Revista Adolescência e Saúde

Revista Oficial do Núcleo de Estudos da Saúde do Adolescente / UERJ

NESA Publicação oficial
ISSN: 2177-5281 (Online)

Vol. 15 nº 4 - Oct/Dec - 2018

Review Article Imprimir 

Páginas 104 a 113


Homocystein and cysteine: markers of cardiovascular risk in adolescents

Homocisteína y cisteína: marcadores de riesgo cardiovascular en adolescentes

Homocisteína e cisteína: marcadores de risco cardiovascular em adolescentes

Autores: Luana de Oliveira Leite1; Priscila Ribas de Farias Costa2; Maria Ester Pereira da Conceição-Machado3; Jacqueline Costa Dias Pitangueira4

1. Master in the Post-graduation program in Foods, Nutrition and Health (PPGANS), School of Nutrition, Federal University of Bahia (UFBA). Teacher of the Nutrición course, Department of Life Sciences, State University of Bahia (UNEB). Salvador, BA, Brazil
2. Doctorate in Collective Health, Institute of Colective Health, Federal University of Bahia (UFBA). Teacher of the Post-graduation program in Foods, Nutrition and Health (PPGANS), School of Nutrition, Federal University of Bahia (UFBA). Salvador, BA, Brazil
3. Doctorate in Medicine and Health, Faculty of Medicine, Federal University of Bahia (UFBA). Teacher of the Post-graduation program in Foods, Nutrition and Health (PPGANS), School of Nutrition, Federal University of Bahia (UFBA). Salvador, BA, Brazil
4. Doctorate in Medicine and Health, Faculty of Medicine, Federal University of Bahia (UFBA). Teacher of the Nutrition course, Center of Health Scieces, Federal University of the Reconcavo Baiano (UFRB). Salvador, BA, Brasil

Luana de Oliveira Leite
Escola de Nutrição da Universidade Federal da Bahia (UFBA)
Rua Basílio da Gama, s/nº, Canela
Salvador, BA, Brasil. CEP: 40110-040
(luanaleite_nutri@yahoo.com.br)

PDF Portuguese      


Scielo

Medline


How to cite this article

Keywords: Homocysteine, cysteine, adolescent.
Palabra Clave: Homocisteína, cisteína, adolescente.
Descritores: Homocisteína, cisteína, adolescente.

Abstract:
OBJECTIVE: Describe the association between hyperhomocysteinemia and hypercisteinemia and cardiovascular risk factors in adolescents.
DATA SOURCES: The literature review was conducted from January to April of 2018 in the following electronic databases: Latin American and Caribbean Literature in Health Sciences (LILACS), Scientific Electronic Library Online (SciELO), Medical Literature Analysis and Retrieval System Online (Medline) via PubMed and in bibliographical references of the selected articles, combining the terms homocysteine, cysteine, cardiovascular risk and adolescents in Portuguese and English. Original and review articles were selected, including systematic reviews and meta-analyzes, without time and language restrictions.
DATA SYNTHESIS: The review was divided into five topics: 1) Introduction, with a brief focus on the problematization of hyperhomocysteinemia and hypercysteinemia in adolescence as a cardiovascular risk factor; 2) Homocysteine: history, concept and metabolism; 3) Hyperhomocysteinemia in adolescentes: classification, prevalence, causes and other cardiovascular risk factors; 4) Cysteine: history, concept and metabolism; 5) Hypercysteinemia in adolescents: classification, prevalence, causes and other cardiovascular risk factors.
CONCLUSION: Hyperhomocysteinemia and hypercysteinemia are associated with body adiposity, increased blood pressure, altered serum lipid levels and insulin resistance in adolescents. Therefore, considering that the atherosclerotic process begins long before clinical aspects are detected, further studies are needed that identify the role of homocysteine and cysteine in the development of traditional cardiovascular risk factors among adolescents.

