File Name: discuss the significance of vitamin c to carnitine and fat metabolism ncbi.zip
Box , Christchurch , New Zealand.
- Vitamin C and Immune Function
- Vitamin C: A Review on its Role in the Management of Metabolic Syndrome
- Acetyl-CoA carboxylase
Background: More than million people worldwide are obese and around million adults have type II diabetes, thus these two diseases are accounted as the fundamental health care problems. There is such a strong association between obesity and diabetes that the term diabesity is proposed for this connection. Since anti-obesity drugs have many side effects, experts have very few tools to fight obesity, while high doses of carnitine has no side effects compared to other drugs.
Vitamin C and Immune Function
Box , Christchurch , New Zealand. Vitamin C is an essential micronutrient for humans, with pleiotropic functions related to its ability to donate electrons.
It is a potent antioxidant and a cofactor for a family of biosynthetic and gene regulatory enzymes. Vitamin C contributes to immune defense by supporting various cellular functions of both the innate and adaptive immune system.
Vitamin C supports epithelial barrier function against pathogens and promotes the oxidant scavenging activity of the skin, thereby potentially protecting against environmental oxidative stress.
Vitamin C accumulates in phagocytic cells, such as neutrophils, and can enhance chemotaxis, phagocytosis, generation of reactive oxygen species, and ultimately microbial killing. The role of vitamin C in lymphocytes is less clear, but it has been shown to enhance differentiation and proliferation of B- and T-cells, likely due to its gene regulating effects.
Vitamin C deficiency results in impaired immunity and higher susceptibility to infections. In turn, infections significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements.
Furthermore, supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate, if not saturating plasma levels i. In contrast, treatment of established infections requires significantly higher gram doses of the vitamin to compensate for the increased inflammatory response and metabolic demand. The immune system is a multifaceted and sophisticated network of specialized organs, tissues, cells, proteins, and chemicals, which has evolved in order to protect the host from a range of pathogens, such as bacteria, viruses, fungi, and parasites, as well as cancer cells [ 1 ].
It can be divided into epithelial barriers, and cellular and humoral constituents of either innate non-specific and acquired specific immunity [ 1 ]. These constituents interact in multiple and highly complex ways.
More than half a century of research has shown vitamin C to be a crucial player in various aspects of the immune system, particularly immune cell function [ 2 , 3 ]. Vitamin C is an essential nutrient which cannot be synthesized by humans due to loss of a key enzyme in the biosynthetic pathway [ 4 , 5 ]. Severe vitamin C deficiency results in the potentially fatal disease scurvy [ 6 ].
Scurvy is characterized by weakening of collagenous structures, resulting in poor wound healing, and impaired immunity. Individuals with scurvy are highly susceptible to potentially fatal infections such as pneumonia [ 7 ]. In turn, infections can significantly impact on vitamin C levels due to enhanced inflammation and metabolic requirements.
Early on, it was noted that scurvy often followed infectious epidemics in populations [ 7 ], and cases of scurvy have been reported following respiratory infection [ 8 ]. This is particularly apparent for individuals who are already malnourished. Although the amount of vitamin C required to prevent scurvy is relatively low i.
Due to the low storage capacity of the body for the water-soluble vitamin, a regular and adequate intake is required to prevent hypovitaminosis C. There are several reasons why vitamin C dietary recommendations are not met, even in countries where food availability and supply would be expected to be sufficient.
Vitamin C has a number of activities that could conceivably contribute to its immune-modulating effects. It is a highly effective antioxidant, due to its ability to readily donate electrons, thus protecting important biomolecules proteins, lipids, carbohydrates, and nucleic acids from damage by oxidants generated during normal cell metabolism and through exposure to toxins and pollutants e.
Vitamin C is also a cofactor for a family of biosynthetic and gene regulatory monooxygenase and dioxygenase enzymes [ 18 , 19 ]. The vitamin has long been known as a cofactor for the lysyl and prolyl hydroxylases required for stabilization of the tertiary structure of collagen, and is a cofactor for the two hydroxylases involved in carnitine biosynthesis, a molecule required for transport of fatty acids into mitochondria for generation of metabolic energy Figure 1 [ 19 ].
The enzyme cofactor activities of vitamin C. Vitamin C is a cofactor of a family of biosynthetic and gene regulatory monooxygenase and dioxygenase enzymes. These enzymes are involved in the synthesis of collagen, carnitine, catecholamine hormones, e.
