02Aug/16

The Cholesterol Paradox, Part I

Here is the quote from the above diagram from Metabolic Regulation: A Human Perspective by Keith N. Frayn, regarding cholesterol regulation (emphasis added): “The full length SREBP protein is located in the ER. It is associated with the SREBP cleavage activating protein (SCAP), which “senses” the level of cholesterol, or related sterols, within the membrane of the ER. When the cholesterol content is low, the SCAP-SREBP complex migrates to the Golgi complex, where specific proteases cleave SREBP to release the N-terminal portion, “mature” SREBP. Mature SREBP moves to the nucleus where it binds to sterol response elements in the promoter regions of many genes.… Read More...
01Aug/16

Regulation of Mitochondrial Metabolism and PH

The following is an excellent excerpt from Metabolic Regulation: A Human Perspective, by Keith N. Frayn. After reading it, the connection between metabolism (specifically mitochondrial oxidative metabolism capacity) and PH should be clear. I’ll leave the in depth commentary of why (including how, if this is true, PH is restricted to affecting lungs as opposed to systemic circulation) for another post: “An important aspect of metabolic regulation and its adaptation to different circumstances is the use of oxygen to oxidize nutrients and, hence, generate ATP. There are two aspects relevant to this chapter. The first is a series of mechanisms that increase the ability of tissues to conduct oxidative metabolism.… Read More...
31Jul/16

The Pentose Phosphate Path and PH, Part I – RBCs, G6PD, & GSH

The pentose phosphate pathway (PPP) is a metabolic pathway that parallels glycolysis. In cells, within the cytosol, glucose is converted into glucose 6-phosphate (catalyzed by the enzyme hexokinase), which can then either 1) enter glycolysis (and subsequent glucose oxidation via citric acid cycle) to produce ATP, or 2) enter the PPP. The PPP (diagram below) is primarily an anabolic pathway; the primary purpose being the following: to produce molecules (specifically 5 carbon sugars, and Ribose-5-phosphate) used for fatty acid synthesis, nucleic acid synthesis, and protein synthesis. However, another important purpose of the PPP is to produce NADPH, a high energy electron carrier.… Read More...
31Jul/16

Thought Of The Day – AMPK, Pulmonary Vasculature & RV

Today’s thought stems from a quote I found reading Metabolic Regulation: A Human Perspective by Keith N. Frayn. This is one of my new favorite books… Quote: “AMPK senses energy status of the cell: when there is a drain on ATP, AMP rises and the AMPK is activated, leading in turn to inhibition of ATP utilizing pathways (particularly biosynthetic pathways) and activation of ATP-generating pathways (glucose uptake, glycolysis, fatty acid oxidation).” Thought: AMPK (5′ AMP-activated protein kinase) activation in some form, either via dietary means, or as a drug target, would seem to be a good idea for the pulmonary vasculature as it would potentially prevent proliferation of PASMC’s and PAEC’s, and perhaps even adventitial fibroblasts (because of the “preventing biosynthetic pathway” feature stated above).… Read More...