Resumen:
OBJETIVO: Describir la asociación entre hiperhomocisteinemia y hipercisteinemia y factores de riesgo cardiovascular en adolescentes.
FUENTE DE DATOS: Una revisión de la literatura se llevó a cabo en los meses de enero a abril de 2018, las bases de datos: Literatura Latino Americana y el Caribe de Ciencias de la Salud (LILACS), Scientific Electronic Library Online (SciELO), Medical Literature Analysis and Retrieval System Online (Medline) vía de PubMed y listas de referencias de artículos seleccionados, que coinciden con los términos 'homocisteína', 'cisteína', 'riesgo cardiovascular' y 'adolescentes', en los idiomas portugués e Inglés. Se consideraron artículos originales, de revisión, incluyendo revisiones sistemáticas y meta-análisis, sin restricción de tiempo e idioma.
RESUMEN DE LOS RESULTADOS: El examen se divide en cinco temas principales: 1) Introducción, con un breve enfoque en el cuestionamiento de la hiperhomocisteinemia y hipercisteinemia en la adolescencia como un factor de riesgo cardiovascular; 2) La homocisteína: la historia, el concepto y el metabolismo; 3) La hiperhomocisteinemia en adolescentes: clasificación, prevalencia, causas y otros factores de riesgo cardiovascular; 4) Cisteína: historia, concepto y el metabolismo; 5) Hipercisteinemia en adolescentes: clasificación, prevalencia, causas y otros factores de riesgo cardiovascular.
CONCLUSIÓN: La hiperhomocisteinemia y hipercisteinemina están asociados con la adiposidad, al aumento de la presión arterial, la alteración de los niveles de lípidos séricos, y resistencia a la insulina en adolescentes. Teniendo en cuenta, por lo tanto, que el proceso aterosclerótico comienza mucho antes de ser detectados clínicamente, se torna necesario más estudios para identificar el papel de la homocisteína y cisteína en el desarrollo de factores de riesgo cardiovascular en adolescentes.

Resumo:
OBJETIVO: Descrever a associação entre hiper-homocisteinemia e hipercisteinemia e fatores de risco cardiovascular em adolescentes.
FONTES DE DADOS: A revisão da literatura foi realizada nos meses de janeiro a abril de 2018 nas bases de dados: Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), Scientific Electronic Library Online (SciELO), Medical Literature Analysis and Retrieval System Online (Medline) via PubMed e em referências bibliográficas dos artigos selecionados, combinando-se os termos 'homocisteína', 'cisteína', 'risco cardiovascular' e 'adolescentes', nos idiomas português e inglês. Foram considerados artigos originais, de revisão, incluindo revisões sistemáticas e meta-análises, sem restrição de tempo e idioma.
SÍNTESE DOS DADOS: A revisão foi dividida em cinco tópicos principais: 1) Introdução, com breve enfoque na problematização da hiper-homocisteinemia e hipercisteinemia na adolescência enquanto fator de risco cardiovascular; 2) Homocisteína: histórico, conceito e metabolismo; 3) Hiper-homocisteinemia em adolescentes: classificação, prevalência, causas e outros fatores de risco cardiovascular; 4) Cisteína: histórico, conceito e metabolismo; 5) Hipercisteinemia em adolescentes: classificação, prevalência, causas e outros fatores de risco cardiovascular.
CONCLUSÃO: A hiper-homocisteinemia e hipercisteinemina estão associadas à adiposidade corporal, aumento da pressão arterial, alteração dos níveis de lipídios séricos, além de resistência à insulina em adolescentes. Considerando-se, portanto, que o processo aterosclerótico tem início muito antes de aspectos clínicos serem detectados, ainda se faz necessário mais estudos que identifiquem o papel da homocisteína e cisteína no desenvolvimento de fatores de risco cardiovascular tradicionais entre adolescentes.

INTRODUCTION

According to O World Health organization, cardiovascular diseases (CVD) are the leading cause of death worldwide1. In Brazil, they are responsible for the death of 350,000 people/year, which corresponds to 30% of deaths in the country2 the risk factors classic, how hypercholesterolemia, high blood pressure (hypertension), Mellitus diabetes (DM), smoking, obesity, physical inactivity and family history is are responsible for two - thirds of the causes of deaths from cardiovascular disease1.

Although the clinical manifestations of CVD are usually observed in the adult phase, there is strong evidence that these diseases can begin in childhood and adolescence.3.4 Autopsies and evaluation of images have revealed the presence of fatty streaks and fibrous plaques in the arteries of adolescents who are exposed to classic cardiovascular risk factors4 .

It is important to note that 25% of individuals with chronic diseases do not Transmissible, including CVD, do not fall within the range of traditional risk factors, so it is difficult to prevent5. Thus, other risk factors have been evaluate and the studies suggest homocysteine (Hcy) and cysteine (Cys) as markers no classics for cardiovascular diseases, whose elevated plasma levels may contribute to the early identification of cardiovascular risk6-7.

The Hcy is a sulfur amino acid synthesized exclusively as an intermediate product of the intracellular metabolism of the essential amino acid methionine. The interest in Hcy as causal risk factor for CVD in childhood and adolescence was whetted by the observation that over 50% of children with genetic disorder of homocysteinuria died by premature vascular disease, as well as the fact that high levels of Hcy they are associated with factorsphysiological and nutritional factors6.7. Referring to Cys, although it is structurally similar and metabolically related to the Hcy, its association with the DCNT has received less attention8. Some studies, however, have identified a significant relationship between high concentrations of Cys and CVD8, 7.

