This chapter discusses the control of metabolism by dynamic macromolecular interactions. Metabolic pathways are controlled and directed by pacemaker, bottleneck, and key enzymes. In general, no single enzyme is responsible for the control of a whole metabolic pathway. In pursuing the pacemaker theory, attempts are made to quantify metabolic regulation, and one studies each enzyme in a sequence separately in situ, determines its kinetic properties in the greatest possible detail and accuracy, and then seeks to determine how it works when it is in the intact cell. In prokaryotes and in eukaryotes the largest macrocompartment is the cytoplasm, containing quantities of soluble enzymes and is full of membranes associated with a great variety of organelles. A theoretical analysis of glycolysis in human erythrocytes has been provided, implicitly assuming that it proceeds in a homogeneous bulk solution without any interaction among the participating enzymes.