Circadian Rhythms of Liver Enzyme Activity

This is so basic that I even teach it in Intro Bio:

Wherever the master clock may be located (SCN, pineal or retina) in any particular species, its main function is to coordinate the timing of peripheral circadian clocks which are found in every single cell in the body. Genes that code for proteins that are important for the function of a particular tissue (e.g., liver enzymes in liver cells, neurotransmitters in nerve cells, etc.) show a daily rhythm in gene expression. As a result, all biochemical, physiological and behavioral functions exhibit daily (circadian) rhythms, e.g., body temperature, blood pressure, sleep, cognitive abilities, etc.

And here is a little bit more detail:

What does a peripheral clock in a cell do? It acts as a relay – turning on and off batteries of genes in a tissue-specific way. So, for instance, in a liver cell, there will be three categories of genes:
First, genes that liver does not use (needed for muscle contraction or gas exchange, for instance, in other organs) are not expressed at all.
Second, genes involved in general cell metabolism (e.g., genes that code for proteins that are involved in transcription, translation or DNA repair) are expressed at high levels constituitively – there is no variation in levels over time.
Finally, there are genes that are expressed with a circadian pattern. Expression of these genes is under the control of the circadian clock in the liver cell. Which genes are those? Those that code for proteins which serve a liver-specific function, e.g., various enzymes used in biosynthesis, detoxification etc.
Are all those genes expressed at the same time? No! They are expressed in several “batteries” – some in the morning, some in the afternoon, some at night, etc. Thus, for instance, alcohol dehydrogenase (together with hundreds of other genes) is expressed in the late evening and early night – allowing one to drink more alcohol than in the morning. Importantly – most of the genes are not switched completely on and off – they are just expressed a little more or a little less over the 24-hour period.
What this all implies is that there is no down-time for the liver. It always does something, only that “something” changes over time. The same goes for every other cell-type in the body.

But now, Michael Hastings et al. have gone a step further. They have shown not just that key tissue-specific genes cycle, but also that the gene products – the proteins – also cycle:

The new research used state of the art proteomic analysis to examine clock-controlled changes in the livers of normal mice and mice with genetically impaired body clocks.
Dr Hastings went on: “We discovered that around one fifth of liver enzymes show circadian rhythms, which means that the metabolic capabilities of the liver changes dramatically between day and night as different groups of proteins and enzymes are turned on and off in sequence. This is brought about by a new level of chemical co-ordination that we were never aware of, involving sophisticated modifications of proteins and their time-dependent synthesis.

Nice to see the story getting more complete. Rhythmicity of gene expression is in itself not sufficient. Sometimes there are cycles in transcription but not translation, sometimes the other way round. It’s nice to know that both processes show circadian rhythms in at least one studied tissue, the liver.


Comments are closed.