Although the evidence suggests that hyperhomocysteinemia and hypercysteinemia are risk factors for cardiovascular diseases in adults, there is little conclusive information on the levels of these amino acids in adolescence. There is no consensus for the association between high levels of Hcy and Cys, body composition and metabolic risk factors for obesity and cardiovascular diseases in this stage. Therefore, this review was addressed to describe the association between high levels of homocysteine and cysteine and cardiovascular risk in adolescents.


DATA SOURCE

The search of articles was carried out in the months of January to April 2018, in the databases: Latin American and Caribbean Literature of Health Sciences (LILACS), Scientific Electronic Library Online (SciELO) andMedical Literature Analysis and Retrieval System Online (Medline) via PubMed and reference lists of selected articles that match the terms 'homocysteine', 'cysteine', 'cardiovascular risk' and 'adolescents', in Portuguese and English. Original articles were considered for review, including systematic reviews and meta-analysis, without restriction of time and language.


HOMOCYSTEIN

HISTORICAL, CONCEPT AND METABOLISM

The Hcy It was discovered in 1952, but in 1969 McCully et al.9 identifies the clinical importance of homocystinuria, suggesting for the first time the link between the genetic metabolic disorder caused by the deficiencyhomozygous of cystathionine β-sintasa and appearance of atherosclerosis9.

Hcy is a sulfur compound that contains a thiol (-SH) grouping, which allows passing by a series of biochemical reactions common to amino acids that contain a sulfur atom9,10. It is a non-essential amino acid that is not present in the human diet or in the body's proteins because there are no specific codons for its transcription. Therefore, it is a by-product of the metabolism of methionine, formed exclusively from the demethylation of the methionine in the diet or its catabolism10,11. The methionine beautifully set at mainly in the liver is catabolized to Cys route of transulphurization, generates Hcy as intermediary in that process11.

The Hcy does not accumulate in cells (minimum concentrations of 1 to 5 μ mol/L) and the fraction which is not metabolized, the Cys or methionine , enters the circulation. Approximately 70 to 80% of Hcy in the blood it binds to plasma proteins, especially albumin, forming disulfide bridges. Of the rest, a fraction (2 to 5%) remains in the free (reduced) form and the others spontaneously condense through oxidation through the formation of a disulfide bridge, which can include homocysteine (homocysteine dimer) and disulfides mixed such as homocysteine-cysteine. Thus, homocysteine total plasma is the sum of all the free-form and bound to proteins that contain athiol grouping10 , 11.

Figure 1 represents methyl cyclo (transmethylation, transulphurization and rememetilation). A part of the methionine in the body is used in the formation of proteins. The other is activated by adenosine triphosphate (ATP) to form S-adenosylmethionine (AdoMet). In the methylation reaction, called transmethylation, S-adenosil is formed homocysteine which is hydrolyzed, regenerating Hcy that becomes available to start a new cycle of methyl group transfer (remethylation) or is metabolized to form Cys (transulphurization )11. Therefore, through transmethylation allows the recovery of methionine so that Hcy pair contributes to its maintein simultaneously (Hcy and methionine they are precursors to each other).


Figure 1. The metabolic pathways of homocysteine ​​(methyl cycle).
Legend: Enzymes involved in homocysteine ​​metabolic pathways: 1) Methionine adenosyltransferase; 2) several Methyltrasferases; 3) adenosyl-homocysteinehydrolase; 4) methionine synthase; 5) betaine Methyltrasnferase-homocysteine; 6) N5 , 10 -Methylenetetrahydrofolate reductase; 7) b cystathionine synthase; 8) cystathionase. ATP: adenosine triphosphate; THF: tetrahydrofolate; 5.10-MTHF: 5,10-methylenetetrahydrofolate; N5MHTF: N-5-methyltetrahydrofolate; B6: pyridoxine; B9: Folate; B12: cyanocobalamin.
* Source: Figure schematized by the authors based on the references.10,11,21,24,29,31



On track of transulphurization, that occurs when there is methionine overload, there is condensation of Hcy with serine to form cystathionine by an irreversible reaction, which is catalyzed by the enzyme cystathionine- β-sintasa using pyridoxal 5'-phosphate as co-factor, generated from pyridoxine (vitamin B6). The cystathionine is hidrolizad to a second enzyme is also dependent on the vitamin B6, γ-cystathionase NDO form Cys and α-ketobutyrate. The cycle of transulphurization It is available in the liver, kidney, pancreas and the intestines and is the main responsible for the catabolism of Hcy (degrading approximately 50% circulating Hcy)10,11.

