This post is a spinoff post of red light for depression. Depression can be associated with poor cerebral blood flow. Much of the red light photo biomodulation discussion gets into the improved enzymatic activity of cytochrome C oxidase….which as a heme group. There are two heme containing enzymes that are essential for relaxation of smooth muscle in blood vessels.
Nitric Oxide synthase and guanylate cyclase: two other heme enzymes
Nitric oxide synthase (NOS) plays a role in blood flow by relaxing vascular smooth muscle. The source of NO is the amino acid arginine. There are neuronal and endothelial (blood vessel) isoforms. Wikipedia authors tell us that eNOS several functional groups that include heme, nicotinamide adenine dinucleotide phosphate (NADPH), flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD), and an oxidase domain, which displays binding sites for heme group, zinc, the cofactor tetrahydrobiopterin. Doukov Fig 1. Fig 7 of this publication gives the catalytic cycle of neuronal NOS.
nitric oxide synthase
This image was created using the this NCBI site. The X-ray structures of neuronal nitric oxide synthase (nNOS) with N(omega)-hydroxy-l-arginine (l-NHA) and NO bound Microspectrophotometric techniques confirmed reduced redox state and the status of diatomic ligand complexes during X-ray diffraction data collection. The structure of nNOS-NHA-NO, a close mimic to the dioxygen complex, provides a picture of the potential interactions between the heme-bound diatomic ligand, substrate l-NHA, and the surrounding protein and solvent structure environment. This is one of two sites in the dimeric nNOS molecule. The separate chains are blue and magenta. If there is very local heating around the heme group due to red light absorption, what are the implications for close by groups?
Liu 2024 made a case for neuronal activity regulating blood flow. This is where nNOS comes in! This brings us to the main, blood flow increasing target of nitric oxide: guanylate cyclase:
guanylyl / guanylate cyclase
A previous post addressed light absorption of soluble guanylate cyclase, that is more properly called guanylyl cyclase. sGC is more an absorber of green light that would never get through our skulls or any biological barrier. However, if red and NIR are boosting reactive oxygen species ever so slightly from the mitochondria, we have reactive thiols right next to the catalytic heme group. The sGC post does address use of longish NIR for the purpose of indirectly activating sGC. Here are a few images from that post to illustrates how sGC is an important way of increasing blood flow to our brains when we are stressed and depressed.
Never mind if shear stress or red light causes release of NO from endothelial cells. This is how the blood vessels of our brain relax to increase blood flow. The heme group of soluble guanylate cyclase makes cyclic GMP which activate protein kinase G (PKG). Protein kinase G has many targets that include myosin light chain phosphatase (MYTP) Phosphorylation of the regulatory light chain of myosin is what causes the smooth muscle of our blood vessels to contract.
Soluble guanylate cyclase really does not absorb in the legitimate red and NIR of home therapy devices. If NO is liberated from reactive thiols like Cys78 ….This may be a red light action.
Doukov T, Li H, Soltis M, Poulos TL. Single crystal structural and absorption spectral characterizations of nitric oxide synthase complexed with N(omega)-hydroxy-L-arginine and diatomic ligands. Biochemistry. 2009 Nov 3;48(43):10246-54. PMC free paper The authors measured absorbance of their protein crystals as part of quality control during the process of X-ray detraction used to determine the structure of the pure nNOS protein crystal.
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