(from the Greek ἀνά
= 'up' and πληρόω
= 'to fill') are chemical reaction
s that form intermediates of a metabolic pathway
. Examples of such are found in the citric acid cycle
(TCA cycle). In normal function of this cycle for respiration, concentrations of TCA intermediates remain constant; however, many biosynthetic reactions also use these molecules as a substrate. Anaplerosis is the act of replenishing TCA cycle intermediates
that have been extracted for biosynthesis (in what are called cataplerotic reactions
The TCA cycle is a hub of metabolism, with central importance in both energy production and biosynthesis. Therefore, it is crucial for the cell to regulate concentrations of TCA cycle metabolites in the mitochondria. Anaplerotic flux must balance cataplerotic flux in order to retain homeostasis of cellular metabolism.
Reactions of anaplerotic metabolism
There are 4 major reactions classed as anaplerotic, and it is estimated that the production of oxaloacetate from pyruvate has the most physiologic importance.
is created by PEP carboxylase
and malate dehydrogenase
in the cytosol
. Malate, in the mitochondrial matrix
, can be used to make pyruvate
(catalyzed by malic enzyme
) or oxaloacetic acid
, both of which can enter the citric acid cycle
can also be used to produce oxaloacetate during anaplerotic reactions in various cell types through "glutaminolysis", which is also seen in many c-Myc transformed cells.DeBerardinis, et al. The biology of cancer:metabolic reprogramming fuels cell growth and proliferation. Cell Metabolism 7, January 2008
Diseases of anaplerotic metabolism
Pyruvate carboxylase deficiency is an inherited metabolic disorder where anaplerosis is greatly reduced. Other anaplerotic substrates such as the odd-carbon-containing triglyceride triheptanoin
can be used to treat this disorder.