Biochemistry: Metabolism

• Biochemistry explores the chemical processes within and related to living organisms
• It combines biology and chemistry to study the structures, functions, and interactions of biological molecules

Metabolism

• Metabolism involves life-sustaining chemical transformations within cells
• These processes facilitate organismal growth, reproduction, structural maintenance, and environmental response
• Catabolism and anabolism are the broad categories of metabolism
• Catabolism is the breakdown of molecules releasing energy
• Anabolism is the synthesis of molecules requiring energy
• Metabolic pathways are interconnected biochemical reactions
• Enzymes catalyze reactions ensuring specificity and efficiency
• ATP (adenosine triphosphate) is the main energy currency driving metabolic processes
• Glycolysis converts glucose into pyruvate
• The citric acid cycle (Krebs cycle) oxidizes acetyl-CoA, yielding energy carriers like NADH and FADH2
• Oxidative phosphorylation uses the electron transport chain to produce a proton gradient for ATP synthesis
• Photosynthesis converts light energy chemical energy in plants, and some other organisms
• Gluconeogenesis synthesizes glucose from non-carbohydrate precursors
• The pentose phosphate pathway produces NADPH and pentose sugars
• Fatty acid synthesis creates fatty acids using acetyl-CoA and NADPH
• Beta-oxidation breaks down fatty acids to produce acetyl-CoA, NADH, and FADH2
• The urea cycle converts toxic ammonia, a byproduct of amino acid metabolism, into urea for excretion

Enzyme Kinetics

• Enzyme kinetics studies the rates of enzyme-catalyzed reactions
• Enzymes are biological catalysts that accelerate reactions without being consumed
• Substrates are the molecules enzymes act upon
• The active site is where substrate binds and catalysis occurs on an enzyme
• The Michaelis-Menten equation relates initial reaction rate (v0), maximum reaction rate (Vmax), Michaelis constant (Km), and substrate concentration ([S]): v0 = (Vmax * [S]) / (Km + [S])
• Vmax is the maximum reaction rate when the enzyme is saturated with substrate
• Km is the substrate concentration at half Vmax, reflecting enzyme affinity for the substrate. Low Km indicates high affinity, and high Km indicates low affinity
• Enzyme inhibitors reduce or prevent enzyme activity
• Competitive inhibitors bind to the active site, preventing substrate binding
• Non-competitive inhibitors bind to a different site, altering enzyme shape and reducing activity
• Uncompetitive inhibitors bind only to the enzyme-substrate complex
• Allosteric enzymes have multiple binding sites and exhibit cooperativity
• Enzyme activity is affected by temperature, pH, cofactors, and coenzymes
• Cofactors are inorganic ions or organic molecules needed for enzyme activity
• Coenzymes are organic cofactors, often vitamin-derived

Genetic Regulation

• Genetic regulation controls gene expression: the transcription of genes into RNA and their translation into proteins
• Gene expression is regulated at levels like transcription, RNA processing, translation, and post-translational modification
• Transcription factors are proteins that bind to DNA and regulate transcription; activators enhance it, and repressors inhibit it
• Promoters are DNA sequences where RNA polymerase binds to start transcription
• Enhancers are DNA sequences that increase transcription from a distance
• Silencers are DNA sequences that repress transcription from a distance
• Operons are gene clusters transcribed together under a single promoter, commonly in bacteria
• The lac operon in E. coli controls genes for lactose metabolism
• In the absence of lactose, a repressor protein binds to the operator, preventing transcription.
• Lactose presence causes it to bind the repressor, detaching it from the operator and allowing transcription
• The trp operon in E. coli regulates genes for tryptophan synthesis
• Tryptophan abundance causes it to bind a repressor protein, which binds the operator, inhibiting transcription
• Epigenetics involves heritable gene expression changes without DNA sequence alteration
• DNA methylation, the addition of methyl groups to DNA, is often linked to transcriptional repression
• Histone modification involves changes to histone proteins, affecting chromatin structure and gene expression
• Non-coding RNAs like microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are key in gene regulation

Cell Signaling

• Cell signaling is communication between cells or between a cell and its environment
• Signals can be chemical (hormones, neurotransmitters, growth factors) or physical (light, mechanical stimuli)
• Reception is how a cell detects a signal
• Receptors are proteins that bind to signaling molecules and initiate responses
• A ligand is a molecule that binds to a receptor
• Signal transduction converts a signal into a cellular response
• Signaling pathways amplify and relay signals through molecular events
• Common pathways include G protein-coupled receptor (GPCR), receptor tyrosine kinase (RTK), and steroid hormone receptor pathways
• GPCRs are transmembrane receptors that activate G proteins upon ligand binding
• G proteins activate downstream effectors like enzymes or ion channels
• RTKs are transmembrane receptors that activate intracellular signaling pathways upon ligand binding and receptor dimerization
• Second messengers like cAMP, IP3, and calcium ions amplify and spread signals within the cell
• Cellular responses include changes in gene expression, metabolism, cell shape, or cell movement
• Termination of the signal prevents overstimulation and maintains proper cellular function

Protein Structure

• Proteins are biomolecules with polypeptide chains
• They perform various functions: catalysis, transport, structure, and signaling
• Amino acids are protein building blocks, linked by peptide bonds
• A polypeptide chain is a linear sequence of amino acids
• The primary structure is the amino acid sequence
• The secondary structure involves local folding like alpha-helices and beta-sheets
• Alpha-helices are coiled, stabilized by hydrogen bonds
• Beta-sheets are extended, formed by hydrogen bonds between strands
• The tertiary structure is the overall 3D shape set by side chain interactions like hydrophobic interactions, hydrogen bonds, ionic bonds, and disulfide bridges
• The quaternary structure is the arrangement of multiple polypeptide chains in a multi-subunit protein
• Protein folding is how a polypeptide chain gets its 3D structure
• Chaperone proteins aid folding, preventing aggregation and misfolding
• Protein misfolding can cause diseases like Alzheimer's and Parkinson's
• Domains are distinct structural and functional regions within a protein
• Protein purification techniques like chromatography and electrophoresis isolate and study proteins
• X-ray crystallography and NMR spectroscopy determine 3D protein structures