Metabolic organization: anabolism/catabolism, energy currencies, coupled reactions, regulation.
Metabolism Overview
Metabolism
The sum of enzyme-catalysed reactions in a cell — catabolism (breakdown releasing energy) plus anabolism (biosynthesis consuming energy).…
Anabolism
Endergonic biosynthetic arm of metabolism: building macromolecules from precursors, powered by ATP hydrolysis and NADPH reducing…
Catabolism
Exergonic degradative arm of metabolism: breakdown of macromolecules releasing energy captured as ATP and NADH.
ATP/ADP cycle
Principal energy currency of the cell: ATP hydrolysis (ΔG°' ≈ −30.5 kJ/mol) drives endergonic reactions; ADP is rephosphorylated by…
NAD+/NADH cycle
Primary electron carrier of catabolism (ΔE°' = −0.32 V). NAD+ is reduced to NADH during substrate oxidation; NADH is reoxidised at ETC…
Reducing equivalent
Currency of biological reduction reactions: NADH and NADPH carry hydride (H−) to reduction steps; NADH drives catabolism, NADPH drives…
Substrate-level phosphorylation
Direct transfer of a phosphate group from a high-energy metabolic intermediate to ADP. Examples: phosphoglycerate kinase, pyruvate kinase,…
Metabolic flux
Rate of material flow through a metabolic pathway (mol·s⁻¹). Measured by 13C-MFA + FBA; set by enzyme levels, cofactor availability,…
Metabolic control analysis
Kacser-Burns / Heinrich-Rapoport 1973-74 theory: flux control is distributed across enzymes, quantified by flux-control coefficients C^J_i…
Feedback inhibition
Pathway end-product allosterically inhibits the committed enzyme (first irreversible step), preventing overproduction. Classic: CTP…
Flux-balance analysis (FBA) framework
Stoichiometric matrix S (m×n) of an organism encodes mass-balance constraints S·v = 0 at steady state. Linear-programming maximises a…
Metabolic control analysis (MCA) framework
Kacser-Burns / Heinrich-Rapoport 1973-74: flux-control coefficients C_i^J = (∂J/∂E_i) · (E_i/J) sum to 1 across the pathway (summation…
Krebs cycle (1937)
H Krebs 1937 (Nobel 1953) citric-acid-cycle; foundational text in biochemistry; modern Warburg-effect + glutaminolysis variants.
Glycolysis foundation
Embden-Meyerhof-Parnas 1930s 10-step glucose -> 2 pyruvate; +2 ATP; basis of all cellular bioenergetics.
PPP foundation
Warburg-Dickens 1933 + Horecker-Lipmann 1950s pentose-phosphate-pathway; NADPH + R5P; biosynthesis foundation.
13C MFA (Wiechert 2001)
Wiechert 2001 + Antoniewicz 2018 13C-MFA isotope-tracer metabolic-flux-analysis; modern systems-biology workflow.
MCA (Kacser-Burns 1973)
Kacser-Burns 1973 + Heinrich-Rapoport 1974 metabolic-control-analysis; flux-control-coefficients sum to 1; modern engineered-microbes.
Warburg effect (1924)
O Warburg 1924 (Nobel 1931) cancer-metabolism aerobic-glycolysis; modern HIF-1alpha + LDH-targets in chemotherapy.
Metabolic network (Jeong 2000)
Jeong-Tombor-Albert-Oltvai-Barabasi 2000 metabolic-network scale-free; modern Recon-3D human + iJO1366 E coli.
Metabolomics (Fiehn 2002)
O Fiehn 2002 metabolic-fingerprinting; modern HILIC-MS + GC-MS + NMR + Metabolon + HMDB 200000+ metabolites.
13C tracing (Antoniewicz 2018)
M Antoniewicz 2018 + Wiechert 2001 13C-MFA; modern systems-biology + cancer + microbial-engineering.
Warburg + cancer-metabolism
Warburg 1924 + Vander-Heiden 2009 'Understanding the Warburg effect'; modern PI3K-Akt-mTOR + HIF-1alpha.
Ketosis (Cahill 1976)
G Cahill 1976 ketogenic-state; modern keto-diet + intermittent-fasting + AMPK/mTOR + brain BHB-fuel.
NAD+ aging (Imai-Guarente 2014)
Imai-Guarente 2014 NAD+ + sirtuin metabolism; modern NMN + NR supplements; clinical-trials longevity.
Heinrich-Rapoport summation theorem of metabolic control analysis
Heinrich-Rapoport summation theorem (Heinrich-Rapoport 1974 *Eur J Biochem* 42, 89; co-discovered by Kacser-Burns 1973 *Symp Soc Exp Biol*…