Delving into the Latest Updates on Glycine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target-

Mechanism

Amino acid modulators

Therapeutic Areas

Other DiseasesEndocrinology and Metabolic DiseaseHemic and Lymphatic Diseases+ [1]

Active Indication

Dietary SupplementDiabetic NephropathiesPsychotic Disorders+ [1]

Inactive Indication

NeuralgiaSchizophrenia

Originator Organization

Hospira, Inc.

Active Organization

Peking University

B. Braun Medical, Inc.Baxter Healthcare Corp.

+ [4]

Inactive Organization

Yale University

Hospira, Inc.

AstraZeneca PLC

+ [1]

Drug Highest PhaseApproved

First Approval Date

US (25 May 1976),

Dietary Supplement

Regulation-

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Structure

Molecular FormulaC2H5NO2

InChIKeyDHMQDGOQFOQNFH-UHFFFAOYSA-N

CAS Registry56-40-6

The involvement of the excitatory amino acids glutamate and aspartate in cerebral ischemia and excitotoxicity is well-documented. Nevertheless, the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied. The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra. Our findings indicated that the reversible loss of field excitatory postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids (L-alanine, glycine, L-glutamine, and L-serine) at their plasma concentrations. These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia, along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors. Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia. It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels, leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation. Thus, previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury. Understanding these pathways could highlight new therapeutic targets to mitigate brain injury.

01 Dec 2024·Poultry Science

Optimal glycine allowance levels in low-protein diets and the dynamic requirement model for broilers

Article

Author: Liu, Yongfa ; Gong, Lu ; Guo, Siyan ; Zhao, Yizhu ; Gao, Xuyang ; Guo, Yuming ; Wang, Bin ; Lv, Zengpeng ; Ma, Jiran

This study aimed to investigate the effects of different glycine levels in low-protein diets on the growth, nitrogen deposition, and expression of intestinal amino acid and glucose transporters in broilers from 29 to 42 d of age, in order to determine the optimal glycine supplementation level. A total of 240 male broilers at 29 days old were randomly assigned to 5 groups: the control group with a crude protein level of 20%, and experimental groups with low-protein diets (LP130) containing 18% crude protein, supplemented with glycine to achieve standardized ileal digestible (SID) glycine + serine to lysine ratios of 134% (LP134), 140% (LP140), and 145% (LP145). The results showed that the LP134 group had similar growth performance and slaughter performance compared to the control group (P > 0.05), whereas other low-protein diet groups had significantly lower growth performance (P < 0.05). Regression analysis determined that the optimal ratio for SID glycine + serine to lysine was 137%. A dynamic model for glycine + serine requirements was established through binary regression analysis: y = 599.051 × BW^{^0.75} + 8.381 × ADG (R² = 0.998, P < 0.001). Feeding LP134, LP140, and LP145 diets significantly improved nitrogen deposition rates in broilers (P < 0.05). Low-protein diets significantly upregulated mRNA levels of b^0,+AT, EAAT3, and SGLT1 genes in the duodenum (P < 0.05). In conclusion, appropriate glycine supplementation in low-protein diets can enhance growth performance, and nitrogen deposition efficiency, and regulate the expression of intestinal amino acid and glucose transporters. The optimal ratio of SID glycine + serine to lysine in low-protein diets for broilers aged 29 to 42 d is 137%.

01 Dec 2024·Clinical Nutrition

Low serum glycine strengthens the association between branched-chain amino acids and impaired insulin sensitivity assessed before and after weight loss in a population with pre-diabetes: The PREVIEW_NZ cohort

Article

Author: Poppitt, Sally D ; Poppitt, Sally D. ; Fogelholm, Mikael ; Silvestre, Marta P ; McLay, Jessica ; Cameron-Smith, David ; Raben, Anne ; Liu, Amy Y ; Silvestre, Marta P. ; Lim, Jia Jiet ; Liu, Amy Y. ; Prodhan, Utpal K ; Prodhan, Utpal K.

AIMAccumulation of circulating branched-chain amino acids (BCAA) is a hallmark feature of impaired insulin sensitivity. As intracellular BCAA catabolism is dependent on glycine availability, we hypothesised that the concurrent measurement of circulating glycine and BCAA may yield a stronger association with markers of insulin sensitivity than either BCAA or glycine alone. This study therefore examined the correlative relationships of BCAA, BCAA and glycine together, plus glycine alone on insulin sensitivity-related markers before and after an 8-week low energy diet (LED) intervention.METHODSThis is a secondary analysis of the PREVIEW (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World) Study New Zealand sub-cohort. Eligible participants with pre-diabetes at baseline who achieved ≥8 % body weight loss following an LED intervention were included, of which 167 paired (Week 0 and Week 8) blood samples were available for amino acid analysis. Glycemic and other data were retrieved from the PREVIEW consortium database. Repeated measures linear mixed models were used to test the association between amino acids and insulin sensitivity-related markers (HOMA2-IR, glucose, insulin, and C-peptide).RESULTSElevated BCAA was associated with impaired insulin sensitivity (p < 0.05), with strength of association (ηp2) almost doubled when glycine was added to the model. However, glycine in isolation was not associated with insulin sensitivity-related markers. The magnitude (β-estimates) of positive association between BCAA and HOMA2-IR, and inverse association between glycine and HOMA2-IR, increased when body weight was higher (Body weight∗BCAA, Body weight∗glycine, p < 0.05, both).CONCLUSIONLow serum glycine strengthened the association between BCAA and impaired insulin sensitivity. Given that glycine is necessary to facilitate intracellular BCAA catabolism, measurement of glycine is necessary to complement BCAA analysis to comprehensively understand the contribution of amino acid metabolism in insulin sensitivity.CLINICAL TRIAL REGISTRATIONThis study was registered with ClinicalTrials.gov (NCT01777893).

