This is the first of four chapters focusing on reactive intermediates accessible to organic substrates under physiologic conditions in the active sites of specific enzyme catalysts. This chapter focuses on carbanions as carbon nucleophiles. Enolates of pyruvate and thioester enolates of the acetyl group of acetyl coenzyme A are two common carbon nucleophiles. The coenzyme forms of vitamin B1 (thiamin pyrophosphate) and B6 (pyridoxal-phosphate) form adducts with specific substrates to generate stabilized carbanions as carbon nucleophiles in enzyme reactions. The cyclohexadienyl resonance forms of phenolate anions and carbon 3 of the indole ring as an enamine part structure are also induced to react as carbon nucleophiles.