Under conditions in which a negative balance of methionine occurs, preferably when there is no fasting, it occurs through resection: Hcy receives a methyl group N-5-methyltetrahydrofolate (N5MTHF), the main form of folate plasma, or betaine, to regenerate methionine. The reaction with N5MTHF is catalyzed by methionine synthases (MS) and occurs in all tissues, also know way as cycle folate, thus it requires an adequate supply of folic acid, as cyanocobalamin (vitamin B12), as it depends methyl- co-factor cobalamin cyanocobalamin11.


HYPERHOMOCYSTEINEMIA IN ADOLESCENTS

CLASSIFICATION, PREVALENCE AND CAUSES

For teens there´s no values establishe for hyperhomocysteinemia. In a review of Refsum et al. 12 they proposed limits of hyperhomocysteinemia of 8µmol/L in areas with folic acid supplements and 10μmol/L in áreas without folic acid supplementation for children and adolescents under 15 years, and even Additional property ieron a breakpoint ≥ of 15µmol/L for adolescents with 15 or more years of age. Studies have adopted this cut-off point or reference values for adults, or even the 90th percentile of the sample it self13-14. The result is the prevalence of hyperhomocysteinemia among adolescents in Brazil, ranging from 9.9%13 to 24%15, and in the global context, from 10.1%16 to 44.6%14.

Studies have shown that in childhood and adolescence the average values of homocysteine they are half of the values found in the adult population. Among 774 teenagers Kuwaiti, the average found by Akanji et al.17 it was 6.57 µmol/L. In a study conducted in Greece with 524 children and adolescents, it was obseved an average of Hcy of 7.8 μmol/L for men and 5 μmol/L for women of 718. In Chile, a study carried out with 80 children and adolescents from 6 to 15 years of age and without a family history of cardiovascular disease, they found an average of 5.8 μmol/L (no family history) and 7.2 μmol/L ( with family history is )19 . Another study from 1992 to 1994 and 1137 children and adolescents (53% white, 47% blacks) from 5 to 17 years examined in Bogalusa Heart Study, it has an average of 6.1 μmol/L20.

In adolescence, high levels of Hcy They can arise due to genetic alterations s, endocrines, sickle cell disease or nutritional factors 14. Once formed, the Hcy it is released into the plasma of the tissues in small amounts. Inclusive, when there is an excess of methionine, the surplus Hcy is redirected to the route of transulfurization. All these mechanisms, in some way, controls their plasma concentration10,11.

When it stops the balance of synthesis and turnover of Hcy, the Hcy and derivatives accumulate in the cells and can then overcome the cell membrane and accumulate in the plasma. Therefore, changes in any step in the metabolism of methionine and low ingest ion of folate and vitamin B6 and 12 which act as cofactors Enzymes involved in the cycle, can lead to Hcy elevated in the blood. Values plasma and urine Hcy reflect cellular synthesis, utilization and integrity of their pathways of metabolism10,11.

Among the factors that contribute most to the increase in Hcy there are the genetic alterations that involve the enzymes involved in the metabolism of Hcy: mutations in the enzyme gene cystathionine β-sintasa (present on the way of transulfurization); the shape thermo-labile enzyme MTHFR the resulting transition 677 Cytosine → Timina in your gene (present in the pathway of transulphurization) and mutations in the gene for MS (which catalyzes remetilation Hcy pair to methionine)21.

Table 1 summarizes the main cause's descrit Sy other factors that can lead to high circulating levels Hcy not only in adolescents, but in the population in general. dditional property ieron a breakpoin


HIPERHOMOCYSTEINEMIA AND CARDIOVASCULAR RISK IN ADOLESCENTS

The relationship between hyperhomocysteinemia and cardiovascular risk factors becomes increasingly well- founded, although in the early stages of life the evidence is still rare. The prevention of atherosclerotic disease should begin in childhood and adolescence3,4 with periodic evaluation not only of the lipid profile, but of other risk factors. Therefore, studies have focused on evaluating the association between non- traditional risk factors, such as hyperhomocysteinemia, and traditional risk factors for VCD in adolescents13,15,18,22,23.

At the end of the 90s, Oshaug et al.24 they showed that concentration of homocysteine Plasma in children was linked to obesity and correlated with fat intake. These authors suggested that moderate fat restriction decreases plasma concentrations of Hcy. In the same period, another study with children and adolescents found, inclusive in the pediatric population, high levels of Hcy associates with high levels of systolic blood pressure and weight gain25.

Some studies about school age and adolescents show direct correlation of levels of homocysteine of folic acid, vitamin B12 and overweight as measured by body mass index (BMI )18,22,26,27,23. A national study described by Brasileiro et al.23 made with teenagers obes and eutrophic , found that the levels of homocysteine, folic acid and vitamin B12 did not show statistically significant differences in terms of anthropometric measurements. However, a study in China Met or significantly higher levels in obese children compared with those who are overweight22. The analyzes performed by Papandreou et al.18,26,27 in Greece they found that the levels of homocysteine They correlate well, both with excess weight and high blood pressure.

