: Utilize RNA interference to silence disease-causing genes. ○ mRNA Vaccines: (e.g., COVID-19 vaccines by Pfizer/BioNTech and Moderna). mRNA encoding a viral antigen is delivered, and host cells produce the antigen to elicit an immune response.
- Epigenetics: Heritable changes in gene expression that do not involve alterations in the DNA sequence itself. Often involve DNA methylation (addition of methyl groups to cytosine bases, typically in CpG islands) and histone modifications, which affect chromatin structure and accessibility. Epigenetic dysregulation is implicated in cancer and other diseases.
VI. VITAMINS AND COENZYMES (Brief Overview in
Relation to Biomolecules)
Many vitamins, particularly B-complex vitamins, function as precursors for coenzymes. Coenzymes are organic non-protein molecules that are essential for the activity of many enzymes involved in the metabolism of carbohydrates, lipids, proteins, and nucleic acids. ● Thiamine (B ₁ ): Thiamine pyrophosphate (TPP) – Coenzyme in decarboxylation reactions (e.g., pyruvate dehydrogenase, \alpha-ketoglutarate dehydrogenase).
● Riboflavin (B ₂ ): Flavin adenine dinucleotide (FAD) and Flavin mononucleotide (FMN) – Coenzymes in redox reactions (electron carriers). ● Niacin (B ₃ ): Nicotinamide adenine dinucleotide (NAD⁺) and Nicotinamide adenine dinucleotide phosphate (NADP⁺) – Coenzymes in redox reactions (electron carriers). ● Pantothenic Acid (B ₅ ): Component of Coenzyme A (CoA) – Carrier of acyl groups (e.g., in fatty acid metabolism, citric acid cycle). ● Pyridoxine (B ₆ ): Pyridoxal phosphate (PLP) – Coenzyme in amino acid metabolism (transamination, decarboxylation). ● Biotin (B ₇ ): Coenzyme in carboxylation reactions. ● Folate (B ₉ ): Tetrahydrofolate (THF) – Coenzyme in transfer of one-carbon units (e.g., in synthesis of purines, thymidine, methionine). ● Cobalamin (B ₁₂ ): Coenzyme in methionine synthesis and isomerization of methylmalonyl-CoA. ● Vitamin C (Ascorbic Acid): Coenzyme for prolyl and lysyl hydroxylases (collagen synthesis), antioxidant. ● Fat-soluble vitamins (A, D, E, K): Have diverse roles often related to lipid metabolism, signaling, or membrane function (e.g., Vitamin K in carboxylation of glutamate residues in clotting factors). Deficiencies in these vitamins impair the function of enzymes critical for biomolecule processing, leading to various metabolic disorders and clinical manifestations.
VII. TECHNIQUES IN MEDICAL BIOCHEMISTRY FOR
BIOMOLECULE ANALYSIS (Brief Overview)
The study and clinical assessment of biomolecules rely on a wide array of analytical techniques:
- Spectrophotometry: Measures absorption or transmission of light by biomolecules (e.g., protein concentration using Bradford or Lowry assays, enzyme activity by monitoring substrate/product absorbance). UV absorbance at 260 nm for nucleic acids, 280 nm for proteins.
- Chromatography: Separates biomolecules based on differences in size, charge, hydrophobicity, or binding affinity. ○ High-Performance Liquid Chromatography (HPLC): Widely used for analysis of amino acids, peptides, proteins, carbohydrates, nucleotides, drugs. ○ Gas Chromatography (GC): For volatile compounds, often coupled with Mass Spectrometry (GC-MS) for fatty acid analysis, drug screening. ○ Ion-Exchange Chromatography: Separates based on net charge. ○ Size-Exclusion (Gel Filtration) Chromatography: Separates based on molecular size. ○ Affinity Chromatography: Separates based on specific binding interactions (e.g., antibody-antigen, enzyme-substrate).
- Electrophoresis: Separates biomolecules (proteins, nucleic acids) based on their migration in an electric field, usually through a gel matrix (agarose or polyacrylamide). Separation by size, charge, or shape. ○ SDS-PAGE (Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis): Separates proteins primarily by mass. ○ Isoelectric Focusing (IEF): Separates proteins based on their isoelectric point (pI). ○ Agarose Gel Electrophoresis: Separates DNA and RNA fragments by size.
