The guanosine triphosphate-binding proteins (G proteins) found in a variety of tissues transduce signals generated by ligand binding to cell surface receptors into changes in intracellular metabolism. Amino acid sequences of peptides prepared by partial proteolysis of the alpha subunit of a bovine brain G protein and the alpha subunit of rod outer-segment transducin were determined. The two proteins show regions of sequence identity as well as regions of diversity. A portion of the amino-terminal peptide sequence of each protein is highly homologous with the corresponding region in the ras protein (a protooncogene product). These similarities suggest that G proteins and ras proteins may have analogous functions.

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The metabolism of coenzyme A and control of its synthesis are reviewed. Pantothenate kinase is an important rate-controlling enzyme in the synthetic pathway of all tissues studied and appears to catalyze the flux-generating reaction of the pathway in cardiac muscle. This enzyme is strongly inhibited by coenzyme A and all of its acyl esters. The cytosolic concentrations of coenzyme A and acetyl coenzyme A in both liver and heart are high enough to totally inhibit pantothenate kinase under all conditions. Free carnitine, but not acetyl carnitine, deinhibits the coenzyme A-inhibited enzyme. Carnitine alone does not increase enzyme activity. Thus changes in the acetyl carnitine-to-carnitine ratio that occur with nutritional states provides a mechanism for regulation of coenzyme A synthetic rates. Changes in the rate of coenzyme A synthesis in liver and heart occurs with fasting, refeeding, and diabetes and in heart muscle with hypertrophy. The pathway and regulation of coenzyme A degradation are not understood.

The G protein ␤␥-dimer is required for receptor interaction and effector regulation. However, previous approaches have not identified the physiologic roles of individual subtypes in these processes. We used a gene knockout approach to demonstrate a unique role for the G protein ␥ 7 -subunit in mice. Notably, deletion of Gng7 caused behavioral changes that were associated with reductions in the ␣ olf -subunit content and adenylyl cyclase activity of the striatum. These data demonstrate that an individual ␥-subunit contributes to the specificity of a given signaling pathway and controls the formation or stability of a particular G protein heterotrimer.The heterotrimeric G proteins control diverse biological processes by conveying signals from cell-surface receptors to intracellular effectors. Although function was originally ascribed to the GTP-bound ␣-subunit, it is now well established that the ␤␥-dimer plays active roles in the signaling process through upstream recognition of receptors and downstream regulation of effectors (1). Molecular cloning has identified at least 5 ␤-and 12 ␥-subunit genes in the mouse and human genomes. Structurally, ␥-subunits are the most diverse, with four subgroups that show less than 50% identity to each other (2). Moreover, ␥-subunits exhibit very different temporal (3, 4) and spatial (5) patterns of expression. These characteristics suggest that ␥-subunits have heterogeneous functions. However, comparison of their biochemical properties has revealed only modest differences (6 -8), perhaps because of the inherent limitations of transfection and reconstitution approaches. Gene ablation in mice has proven to be a powerful approach to identifying the functional roles of several G protein ␣-subunits (9). We report the first use of a gene targeting strategy to identify a unique function for a member of the ␥-subunit family.The G protein ␥ 7 -subunit (G␥ 7 ) was originally cloned from bovine brain (10). In situ hybridization of rat brain sections revealed that mRNA for G␥ 7 is most highly expressed in the striatum (5), where it is found in 40 -50% of medium sized neurons in the caudate putamen (11). The regional expression of mRNA for G␥ 7 in the brain mirrors that of the striatumenriched D 1 dopamine receptor (D1R), 1 G␣ olf , and adenylyl cyclase Type V (12), suggesting involvement of G␥ 7 in the G␣ olf -mediated stimulation of adenylyl cyclase by dopamine. Single cell RT-PCR analysis confirms that D1R and G␥ 7 are expressed in the same subset of rat neurons (13). Ribozyme suppression studies support a role for G␥ 7 in the endogenous ␤-adrenergic receptor pathway (14) and the heterologously expressed D1R pathway in human embryonic kidney cells (13).

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