More recently, the use of data information from baseline of a Brazilian cohort study conducted with children and adolescents, Costa et al.28 identified that the increase in the levels of Hcy (> 8,6 µmol/L) was associated aronoverweight (PR=2.52; p=0.03) increased and blood pressure (RP=1.28; p=0.03). The same authors that evaluated the longitudinal data found that regardless of age, sex, socioeconomic status, diet intake and physical activity, children and adolescents of the quintile or quantile of distribution of the levels of homocysteine (> 8,6 µmol/L) showed an increase of 0.50 (p<0.01) in the mean increase in the Z score of the BMI and an increase of 3.62cm (p <0.01) in the mean waist circumference (CC) after a year of accompaniment29.

In another study conducted in Brazil, the Hcy average was higher in children or adolescents diagnosed with obesity (9.2 μmol/L) and also in those with insulin resistance (IR) (10.0 μmol/L), only this being the last statistically significant result (p=0.011)15. The research carried out in São Paulo identified for the first time the association between increased waist circumference and high levels of Hcy and Cys in children and adolescents from 6 to 11 years, regardless of their nutritional status. It was found that children with increased waist circumference, including eutrophic, they were 2.34 times more likely to have high levels of homocysteine (above the 90th percentile, that is, >7.3 μmol/L)13.

The results derived from experiments in vivo and in vitro showed that the association of Hcy with excess body weight may be linked to adipose tissue dysfunction by inhibiting lipolysis by means of protein activationkinase AMP - activated (which is an important sensor of cellular energy level), acting as anti-lipolysis in adipocytes, favoring the accumulation of fat30. The link between the increase in levels of homocysteine and obesity also seems to be related to IR in young populations. Some studies in children and adolescents indicate that weight gain is associated with high concentrations of homocysteine and hyperinsulinemia15,24,31. However, no correlation was found between hyperhomocysteinemia and IR in the study of Brasileiro et al.23.

Other studies have related hyperhomocysteinemia to changes in the metabolism of HDL cholesterol (HDL- c). And it suggests that individuals with hyperhomocysteinemia they have HDL-C dysfunctional, as it became known that the levels of homocysteine s plasma high diminishes the expression of the apolipoprotein AI, one of the main apolipoprotein constituents of that cholesterol17. Therefore, some studies have identified this association15,16,14,28,32.

In the Costa et al.28 it was observed an association between high levels of Hcy (>8.6 μmol/L) and low levels of HDL-C (OR=1.21, p=0.03) and hypertriglyceridemia (PR=1.62, p=0.03) in children and adolescents. Data accompanying identified that after one year, regardless of age, sex, socioeconomic status, diet or anthropometric status, when the levels Serum Hyc were above the fifth quintile distribution (>8.6 mmol/L), HDL-c decreases average 2,91mg/dl (p<0.01), whereas triglyceride levels increased on average 1,58mg/dl (p<0.01)32. In the study of Leal et al.15, the average of Hcy was higher in children and adolescents with low HDL-c (9.3 μmol/L) than in those with HDL- c adequate, although not statistically significant.


CISTEINE

HISTORICAL, CONCEPT AND METABOLISM

In mammals, the Cys it is synthesized from two other amino acids: methionine provides sulfur atom, and serine enters the main carbon chain (Figure 1). In a series of reactions, the -OH group of the serine is substituted orby a group -SH derived from methionine to form the Cys. This amino acid belongs to the group of sulfhydryl s and has structural and chemical properties similar to those of Hcy and, also, the oxidation of Cys is involved in the processes of thrombogenesis and atherogenesis10.


HYPERCISTEINEMIA In ADOLESCENTS

CLASSIFICATION, PREVALENCE AND CAUSES

In adults, the plasma concentration of cysteine is about 20 times higher than the level of Hcy (<250 μmol/L)33. In adolescents, average values Cys they vary according to the studies. Costa et al.28 found an average of 406.8 μmol/L for women and 410.4 μmol/L for men. Silva et al.13 identifies a general average of Cys of 366.4 µmol/L. While the study from Elshorbagy et al.3, 4 detected 204 average μmol/L (male) and 201 μmol/L (female).

Although no limit to hipercisteinemia in children and adolescents is not established, the study in São Paulo uses Cys values above the 90th percentile of the sample itself (445.0 umol/L) as cohort point to classify levels Plasmatic high Cys, identifying a hypercysteinemia prevalence of 9.6% (male) and 9.0% (female)13.


