Metabolism Concepts

• BCHEM 253 is related to metabolism in both health and diseases.
• The course is taught by Dr. Christopher Larbie at Kwame Nkrumah University of Science and Technology, Kumasi.
• Metabolism defines the biological processes by which living systems use free energy to perform functions.
• Metabolism requires highly coordinated cellular activity and performs four functions:
• Obtaining energy for the cell
• Converting nutrients into macromolecules
• Assembling macromolecules into cellular structures
• Degrading macromolecules for biological functions
• All reactions concerned with the generation, storage, and utilization of metabolic energy are intermediary metabolism.
• Energy metabolism consists of pathways that store or generate metabolic energy; it is also called bioenergetics.
• Secondary metabolism involves specialized products required by cells in small amounts, like the biosynthesis of hormones and plant pigments.
• Atoms form molecules, which form cells, which form tissues, which form organs, which form organ systems and organisms.
• Biomolecules of life exist as both organic and inorganic molecules.
• Organic molecules:
• Carbohydrates are energy-rich and play a role in cellular respiration and structure, and are composed of simple sugars (monosaccharides)
• Lipids consist of fatty acids and glycerol, and helps in cell membrane structure, and are composed of fatty acids and glycerol
• Water is the location for chemical reactions
• Proteins contain C, H, O, and N, function as enzymes, have structural roles, act as carriers, e.g. hemoglobin
• Nucleic acids, DNA and RNA, contain C, H, O, N, and P, and are the building blocks for nucleotides
• Nitrogen forms protein and nucleic acids.
• How cells obtain energy (carbon sources):
• Photoautotrophs obtain energy from light, using inorganic substances to produce organic compounds
• Photoheterotrophs obtain energy from light, using organic substances to produce energy
• Chemoautotrophs obtain energy from inorganic oxidation, converting it to organic compounds
• Chemoheterotrophs also extract energy/carbon from organic compounds from other organisms
• Various organisms require differing levels of oxygen:
• Aerobic organisms need high concentrations of oxygen
• Microaerophilic organisms need little amounts of oxygen
• Facultative anaerobic organisms do not require oxygen to survive
• Aerotolerant anaerobic organisms do not get poisoned or require oxygen for survival
• Anaerobic organisms cannot survive in the presence of oxygen

Why Study Metabolism?

• Living organisms transform energy to do cellular work.
• The source of energy for all living organisms is the sun’s energy.
• Cells cannot use heat for work unless it is transferred between two bodies at different temperatures.
• Cells transform heat energy into chemical forms to perform work.

Metabolic Pathway Characteristics

• A metabolic pathway is a series of connected enzymatic reactions that produce a specific product.
• Pathways are sequences of reactions, including:
• Linear pathways where the series of reactions are independent
• Cyclic pathways where the intermediates are regenerated at every turn
• Spiral pathways where the same set of enzymes are used repeatedly
• A metabolon is a temporary structural-functional complex formed between sequential enzymes of a metabolic pathway.
• The formation of metabolons allows intermediate products to be directly passed to the next enzyme in the pathway.

Metabolic Pathways Relation

• They are irreversible and exergonic which gives the patway direction
• They have a first committed step
• They are highly regulated, regulating metabolic flux of metabolites, often beginning with the first committed step of the system
• They occur in eukaryotes and occur in specific cellular molecules
• There are specific organelles for particular processes:
• Mitochondria - Citric acid cycle, oxidative phosphorylation, amino acid catabolism, fatty acid oxidation
• Cytosol – Glycolysis, pentose phosphate pathway, fatty acid biosynthesis, gluconeogenesis
• Nucleus - DNA replication and RNA transcription
• Golgi apparatus – Post translational modification of membrane and secretory proteins, formation of plasma membranes and secretory vesicles
• Rough Endoplasmic Reticulum – Synthesis of membrane-bound and secretory proteins
• Smooth Endoplasmic Reticulum – Lipid and steroid biosynthesis
• Peroxisomes - Oxidative reactions involving amino acid oxidases and catalase, glyoxylate cycle reactions in plants

Principal Metabolic Reactions

• Oxidation-reduction reactions are essential and catalyzed by oxidorectases or dehydrogenases.
• Ligation reactions form bonds by using free energy from ATP cleavage.
• Isomerization reactions rearrange atoms and are catalyzed by isomerases or epimerases.
• Group-transfer reactions transfer a phosphoryl group from ATP to glucose, catalyzed by kinases.
• Hydrolytic reactions cleave bonds with water, catalyzed by hydrolases.
• The addition of functional groups to double bonds, or the the removal of groups to form double bonds are catatlyzed by lyases

Metabolic Control Mechanism

• The major control for metabolic activities are linked to enzyme levels (lac Operon in E coli).
• Enzyme activity is controlled by:
• Allosterism (allosteric inhibiton and activation)
• Covalent modification of enzymes (phosphorylation cascade enzymes)
• Compartmentation of enzyme activity
• Hormonal regulation also plays a role in metablic control:
• Steroid Hormones (glucocorticoids, mineralcorticoids, androgens, and estrogens)
• Non-Steroidal Hromones (e.g glucagon)

Experimental Analysis of Metabolic Pathways

• Experimental approaches:
• Cell-free systems
• Whole cells
• Cellular systems (in vivo)
  • Whole Cells
  • FACS
• Cell Culture
• Tissue Slices
• Isolated or prefused organs
  • Using Whole Organisms
  • Isotopic labeling and Monitoring
  • Sacrificing
  • Biopsy
  • NMR
  • Use of Unicellular animals
• Metabolic inhibitors are also use.