Christoff Odendaal, Dirk-Jan Reijngoud, Barbara M. Bakker
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引用次数: 0
Abstract
The mitochondrial fatty acid β-oxidation (mFAO) is important for producing ATP under conditions of energetic stress, such as fasting and cold exposure. The regulation of this pathway is dependent on the kinetic properties of the enzymes involved. To better understand pathway behaviour, accurate enzyme kinetics is required. Setting up and interpreting such proper assays requires a good understanding of what influences the enzymes' kinetics. Often, knowing the buffer composition, pH, and temperature is considered to be sufficient.
Many mFAO enzymes are membrane-bound, however, and their kinetic properties depend on the composition and curvature of the mitochondrial membranes. These properties are, in turn, affected by metabolite concentrations, but are rarely accounted for in kinetic assays. Especially for carnitine palmitoyltransferase 1 (CPT1), this has been shown to be of great consequence.
Moreover, the enzymes of the mFAO metabolise water-insoluble acyl-CoA derivatives, which become toxic at high concentrations. In vivo, these are carried across the cytosol by intracellular lipid transfer proteins (iLTPs), such as the fatty-acid and acyl-CoA-binding proteins (FABP and ACBP, respectively). In vitro, this is often mimicked by using bovine serum albumin (BSA), which differs from the iLPTs in terms of its binding behaviour and subcellular localisation patterns.
In this review, we argue that the iLTPs and membrane properties cannot be ignored when measuring or interpreting the kinetics of mFAO enzymes. They should be considered fundamental to the activity of mFAO enzymes just as pH, buffer composition, and temperature are.
期刊介绍:
BBA Bioenergetics covers the area of biological membranes involved in energy transfer and conversion. In particular, it focuses on the structures obtained by X-ray crystallography and other approaches, and molecular mechanisms of the components of photosynthesis, mitochondrial and bacterial respiration, oxidative phosphorylation, motility and transport. It spans applications of structural biology, molecular modeling, spectroscopy and biophysics in these systems, through bioenergetic aspects of mitochondrial biology including biomedicine aspects of energy metabolism in mitochondrial disorders, neurodegenerative diseases like Parkinson''s and Alzheimer''s, aging, diabetes and even cancer.