HYPERCISTEINEMIA AND CARDIOVASCULAR RISK IN ADOLESCENTS

As well as hyperhomocysteinemia, high values of Cys they are also related to DCNT, especially obesity and cardiovascular diseases. However, its possible adverse effects on cardiovascular disease have received little attention so far8,7,33 and there is a paucity of studies on the relationship between the cysteine and cardiovascular risk in adolescents13,28,29,34.

The first studies were about the relationship between Cys and the BMI body weight classified as strong predictor of high values of Cys. Recent studies record the role of obesity generator Cys, which also seems to extend tothe age group of children and youth 34 , 35 . In children and adolescents in São Paulo they found that individuals with high waist circumference, including eutrophic, were twice as likely to have high Cys (above the 90th percentile) 13 . Already in a survey of 984 Hispanic children and adolescents, between 4 and 19 years of age , d the study Live The Family, the top quartile of Cys independently associated with a five times higher risk of obesity and twice the RI risk (adjusted for% body fat ) 3 4 .

In the study by Costa et al.28 the prevalence of hpercysteinemia (> 463.4 μmol/L ) was 2.52 times greater (p=0.03) in overweight children of school age compared to normal individuals. In addition, the increase in the levels of the total Cys (> 463.4 μmol/L ) were significantly associated with the increase in blood pressure (PR=1.28, p=0.03). After 1 year of accompaniment , the same authors showed that, regardless of age, gender, socioeconomic level, food intake and physical activity, individuals Cys with values above the fifth quantile (>463.4 μmol/L) showed an increase of 0.59 in the mean score Z of BMI (p<0.01) and average increase of 5cm in the mean CC (p<0.01)29.

The possible mechanism by which the high concentration of serum Cys leads to excess body fat handle can be explained by the inhibition of lipolysis by hydrogen peroxide (H2O2) origin from the auto-oxidation of Cys and activating the lipogenesis34. In turn, auto-oxidation of Cys is related to changes in blood pressure, since it promotes the production of nitric oxide by the vascular endothelium (forming nitrosothiol), that leads to damage in the endothelium-dependent vasodilation mediated by nitric oxide8.

It is also noted that overweight is associated with the atherogenic lipid profile of low HDL-C and high triglycerides36. Therefore, it is possible that the relationship between the increase in Cys and dyslipidemia occurs through common overweight pathways that act directly or indirectly on the determination of the event. The pathophysiological mechanisms for this association have not yet been fully elucidated. The last etiological event - from experimental studies in vitro and in vivo - and that have received the adhesion of many researchers, indicate that high values of sulfhydryl amino acids increase the expression of SREBP-1 (protein binding to the regulatory element of sterol) - an important element in the path of cholesterol and triglyceride biosynthesis - favoring the appearance of changes in the lipid profile10.

In addition, studies have shown that the increase in concentrations of Cys inhibition in the transcription of the apolipoprotein A-1 with consequent reduction in the synthesis of HDL- c in hepatocytes and contribu yen to the occurrence and / or deepening dyslipidemia 28, 32. In addition, it is emphasized that Cys is a large functional and structural component of protein of the apolipoprotein B, protein L LDL cholesterol (LDL - c), which is the most important form of transport cholesterol from the liver to other tissues haci 10.

Costa et al.28 they identified that high level of Cys (>463.4 μmol/L ) is associated with low HDL- c levels (PR=1.15, p=0.01) and hypertriglyceridemia (PR=1.41, p=0 02). Also, in the study by Silva et al.13 children with high levels of LDL- c were twice chances as likely to have higher levels of cysteine (>445.0 μmol/L ), that is, there was no association between hypercysteinemia and high levels of LDL- c (21 2% versus 12.3%, p = 0.015) and normal levels of HDL-c (13.6% vs. 26.6%, p = 0.012).

Regarding the metabolism in the pathogenesis of IR and diabetes, recent discoveries suggest that the increasing or several amino acids is asociad at five times higher risk of developing diabetes after 12 years. The Cysplasma wasn´t measure, notwithstanding the high plasm ática cystine (the dimer not united to the protein that it constitutes approximately 25% plasma Cys) was observed in the study of insulin resistance and diabetes37. Due to its association with body fat, Cys can be a good predictor of insulin resistance in adolescents34.


CONCLUSIONS

The hypercysteinemine e hyperhomocysteinemia in Adolescents are associated with body adiposity, increased blood pressure, changes in serum lipid levels, such as reduction of HDL- c and increased LDL- C and triglycerides, and insulin resistance. Considering that the atherosclerotic process begins long before clinical aspects are detected, more studies with adolescents are still needed to identify the role of non-traditional riskmarkers for VCD, such as Hcy and Cys, including due to the importance of these amino acids in the development of already established components of the cardiovascular risk profile.


