Metabolism - the entire network of chemicalreactions carried out by living cells. Metabolism also includes coordination, regulation and energy requirement. • Metabolites - small molecule intermediates in the degradation and synthesis of polymers Most organism use the same general pathway for extraction and utilization of energy. All living organisms are divided into two major classes: Autotrophs – can use atmospheric carbon dioxide as a sole source of carbon for the synthesis of macromolecules. Autotrophs use the sun energy for biosynthetic purposes. Heterotrophs – obtain energy by ingesting complex carbon-containing compounds. Heterotrophs are divided into aerobs and anaerobs.
Common features of organisms 1. Organisms or cells maintain specific internal concentrations of inorganic ions, metabolites and enzymes 2. Organisms extract energy from external sources to drive energy-consuming reactions 3. Organisms grow and reproduce according to instructions encoded in the genetic material 4. Organisms respond to environmental influences 5. Cells are not static, and cell components arecontinually synthesized and degraded (i.e. undergo turnover)
A sequence of reactions that has a specific purpose (for instance: degradation of glucose, synthesis of fatty acids) is called metabolic pathway. Metabolic pathway may be: (c) Spiral pathway (fatty acid biosynthesis) (a) Linear (b) Cyclic
Metabolic pathways can be grouped into two paths – catabolismandanabolism Catabolic reactions - degrademolecules to create smaller molecules and energy Anabolic reactions - synthesize molecules for cell maintenance, growth and reproduction Catabolism is characterized by oxidation reactions and by release of free energy which is transformed to ATP. Anabolism is characterized by reduction reactions and by utilization of energy accumulated in ATP molecules. Catabolism and anabolismare tightly linked together by their coordinated energy requirements: catabolic processes release the energy from food and collect it in the ATP; anabolic processes use the free energy stored in ATP to perform work.
Metabolism Proceeds by Discrete Steps Single-step vs multi-step pathways • Multiple-steppathways permit control of energy input and output • Catabolic multi-step pathways provide energy in smallerstepwiseamounts • Each enzyme in a multi-step pathway usually catalyzes only one single step in the pathway • Controlpoints occur in multistep pathways A multistep enzyme pathway releases energy in smaller amounts that can be used by the cell
Metabolic Pathways Are Regulated • Metabolism is highlyregulated to permit organisms to respond to changing conditions • Most pathways are irreversible • Flux - flow of material through a metabolic pathway which depends upon: (1) Supply of substrates (2) Removal of products (3) Pathway enzyme activities
Levels of Metabolism Regulation • Nervous system. • Endocrine system. • Interaction between organs. • Cell (membrane) level. • Molecular level
Feedback inhibition • Product of a pathway controls the rate of its own synthesis by inhibiting an early step (usually the first “committed” step (unique to the pathway) Feed-forward activation • Metabolite early in the pathway activates an enzyme further down the pathway
Covalent modification for enzyme regulation • Interconvertible enzyme activity can be rapidly and reversibly altered by covalentmodification • Protein kinases phosphorylate enzymes (+ ATP) • Protein phosphatases remove phosphoryl groups
Regulatory role of a protein kinase, amplification by a signaling cascade The initial signal may be amplified by the “cascade” nature of this signaling
Stages of metabolism Catabolism Stage I. Breakdown of macromolecules (proteins, carbohydrates and lipids to respective building blocks. Stage II. Amino acids, fatty acids and glucose are oxidized to common metabolite (acetyl CoA) Stage III. Acetyl CoA is oxidized in citric acid cycle to CO2 and water. As result reduced cofactor, NADH2 and FADH2, are formed which give up their electrons. Electrons are transported via the tissue respiration chain and released energy is coupled directly to ATP synthesis.
Catabolism is characterized by convergence of three major routs toward a final common pathway. Different proteins, fats and carbohydrates enter the same pathway – tricarboxylic acid cycle. Anabolism can also be divided into stages, however the anabolic pathways are characterized by divergence. Monosaccharide synthesis begin with CO2, oxaloacetate, pyruvate or lactate.Amino acids are synthesized from acetyl CoA, pyruvate or keto acids of Krebs cycle. Fatty acids are constructed from acetyl CoA. On the next stage monosaccharides, amino acids and fatty acids are used for the synthesis of polysaccharides, proteins and fats.
Compartmentation of Metabolic Processes in Cell • Compartmentation of metabolic processes permits: • - separate pools of metabolites within a cell • - simultaneous operation of opposing metabolic paths • - high local concentrations of metabolites • Example: fatty acid synthesis enzymes (cytosol), fatty acid breakdown enzymes (mitochondria)
The chemistry of metabolism • There are about 3000 reactions in human cell. • All these reactions are divided into six categories: • Oxidation-reduction reactions • Group transfer reactions • Hydrolysis reactions • Nonhydrolytic cleavage reactions • Isomerization and rearrangement reactions • Bond formation reactions using energy from ATP
1.Oxidation-reduction reactions Oxidation-reduction reactions are those in which electrons are transferred from one molecule or atom to another Enzymes: oxidoreductases • oxidases - peroxidases - dehydrogenases -oxigenases Coenzymes: NAD+, NADP+, FAD+, FMN+ Example:
2.Group transfer reactions Transfer of a chemical functional group from one molecule to another (intermolecular) or group transfer within a single molecule (intramolecular) Enzymes: transferases Examples: Phosphorylation Acylation Glycosylation
3.Hydrolysis reactions • Water is used to split the single molecule into two molecules Enzymes: hydrolases - esterases - peptidases - glycosidases Example:
4.Nonhydrolytic cleavage reactions • Split or lysis of a substrate, generating a double bond in a nonhydrolytic (without water), nonoxidative elimination Enzymes: lyases Example:
5. Isomerization and rearrangement reactions Two kinds of chemical transformation: 1. Intramolecular hydrogen atom shifts changing the location of a double bond. 2. Intramolecular rearrangment of functional groups. Enzymes: isomerases Example:
6. Bond formation reactions using energy from ATP • Ligation, or joining of two substrates • Require chemical energy (e.g. ATP) Enzymes: ligases (synthetases)