These enzymes also hydroxylate transcription factors, e. Vitamin C is also a cofactor for the hydroxylase enzymes involved in the synthesis of catecholamine hormones, e. Furthermore, research over the past 15 years or so has uncovered new roles for vitamin C in the regulation of gene transcription and cell signaling pathways through regulation of transcription factor activity and epigenetic marks Figure 1 [ 21 , 22 ].
Recent research has also indicated an important role for vitamin C in regulation of DNA and histone methylation by acting as a cofactor for enzymes which hydoxylate these epigenetic marks [ 22 ]. Our review explores the various roles of vitamin C in the immune system, including barrier integrity and leukocyte function, and discusses potential mechanisms of action.
We discuss the relevance of the immune-modulating effects of vitamin C in the context of infections and conditions leading to vitamin C insufficiency. The skin has numerous essential functions, the primary of which is to act as a barrier against external insults, including pathogens. The epidermal layer is highly cellular, comprising primarily keratinocytes, whilst the dermal layer comprises fibroblasts which secrete collagen fibers, the major component of the dermis [ 23 ].
Skin contains millimolar concentrations of vitamin C, with higher levels found in the epidermis than the dermis [ 24 , 25 , 26 ]. Vitamin C is actively accumulated into the epidermal and dermal cells via the two sodium-dependent vitamin C transporter SVCT isoforms 1 and 2 [ 27 ], suggesting that the vitamin has crucial functions within the skin.
Clues to the role of vitamin C in the skin come from the symptoms of the vitamin C deficiency disease scurvy, which is characterized by bleeding gums, bruising, and impaired wound healing [ 28 , 29 ]. These symptoms are thought to be a result of the role of vitamin C as a co-factor for the prolyl and lysyl hydroxylase enzymes that stabilize the tertiary structure of collagen Table 1 [ 30 ].
Further research has shown that vitamin C can also increase collagen gene expression in fibroblasts [ 31 , 32 , 33 , 34 , 35 ]. Note that many of these studies comprised marginal or deficient vitamin C status at baseline. Supplementation in situations of adequate vitamin C status may not have comparable effects. Vitamin C intervention studies in humans using both dietary and gram doses of vitamin C have shown enhanced vitamin C uptake into skin cells [ 26 , 36 ] and enhanced oxidant scavenging activity of the skin [ 36 , 37 ].
The elevated antioxidant status of the skin following vitamin C supplementation could potentially protect against oxidative stress induced by environmental pollutants [ 38 , 39 ]. The antioxidant effects of vitamin C are likely to be enhanced in combination with vitamin E [ 40 , ]. Cell culture and preclinical studies have indicated that vitamin C can enhance epithelial barrier functions via a number of different mechanisms.
Vitamin C supplementation of keratinocytes in culture enhances differentiation and barrier function via modulating signaling and biosynthetic pathways, with resultant elevations in barrier lipid synthesis [ 41 , 42 , 43 , 44 , 45 ].
Dysfunctional epithelial barrier function in the lungs of animals with serious infection can be restored by administration of vitamin C [ 74 ]. This was attributed to enhanced expression of tight junction proteins and prevention of cytoskeletal rearrangements. Animal studies using the vitamin C-dependent Gulo knockout mouse indicated that deficiency did not affect the formation of collagen in the skin of unchallenged mice [ ]; however, following full thickness excisional wounding there was significantly decreased collagen formation in vitamin C-deficient mice [ 46 ].
This finding is in agreement with an earlier study carried out with scorbutic guinea pigs [ ]. Thus, vitamin C appears to be particularly essential during wound healing, also decreasing the expression of pro-inflammatory mediators and enhancing the expression of various wound healing mediators [ 46 ]. Fibroblast cell culture experiments have also indicated that vitamin C can alter gene expression profiles within dermal fibroblasts, promoting fibroblast proliferation and migration which is essential for tissue remodeling and wound healing [ 46 , 47 ].
Following surgery, patients require relatively high intakes of vitamin C in order to normalize their plasma vitamin C status e. Leukocytes, particularly neutrophils and monocyte-derived macrophages, are major players in wound healing [ ].
During the initial inflammatory stage, neutrophils migrate to the wound site in order to sterilize it via the release of reactive oxygen species ROS and antimicrobial proteins [ ]. The neutrophils eventually undergo apoptosis and are cleared by macrophages, resulting in resolution of the inflammatory response.
