Functions and Signaling Pathways of Amino Acids in Intestinal Inflammation

Table 1

The functions and signaling pathways of EAAs and CEAAs in intestinal inflammation.

Amino acids	Functions	Signaling pathways	References
Tryptophan	↑IL-22, intestinal barrier; ↓Il-1β, Il-6, IL-8, TNF-α, Th1 cells	5-HT, mTOR, AHR; Card9, ACE2, CaSR, MAPK	[11, 13, 58–62]
Phenylalanine	↑anti-inflammatory ability, GSH; ↓TNF-α, IL-6, IL-8, oxidative stress	CaSR	[30, 63, 64]
Methionine	↑intestinal integrity, Cys and GSH; ↓IL-1β, TNF-α, oxidative stress	NF-κB	[65–67]
Lysine	↑GSH, SOD, CAT; ↓IL-1β, IL-6, IL-17, TNF-α, INF-γ	CaSR, NF-κB	[68–71]
Threonine	↑MUC2, IgA, intestinal barrier	NF-κB, mTOR, MAPK	[72–75]
Valine	↑immunoglobulin production; ↓TNF-α, IL-6, INF-γ, IL-1β, and IL-17	GCN2, CaSR	[22, 76]
Leucine	↑intestinal integrity; ↓intestinal inflammation	mTOR, GCN2; NF-κB, MAPK	[22, 77, 78]
Isoleucine	↑expressions of β-defensins	GCN2, GPCRs, MAPK	[22, 79]
Arginine	↑regulation of intestinal microbiota; ↓oxidative stress, IL-1β and IL-6; ↓inflammatory neutrophil recruitment	NF-κB; iNOS; MAPK	[31, 80–84]
Histidine	↓IL-6, IL-8, TNF-α	NF-κB	[3, 85, 86]

Functions of EAAs and CEAAs in intestinal inflammation mainly depend on NF-κB, iNOS, MAPK, ACE2, GCN2, CaSR, and mTOR signaling pathways. AHR: aryl hydrocarbon receptor; 5-HT: 5-hydroxytryptophan; Card 9: caspase recruitment domain family member 9; mTOR: mechanistic target of rapamycin; MUC2: mucin 2; MPO: myeloperoxidase; CaSR: calcium-sensing receptor; MAPK: mitogen-activated protein kinase; NF-κB: nuclear factor-kappa-B; ROS: reactive oxygen species; Cys: cysteine; GSH: glutathione; iNOS: inducible nitric oxide synthase; ACE2: angiotensin-converting enzyme 2; GPCRs: G protein-coupled receptors; SOD: superoxide dismutase; CAT: catalase; GCN2: general controlled nonrepressed kinase 2.