Energy Homeostasis Pathway Suite

Energy homeostasis – the balance between energy uptake and energy expenditure relies on the integration of pathways that produce, convert or store energy and those that detect and respond to environmental cues regarding the energy states and demands of the cell. The tricarboxylic acid cycle, the center of convergence for all metabolic fuels, produces the reducing equivalents whose electrons are passed to oxygen in the electron transport chain (ETC) pathway. The resulting electrochemical gradient that the ETC generates is used to synthesize ATP.  Energy homeostasis is intimately linked to glucose and oxygen homeostasis and the metabolism of lipids and amino acids.  An array of signaling pathways serves as sensors of fuel and energy states and demands or as regulators of appetite-related peptides and their signaling pathways.  Disturbance of energy homeostasis can have serious physiological and pathological consequences. 

To see the pathway suite network for glucose homeostasis click here.

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Citric acid cycle pathway

Insulin signaling pathway

Leptin system pathway

The citric acid cycle pathway, also known as the Krebs or the tricarboxylic acid cycle (TCA), is considered a hub of cellular fuel metabolism. The only precursor of the cycle – acetyl-CoA which can be derived from glucose, fatty acids and amino acid metabolism, is channeled through a cycle of eight reactions that produces reducing equivalents. The electrons are passed to oxygen in the electron transport chain (ETC) while generating an electrochemical gradient that will drive the synthesis of ATP. Click here to explore this essential metabolic pathway.
Insulin signaling plays essential roles in glucose and energy homeostasis. Insulin signaling triggers two important intracellular pathways to fulfill its many roles. Click here to explore this important pathway and those that it activates.

The leptin system acts on two classes of neurons: those expressing the appetite-decreasing peptides POMC and CART and those expressing the appetite-stimulating peptides  NPY and AgRP. A main conduit of the leptin system is the Jak-Stat pathway but other intracellular pathways are also activated. Click here to explore this important signaling system.

Melanocortin system pathway

mTOR signaling pathway

Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway

The melanocortin system relies on several peptides derived from the sequential processing of pro-opiomelanocortin (POMC); collectively, they engage five melanocortin, G protein-coupled receptors. Of these, receptors 3 and 4 are known regulators of energy homeostasis. Receptor 2 is essential for the hypothalamus-pituitary-adrenal (PHA) anti-inflammatory axis with receptor 5 also playing a role in immunity and inflammation; receptor 1 is known for its role in melanogenesis. Click here to explore this complex system.
The mTOR signaling pathway responds to and integrates various environmental cues. Several signaling pathways impinge upon it to stimulate or inhibit its proceedings. Click here to explore this important signaling pathway.
AMPK signaling pathway is a fuel sensor and regulator that promotes ATP-producing and inhibits ATP-consuming pathways. Click here to explore the details of this important signaling pathway.