Biochemical Basis of Circadian Rhythms

Introduction

Circadian rhythms are biological processes that follow a 24-hour cycle and are found in almost all living organisms, from bacteria to humans. These rhythms regulate various physiological functions such as sleep-wake cycles, hormone production, metabolism, and body temperature. The biochemical basis of circadian rhythms involves complex molecular mechanisms that are controlled by a network of genes and proteins.

Molecular Clock

At the core of the circadian clock is a transcription-translation feedback loop involving a set of clock genes. The central clock genes include Period (Per), Cryptochrome (Cry), Clock, and BMAL1. These genes interact with each other to form a regulatory loop that drives the oscillation of gene expression over a 24-hour period. The production and degradation of these proteins create a self-sustaining rhythm that regulates various cellular processes.

Post-Translational Modifications

In addition to transcriptional regulation, post-translational modifications play a crucial role in the regulation of circadian rhythms. Phosphorylation, acetylation, and ubiquitination of clock proteins can modulate their stability, activity, and subcellular localization. For example, the phosphorylation of PER proteins targets them for degradation, while acetylation of BMAL1 regulates its transcriptional activity. These modifications fine-tune the molecular clock and ensure its proper functioning.

Integration of External Cues

While the core circadian clock operates autonomously, it can be influenced by external cues such as light, temperature, and feeding schedules. The suprachiasmatic nucleus (SCN) in the brain receives light input from the retina and synchronizes the internal clock with the external environment. Light signals are transmitted to the SCN via the retinohypothalamic tract, leading to the suppression of melatonin production and the adjustment of the sleep-wake cycle. Temperature cycles and feeding rhythms also contribute to the entrainment of circadian rhythms by influencing gene expression and protein activity.