REFERENCES

1. Organização Pan-americana de Saúde. Determinantes Sociais e Riscos para a Saúde, Doenças Crônicas não transmissíveis e Saúde Mental. Doenças cardiovasculares. Brasília: OPAS, 2017. [acesso 2018 Mar 08]. Disponível em: http://www.paho.org/bra/index.php?option=com_content&view=article&id=5253:doencas-cardiovasculares&Itemid=839.

2. Sociedade Brasileira de Cardiologia. Cardiômetro da Sociedade Brasileira de Cardiologia, 2016. [acesso 2018 Mar 18]. Disponível em: http://socios.cardiol.br/2014/20160119-cardiometro.asp.

3. Raitakari OT, Juonala M, Kähönen M, Taittonen L, Laitinen T, Mäki-Torkko N, et al. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA. 2003 Nov 5;290(17):2277-83.

4. Berenson GS. Childhood risk factors predict adult risk associated with subclinical cardiovascular disease: The Bogalusa Heart Study. Am J Cardiol. 2002 Nov 21;90(10C):3L-7L.

5. Schmidt MI, Duncan BB, Silva GA, Menezes AM, Monteiro CA, Barreto SM et al. Doenças crônicas não transmissíveis no Brasil: carga e desafios atuais. In: Victora CG et al. Saúde no Brasil: a série The Lancet. Rio de Janeiro: Fiocruz; 2011. p. 61-74.

6. Nygård O, Vollset SE, Refsum H, Brattström L, Ueland PM. Total homocysteine and cardiovascular disease. J Intern Med. 1999 Nov;246(5):425-54.

7. Xiao and, Zhang and, Lv X, Su D, Li D, Xia M et al. Relationship between lipid profiles and plasma total homocysteine, cysteine and the risk of coronary artery disease in coronary angiographic subjects. Lipids Health Dis. 2011;10:137.

8. El-Khairy L, Ueland PM, Refsum H, Graham IM, Vollset SE. Plasma total cysteine as a risk factor for vascular disease - The European Concerted Action project. Circulation. 2001; 103: 2544-49.

9. Mccully KS. Vascular pathology of homocysteinemia: im-plications for the pathogenesis of arteriosclerosis. Am J Pathol. 1969 Jul;56(1):111-28.

10. Stipanuk MH. Homocysteine, cysteine, and taurine. In:Shils ME, Olson JA, Shike M, Ross AC, editors. Modern nutrition in health and disease. 10th ed. Baltimore: Lippincott Willians& Wilkins; 2006. p. 545-70.

11. Skovierová H, Vidomanová E, Mahmood S, Sopková J, Drgová A, Červeňová T et al. The Molecular and Cellular Effect of Homocysteine Metabolism Imbalance on Human Health. Int J Mol Sci. 2016 Oct 20;17(10).

12. Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, McPartlin J, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004;50:3-32.

13. Silva N, Souza F, Pendezza A, Fonseca F, Hix S, Oliveira A, et al. Homocysteine and cysteine levels in prepubertal children: Association with waist circumference and lipid profile. Nutrition. 2013;29:166-71.

14. Gil-Prieto R, Hernandez V, Cano B, Oya M, Gil A. Plasma homocysteine in adolescents depends on the interaction between methylenetetrahydrofolate reductase genotype, lipids and folate: a seroepidemiological study. Nutrition & Metabolism. 2009;6.

15. Leal AA, Simões MOS, Teixeira A, Medeiros CCM, Palmeira AC, Castro GMA et al. Homocysteine and Cardiovascular Risk Factors in Overweight or Obese Children and Adolescents. Health. 2015;7(3):381-389.

16. Anand P, Awasthi S, Mahdi A, Tiwari M, Agarwal GG. Serum homocysteine in Indian adolescents. Indian Journal of Pediatrics. 2009;76:705-09.

17. Akanji AO, Thalib L, Al-Isa AN. Folate, vitamin B12 and total homocysteine levels in Arab adolescent subjects: Reference ranges and potential determinants. Nutr Metab Cardiovasc Dis. 2012 Oct;22(10):900-6.

18. Papandreou D, Mavromichalis I, Makedou A, Rousso I, Arvanitidou M. Total serum homocysteine, folate and vitamin B12 in a Greek school age population. Clin Nutr 2006;25:797-802.

19. Casanueva VE, Cid XC, Cancino MM, Borzone LT, Cid LS. Homocisteínaenniños y adolescentes. Relación com historia familiar de enfermedad cardiovascular. Rev Méd Chile. 2003;131:997-1002.

20. Greenlund KJ, Srinivasan SR, Xu JH, Dalferes E Jr, Myers L, Pickoff A et al. Plasma homocysteine distribution and its association with parental history of coronary artery disease in black and white children - The Bogalusa Heart Study. Circulation. 1999 Apr 27;99(16):2144-9.

