Chapter 15

Fundamental Reasons Energy is Needed

• Energy is needed for mechanical work, active transport, and synthesis of biomolecules.
• Energy is obtained from the environment via phototrophs, which use photosynthesis to get energy from sunlight.
• Chemotrophs obtain energy from the oxidation of carbon molecules.

Metabolic Reactions

• Metabolism involves linked chemical reactions converting biomolecules, without harmful byproducts.
• Pathways are interdependent, coordinated by allosteric enzymes.
• Catabolism converts fuel energy into useful forms, like ATP or ion gradients.
• Anabolism requires energy input to synthesize molecules like glucose, fats, or DNA.
• Amphibolic pathways can be anabolic or catabolic based on the cell’s energy conditions and have unique regulated or irreversible reactions.

Criteria for a Metabolic Pathway

• Individual reactions must be specific and yield only one product or a set of products.
• The entire set of reactions in a pathway must be thermodynamically favorable with an overall negative free energy change.
• Unfavorable reactions can couple with favorable ones.

Carbon Oxidation & Energy

• Carbon oxidation is paired with reduction, regenerating ATP from ADP and P₁.
• Redox reactions involve oxidation (loss of electrons) and reduction (gain of electrons).
• Oxygen is the final electron acceptor in carbon oxidation, producing carbon dioxide.
• The energy is trapped in high-phosphoryl-transfer-potential compounds, used to form ATP via substrate-level phosphorylation.

Recurring Motifs

• ATP is an activated carrier of phosphoryl groups.
• Transfer of phosphoryl groups is energetically favorable or exergonic.
• ATP drives thermodynamically unfavorable reactions, alters energy or conformation, and/or alters protein activity.
• Pyridine nucleotides or flavins are the initial electron acceptors from fuel molecules.
• Electrons ultimately transfer to O₂, which has a high electron affinity creating a more stable configuration.
• The energy released from electron transfer is used to make ATP.
• Nicotinamide adenine dinucleotide (NAD+) is a pyridine nucleotide where the nicotinamide ring accepts a hydrogen ion and two electrons, forming NADH.
• NADH is synthesized from the vitamin niacin, and is equivalent to a hydride ion (H-); another proton appears in solution, and a dehydrogenation reaction occurs.
• Flavin adenine dinucleotide (FAD) is where the isoalloxazine ring accepts two electrons and two protons to form FADH₂ deriving from vitamin riboflavin

Activated Carriers of Electrons

• In addition to ATP, high potential electrons are required in anabolic reactions.
• Nicotinamide Adenine Dinucleotide Phosphate (NADPH)is an electron donor in most reductive biosynthesis; different from NADH by a 2'-hydroxyl group on adenosine which is esterified with phosphate.
• It helps enzymes recognize high potential electrons used in anabolism.

Two Carbon Fragments and Coenzyme A

• Coenzyme A carries acyl groups in both catabolism and anabolism.
• The reactive site is the terminal sulfhydryl group; acyl groups are linked via thioester bonds, forming acyl CoA and often is an acetyl group, making acetyl CoA.
• Transfer of the acetyl group is thermodynamically favorable and exergonic.

Molecule Stability

• Molecules need enzymes to control free energy flow, reducing power, NADH, NADPH, and FADH₂ react slowly with O₂ without an enzyme.
• ATP and acetyl CoA hydrolyze slowly without an enzyme.
• A small subset of carriers participates in interchanges of activated groups, acting as a unifying motif in biochemistry.

Metabolic Processes

• Important to maintain a relatively stable internal environment.
• Controlling the amounts of enzymes, catalytic activity, and the accessibility of the substrates regulates metabolism.
• The amount of enzymes depends on Rate of synthesis which is Regulation of gene transcription and Rate of degradation.

Catalytic Activity

• Allosteric control includes feedback inhibition, and reversible covalent modifications.
• Hormones coordinate metabolic reactions through reversible covalent modifications, primarily regulated by messengers like cAMP and calcium ions.
• Energy status of the cell uses energy charge and phosphorylation potential.
• Energy charge is [ATP] + ½[ADP] / [ATP] + [ADP] + [AMP].
  • An energy charge of 0 means all AMP, 1 means all ATP.
  • High energy charge favors anabolic pathways, and anything less than 0.9 favors catabolic, so its typically maintained between 0.80-0.95.
• Phosphorylation Potential is [ATP] / [ADP] + [P], and depends on concentration of inorganic phosphate.

Accessibility of Substrates

• Access requires a signal.
  • Insulin causes insertion of glucose transporters into the plasma membrane of cells, meaning Glucose can only enter cells when insulin is present.
• Anabolic and catabolic reactions take place in different areas or organelles of the cells.