Bioenergetic scaling: metabolic design and body-size constraints in mammals.

The cytosolic phosphorylation ratio ([ATP]/[ADP][P(i)]) in the mammalian heart was found to be inversely related to body mass with an exponent of -0.30 (r = 0.999). This exponent is similar to -0.25 calculated for the mass-specific O2 consumption. The inverse of cytosolic free [ADP], the Gibbs energy of ATP hydrolysis (delta G'ATP), and the efficiency of ATP production (energy captured in forming 3 mol of ATP per cycle along the mitochondrial respiratory chain from NADH to 1/2 O2) were all found to scale with body mass with a negative exponent. On the basis of scaling of the phosphorylation ratio and free cytosolic [ADP], we propose that the myocardium and other tissues of small mammals represent a metabolic system with a higher driving potential (a higher delta G'ATP from the higher [ATP]/[ADP][P(i)]) and a higher kinetic gain [(delta V/Vmax)/delta [ADP]] where small changes in free [ADP] produce large changes in steady-state rates of O2 consumption. From the inverse relationship between mitochondrial efficiency and body size we calculate that tissues of small mammals are more efficient than those of large mammals in converting energy from the oxidation of foodstuffs to the bond energy of ATP. A higher efficiency also indicates that mitochondrial electron transport is not the major site for higher heat production in small mammals. We further propose that the lower limit of about 2 g for adult endotherm body size (bumblebee-bat, Estrucan shrew, and hummingbird) may be set by the thermodynamics of the electron transport chain. The upper limit for body size (100,000-kg adult blue whale) may relate to a minimum delta G'ATP of approximately 55 kJ/mol for a cytoplasmic phosphorylation ratio of 12,000 M-1.

Versatile 5′ phosphoryl coupling of small and large molecules to an RNA

A Ca2+-requiring catalytic RNA is shown to create 5′ phosphate–phosphate linkages with all nucleotides and coenzymes including CoA, nicotinamide adenine dinucleotide phosphate, thiamine phosphate, thiamine pyrophosphate, and flavin mononucleotide. In addition to these small molecules, macromolecules such as RNAs with 5′-diphosphates, and nonnucleotide molecules like Nɛ-phosphate arginine and 6-phosphate gluconic acid also react. That is, the self-capping RNA isolate 6 is an apparently universal 5′ phosphate-linker, reacting with any nucleophile containing an unblocked phosphate. These RNA reactions demonstrate a unique RNA catalytic capability and imply versatile and specific posttranscriptional RNA modification by RNA catalysis.

c-Myc enhances protein synthesis and cell size during B lymphocyte development

Members of the myc family of nuclear protooncogenes play roles in cell proliferation, differentiation, and apoptosis. Moreover, inappropriate expression of c-myc genes contributes to the development of many types of cancers, including B cell lymphomas in humans. Although Myc proteins have been shown to function as transcription factors, their immediate effects on the cell have not been well defined. Here we have utilized a murine model of lymphomagenesis (Eμ-myc mice) to show that constitutive expression of a c-myc transgene under control of the Ig heavy-chain enhancer (Eμ) results in an increase in cell size of normal pretransformed B lymphocytes at all stages of B cell development. Furthermore, we show that c-Myc-induced growth occurs independently of cell cycle phase and correlates with an increase in protein synthesis. These results suggest that Myc may normally function by coordinating expression of growth-related genes in response to mitogenic signals. Deregulated c-myc expression may predispose to cancer by enhancing cell growth to levels required for unrestrained cell division.

Invariant scaling relationships for interspecific plant biomass production rates and body size

The allometric relationships for plant annualized biomass production (“growth”) rates, different measures of body size (dry weight and length), and photosynthetic biomass (or pigment concentration) per plant (or cell) are reported for multicellular and unicellular plants representing three algal phyla; aquatic ferns; aquatic and terrestrial herbaceous dicots; and arborescent monocots, dicots, and conifers. Annualized rates of growth G scale as the 3/4-power of body mass M over 20 orders of magnitude of M (i.e., G ∝ M3/4); plant body length L (i.e., cell length or plant height) scales, on average, as the 1/4-power of M over 22 orders of magnitude of M (i.e., L ∝ M1/4); and photosynthetic biomass Mp scales as the 3/4-power of nonphotosynthetic biomass Mn (i.e., Mp ∝ Mn3/4). Because these scaling relationships are indifferent to phylogenetic affiliation and habitat, they have far-reaching ecological and evolutionary implications (e.g., net primary productivity is predicted to be largely insensitive to community species composition or geological age).