The metabolism and significance of homocysteine in nutrition and health

Abstract

An association between arteriosclerosis and homocysteine (Hcy) was first demonstrated in 1969. Hcy is a sulfur containing amino acid derived from the essential amino acid methionine (Met). Hyperhomocysteinemia (HHcy) was subsequently shown in several age-related pathologies such as osteoporosis, Alzheimer’s disease, Parkinson’s disease, stroke, and cardiovascular disease (CVD). Also, Hcy is associated with (but not limited to) cancer, aortic aneurysm, hypothyroidism and end renal stage disease to mention some. The circulating levels of Hcy can be increased by defects in enzymes of the metabolism of Met, deficiencies of vitamins B6, B12 and folate or by feeding Met enriched diets. Additionally, some of the pharmaceuticals currently in clinical practice such as lipid lowering, and anti-Parkinsonian drugs are known to elevate Hcy levels. Studies on supplementation with folate, vitamins B6 and B12 have shown reduction in Hcy levels but concomitant reduction in certain associated pathologies have not been definitive. The enormous importance of Hcy in health and disease is illustrated by its prevalence in the medical literature (e.g. > 22,000 publications). Although there are compelling data in favor of Hcy as a modifiable risk factor, the debate regarding the significance of Hcy mediated health effects is still ongoing. Despite associations between increased levels of Hcy with several pathologies being well documented, whether it is a causative factor, or an effect remains inconclusive. The present review though not exhaustive, is focused on several important aspects of Hcy metabolism and their relevance to health.

Betaine ameliorates prenatal valproic‐acid‐induced autism‐like behavioral abnormalities in mice by promoting homocysteine metabolism

“…Hcy is a non‐proteinogenic amino acid that forms as an intermediate during the conversion of methionine to cysteine. Previous studies have revealed an association of hyper‐Hcy with several diseases, such as Alzheimer's disease, Parkinson's disease, and stroke . High levels of Hcy are also associated with neuropsychiatric disorders, including autism .…”

“…Hcy is a non‐proteinogenic amino acid that exerts important roles in human physiology. Hyper‐Hcy was shown to be linked with several diseases in the central nervous system, including Alzheimer's disease, Parkinson's disease, and stroke . Abnormally high levels of Hcy have also been observed in serum and urine samples of autistic children and are considered as a potential diagnostic marker for nutritional deficiency that is associated with improper functioning of autistic children .…”

Investigation of serum homocysteine levels in relation to age and sex

“…Hcy is known to be an important biochemical parameter, primarily as a cardiovascular marker, as a determinant of neuronal disorders, renal health, renal failure, diabetes and venous thromboembolism, and even carcinogenesis (Finkelstein et al, 2000;Ravaglia et al, 2005;Wijekoon et al, 2006;Martinez et al, 2017;Ramakrishnan et al, 2006;Kumar et al, 2017). Levels of the advanced biochemical research marker Hcy are a current and reliable tool for the evaluation of the health conditions of humans and animals in different metabolic and endocrinal periods in which the homeostatic continuum of organisms is altered.…”

“…Hcy, which mediates methionine metabolism, is catabolized in the reaction with the vitamin B6 cofactor of Cysteine (Cys). In most tissues, Hcy can be converted back to methionine by this re-methylation reaction, catalyzed by the enzyme "methionine synthase," requiring 5-methylene tetrahydrofolate (THF4) in the form of reduced folate as the methyl donor with vitamin B12 cofactor (Finkelstein et al, 2000;Ravaglia et al, 2005;Wijekoon et al, 2006;Ramakrishnan et al, 2006;Martinez et al, 2017;Mohammad et al, 2010;Kumar et al, 2017;Škovierová et al, 2016).…”

“…Vitamin B12, folate and B6 are essential cofactors in Hcy re-methylation and trans-sulfation pathways. Plasma total Hcy levels are known and accepted to be important biochemical parameters as determinants of possible cardiovascular conditions and consequent mortality in patients with neuronal disorders, renal insufficiency, diabetes, systemic lupus erythematosus and venous thromboembolism, especially coronary-heart disease (Martinez et al, 2017;Ramakrishnan et al, 2006;Kumar et al, 2017). The conclusions of different studies clearly showed that insufficiencies of folate, vitamin B12, or methionin are affecting serum and cellular levels of S-adenosylmethionine (SAM), S-adenosylhomocysteine and homocysteine and are linked with molecular processes leading to oncogenesis and also carcinogenesis (Murin et al, 2017;Martinez et al, 2017).…”