100 Deals associated with Glycine

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External Link

KEGG	Wiki	ATC	Drug Bank
D00011	Glycine	B05CX03	DB00145

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Dietary Supplement	-	-	-

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neuralgia	Phase 3	-	AstraZeneca Pharmaceuticals Co. Ltd.	-
Neuralgia	Phase 3	-	AstraZeneca PLC	-
Schizophrenia	Phase 2	-	Yale University	01 Jul 2002
Diabetic Nephropathies	Preclinical	CN	Peking University	15 Sep 2016
Psychotic Disorders	Preclinical	US	Yale School of Medicine	01 Aug 2013
Anemia, Sideroblastic	Preclinical	CA	Dalhousie University	16 Nov 2012
Anemia, Sideroblastic	Preclinical	CA	IWK Health Centre	16 Nov 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EADV2023	Not Applicable	-	-	Herbal extract combination (Dihydroquercetin glucoside, Epigallocatechin gallate glucoside, zinc and glycine)	bexpedyrgu(uncqnzcktz) = No local adverse effects were observed in both groups vsjjgyvvtk (ejmfuznqqs )	Positive	11 Oct 2023
				3% minoxidil solution
FRN 143219 (CIHR), 82100702 (NSFC) (EASD2023)	Not Applicable	Nesidioblastosis	-	Glycine	nleyddcwvw(cyqfyudrim) = hplgtvxnnu kgdamrryxm (slsqhiwzwk ) View more	Positive	05 Oct 2023
				β-alanine	nleyddcwvw(cyqfyudrim) = eloglyswwr kgdamrryxm (slsqhiwzwk ) View more
Pubmed \| J Cachexia Sarcopenia Muscle	Not Applicable	Malnutrition	36	Glycine (BCAA)	fhhypvffik(nbliacmhkj): coeff = -0.27 (95% CI, -0.43 to -0.1), P-Value = 0.002	-	01 Dec 2021
				Glycine
EASD2019	Not Applicable	Diabetes Mellitus	-	Diabetic rats receiving glycine treatment	btozycydwo(vatmozrcqz) = xooodwvgmd keqefmotvt (wzxzpqweab )	-	19 Sep 2019
NCT00338598 (CTgov)	Phase 2	Alcoholism \| Schizophrenia	20	Glycine (Glycine)	vqtrzhzeza(efymvrbasp) = vwswznknnu fsdkkyworo (ogaflihtcu, lgnswbijxn - eotrztecmq) View more	-	12 Apr 2017
				placebo (Placebo)	vqtrzhzeza(efymvrbasp) = ldsoqyehfk fsdkkyworo (ogaflihtcu, suivuxtbda - rhtjnlxxzu) View more
NCT00291226 (CTgov)	Phase 2/3	Schizophrenia	8	Glycine (Glycine)	pcwijrbmwx(dtbjqugrzw) = gzjnsrebzg gtjzbnqnzn (locvmyflcb, cozkjtfequ - rmgimudsjs) View more	-	29 Dec 2016
				Placebo (Placebo Group)	pcwijrbmwx(dtbjqugrzw) = ybgpajwyom gtjzbnqnzn (locvmyflcb, xtpmwvxvkw - dziufupsxv) View more
OP 24 (EASD2016)	Not Applicable	Insulinoma plasma glycine concentrations \| insulin sensitivity \| obesity	-	Glycine	dkydfbizwt(tktmvifaku) = uvduzrbcck esxhewfovv (akrdyqnjif ) View more	Positive	14 Sep 2016
				Glycine	tffzfklyic(bgibuayniz) = kqvoluksxg dmwljjcinv (mbmmajgfvo ) View more
ECCO2013	Not Applicable	-	-	Glycine	avhwfalxbl(ggmijggpiy) = qssgdnmnrb cwykrpsfdb (voppjonynn )	-	01 Feb 2013
				Glycine (Glutamine)	avhwfalxbl(ggmijggpiy) = feoqbjybgp cwykrpsfdb (voppjonynn )
Pubmed \| J Nutr	Not Applicable	-	-	[1,2-13C2]Glycine	cvtvfntrsc(xpxqflrhhk) = utzlaxoits yrnrcubytp (quoxnaktwb ) View more	-	01 Dec 2007