21. Pinto WJ, Areas MA, Marialva JE, Cardoso SMG, Pinto EG. Homocisteína e risco cardiovascular. Rev Ciênc Méd. 2009;18(5/6):259-268.

22. Zhu W, Huang X, Li M, Neubauer H. Elevated plasma homocysteine in obese schoolchildren with early atherosclerosis. Eur J Pediatr. 2005;5:33-8.

23. Brasileiro RS, Escrivao MA, Taddei JA, D'Almeida V, Ancona-Lopez F, Carvalhaes JT. Plasma total homocysteine in Brazilian overweight and non-overweight adolescents: a case-control study. Nutr Hosp. 2005; 20: 313-9.

24. Oshaug A, Bugge KH, Refsum H. Diet, an independent determinant for plasma total homocysteine: A cross sectional study of Norwegian Works on platforms in the North Sea. Eur J Clin Nutr. 1998 Jan;52(1):7-11.

25. Osganian SK, Stampfer MJ, Spiegelman D, Rim E, Cutler JA, Fekdman HÁ, et al. Distribution of and factors associated with serum homocysteine levels in children - Child and Adolescent Trial for Cardiovascular Health. Jama- Journalofthe American Medical Association. 1999; 281: 1189-96.

26. Papandreou D, Rousso I, Makedou A, Arvanitidou M, Mavromichalis I. Association of blood pressure, obesity and serum homocysteine levels in healthy children. Acta Paediatr 2007;96:1819e23.

27. Papandreou D, Mavromichalis I, Makedou A, Rousso I, Arvanitidou M. Reference range of total serum homocysteine level and dietary indexes in healthy Greek schoolchildren aged 6 e 15 years. Br J Nutr 2006;96:719e24.

28. Costa, PRD; Kinra, S; D'Almeida, V; Assis, AMO. Serum homocysteine and cysteine levels and associated factors in children and adolescentes. Nutr. clín. diet. hosp. 2017;37(1):106-116.

29. Costa PRF, Kinra S, D'Almeida V, Assis AMO. Serum Homocysteine and Cysteine Levels and Anthropometric Changes: A Longitudinal Study among Brazilian Children and Adolescents. J Am Coll Nutr. 2018 Jan;37(1):80-86.

30. Liao D, Yang X, Wang H. Hyperhomocysteinemia and high-density lipoprotein metabolism in cardiovascular disease. ClinicalChemistryandLaboratory Medicine. 2007; 45: 1652-59.

31. Shen MH, Chu NF, Wu DM. Chang JB. Plasma homocysteine, folate and vitamin B12 levels among school children in Taiwan: The Taipei Children Heart Study. Clin Biochem. 2002 Sep;35(6):495-8.

32. Costa PRF, Kinra S, D'Almeida V, Assis AMO. Serum homocysteine and cysteine levels and changes in the lipid profile of children and adolescents over a 12-month follow-up period. Clin Nutr ESPEN, 2017;21:13-19.

33. Patel RS, Al Mheid I, Morris AA, Ahmed and, Kavtaradze N, Ali S et al. Oxidative stress is associated with impaired arterial elasticity. Atherosclerosis. 2011 Sep;218(1):90-5.

34. Elshorbagy AK, Valdivia-Garcia M, Refsum H, Butte N. The Association of Cysteine with Obesity, Inflammatory Cytokines and Insulin Resistance in Hispanic Children and Adolescents. PlosOne. 2012; 7.

35. Elshorbagy AK, Gjesdal CG, Nurk E, Tell GS, Ueland PM, Nygård O et al. Cysteine, homocysteine and bone mineral density: a role for body composition? Bone. 2009 May;44(5):954-8.

36. Codoñer-Franch P, Murria-Estal R, Tortajada-Girbés M, del Castillo-Villaescusa C, Valls-Bellés V, Alonso-Iglesias E. New factors of cardiometabolic risk in severely obese children: influence of pubertal status. Nutr Hosp. 2010 Sep-Oct;25(5):845-51.

37. Fiehn O, Garvey WT, Newman JW, Lok KH, Hoppel CL, Adams SH. Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. PLoS One. 2010 Dec 10;5(12):e15234.
adolescencia adolescencia adolescencia
GN1 © 2004-2019 Revista Adolescência e Saúde. Fone: (21) 2868-8456 / 2868-8457
Núcleo de Estudos da Saúde do Adolescente - NESA - UERJ
Boulevard 28 de Setembro, 109 - Fundos - Pavilhão Floriano Stoffel - Vila Isabel, Rio de Janeiro, RJ. CEP: 20551-030.
E-mail: revista@adolescenciaesaude.com