Two of the most recent hypotheses concerning metabolism and its regula
tion are examined. First, the theory of distributive regulatory contro
l of metabolic pathways is considered in light of experimental evidenc
e concerning the lack of change in flux of a pathway when individual e
nzymes are either increased or decreased. In addition, it is known tha
t when flux through pathways is either increased or decreased, one fin
ds that the amount of all the enzymes of that path increase or decreas
e simultaneously. Second, the hypothesis of the existence of metabolon
s, complexes of sequential metabolic enzymes, is examined using the Kr
ebs TCA cycle pathway as an example. The evidence from in vitro studie
s with pure enzymes to in vitro metabolic studies with yeast mutants i
s reviewed and evaluated. Unsolved problems concerning these hypothese
s which still exist are considered.