PMID- 26376956
OWN - NLM
STAT- MEDLINE
DCOM- 20161011
LR  - 20181109
IS  - 1472-8206 (Electronic)
IS  - 0767-3981 (Linking)
VI  - 29
IP  - 6
DP  - 2015 Dec
TI  - Homocysteine excess: delineating the possible mechanism of neurotoxicity and 
      depression.
PG  - 522-8
LID - 10.1111/fcp.12145 [doi]
AB  - Homocysteine (Hcy) is a nonproteogenic sulfur containing amino acid derived from 
      dietary methionine through demethylation. Homocysteine can be re-methylated to 
      methionine [precursor of S-adenosylmethionine (SAM)] via the re-methylation or 
      5-methyltetrahydrofolate pathway or undergoes transsulfuration to form cysteine 
      by the action of metabolic enzymes and cofactors. Impaired metabolism due to 
      genetic alteration in metabolic enzymes (methionine synthase, 
      methyltetrahydrofolate reductase (MTHFR), cystathionine beta-synthase (CbetaS), and 
      cystathionine-gamma-lyase (CgammaL) or deficiency in cofactors (vitamin B6 , B12 , 
      folate) may lead to acquired metabolic anomaly known as hyperhomocysteinemia. Hcy 
      excess decreases the S-adenosylmethionine (SAM)-dependent synthesis of 
      catecholamines, viz. dopamine, norepinephrine, epinephrine, and noncatecholamine, 
      viz. serotonin (5-HT), due to genetic alteration in key enzyme MTHFR in the 
      homocysteine metabolism pathway that leads to depression. Thus, 
      hyperhomocysteinemia (HHcy)-induced SAM level is influenced by the single 
      nucleotide polymorphism (SNP) MTHFR C677T. Furthermore, HHcy leads to production 
      of precarious neurotoxic product homocysteic acid (HCA) and cysteine sulfinic 
      acid (CSA) which acts as an N-methyl-D-aspartate (NMDA) receptor agonist and has 
      neurotoxic effects on dopaminergic neurons. In the current review, an attempt has 
      been made to discuss the neurotoxic effects of HHcy in the pathogenesis of 
      depression.
CI  - (c) 2015 Societe Francaise de Pharmacologie et de Therapeutique.
FAU - Bhatia, Pankaj
AU  - Bhatia P
AD  - CNS Research Laboratory, Pharmacology Division, Department of Pharmaceutical 
      Sciences and Drug Research, Faculty of Medicine, Punjabi university, Patiala, 
      147002, Punjab, India.
FAU - Singh, Nirmal
AU  - Singh N
AD  - Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, 
      Faculty of Medicine, Punjabi university, Patiala, 147002, Punjab, India.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20150917
PL  - England
TA  - Fundam Clin Pharmacol
JT  - Fundamental & clinical pharmacology
JID - 8710411
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 1001-13-4 (homocysteic acid)
RN  - 7LP2MPO46S (S-Adenosylmethionine)
RN  - K848JZ4886 (Cysteine)
RN  - UZY4HYK4ZX (cysteine sulfinic acid)
SB  - IM
MH  - Cysteine/analogs & derivatives/metabolism
MH  - Depression/*etiology/*metabolism
MH  - Homocysteine/analogs & derivatives/*metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/*metabolism
MH  - Neurotoxicity Syndromes/*etiology/*metabolism
MH  - S-Adenosylmethionine/metabolism
OTO - NOTNLM
OT  - depression
OT  - genetic alteration
OT  - homocysteine
OT  - neurotoxicity
OT  - neurotransmitters
EDAT- 2015/09/18 06:00
MHDA- 2016/10/12 06:00
CRDT- 2015/09/18 06:00
PHST- 2015/03/03 00:00 [received]
PHST- 2015/07/06 00:00 [revised]
PHST- 2015/08/18 00:00 [accepted]
PHST- 2015/09/18 06:00 [entrez]
PHST- 2015/09/18 06:00 [pubmed]
PHST- 2016/10/12 06:00 [medline]
AID - 10.1111/fcp.12145 [doi]
PST - ppublish
SO  - Fundam Clin Pharmacol. 2015 Dec;29(6):522-8. doi: 10.1111/fcp.12145. Epub 2015 
      Sep 17.