However, in chronic, non-healing wounds, such as those observed in diabetics, the neutrophils persist and instead undergo necrotic cell death which can perpetuate the inflammatory response and hinder wound healing [ , ]. Vitamin C is thought to influence several important aspects of neutrophil function: migration in response to inflammatory mediators chemotaxis , phagocytosis and killing of microbes, and apoptosis and clearance by macrophages see below.
Leukocytes, such as neutrophils and monocytes, actively accumulate vitamin C against a concentration gradient, resulting in values that are to fold higher than plasma concentrations [ , , ].
Following stimulation of their oxidative burst neutrophils can further increase their intracellular concentration of vitamin C through the non-specific uptake of the oxidized form, dehydroascorbate DHA , via glucose transporters GLUT [ , ].
DHA is then rapidly reduced to ascorbate intracellularly, to give levels of about 10 mM [ ]. It is believed that the accumulation of such high vitamin C concentrations indicates important functions within these cells. Accumulation of millimolar concentrations of vitamin C into neutrophils, particularly following activation of their oxidative burst, is thought to protect these cells from oxidative damage [ ]. Vitamin C is a potent water-soluble antioxidant that can scavenge numerous reactive oxidants and can also regenerate the important cellular and membrane antioxidants glutathione and vitamin E [ ].
Upon phagocytosis or activation with soluble stimulants, vitamin C is depleted from neutrophils in an oxidant-dependent manner [ 50 , 51 , 52 , 53 ]. Thiol-containing proteins can be particularly sensitive to redox alterations within cells and are often central to the regulation of redox-related cell signaling pathways [ ].
Vitamin C-dependent modulation of thiol-dependent cell signaling and gene expression pathways has been reported in T-cells [ , ]. Thus, vitamin C could modulate immune function through modulation of redox-sensitive cell signaling pathways or by directly protecting important cell structural components. For example, exposure of neutrophils to oxidants can inhibit motility of the cells, which is thought to be due to oxidation of membrane lipids and resultant effects on cell membrane fluidity [ 63 ].
Neutrophils contain high levels of polyunsaturated fatty acids in their plasma membranes, and thus improvements in neutrophil motility observed following vitamin C administration see below could conceivably be attributed to oxidant scavenging as well as regeneration of vitamin E [ ]. Neutrophil infiltration into infected tissues is an early step in innate immunity. In response to pathogen- or host-derived inflammatory signals e. Migration of neutrophils in response to chemical stimuli is termed chemotaxis, while random migration is termed chemokinesis Figure 2.
Neutrophils express more than 30 different chemokine and chemoattractant receptors in order to sense and rapidly respond to tissue damage signals [ ]. Early studies carried out in scorbutic guinea pigs indicated impaired leukocyte chemotactic response compared with leukocytes isolated from guinea pigs supplemented with adequate vitamin C in their diet Table 1 [ 54 , 55 , 56 , 64 ].
These findings suggest that vitamin C deficiency may impact on the ability of phagocytes to migrate to sites of infection. Role of vitamin C in phagocyte function. Vitamin C has been shown to: a enhance neutrophil migration in response to chemoattractants chemotaxis , b enhance engulfment phagocytosis of microbes, and c stimulate reactive oxygen species ROS generation and killing of microbes.
Patients with severe infection exhibit compromised neutrophil chemotactic ability [ , , , ]. However, it is also possible that vitamin C depletion, which is prevalent during severe infection [ 20 ], may contribute. Studies in the s and s indicated that patients with recurrent infections had impaired leukocyte chemotaxis, which could be restored in response to supplementation with gram doses of vitamin C [ 57 , 58 , 59 , 60 , 65 , 66 , 67 ].
Recurrent infections can also result from genetic disorders of neutrophil function, such as chronic granulomatous disease CGD , an immunodeficiency disease resulting in defective leukocyte generation of ROS [ ], and Chediak-Higashi syndrome CHS , a rare autosomal recessive disorder affecting vesicle trafficking [ ].
Although vitamin C administration would not be expected to affect the underlying defects of these genetic disorders, it may support the function of redundant antimicrobial mechanisms in these cells.
For example, patients with CGD showed improved leukocyte chemotaxis following supplementation with gram doses of vitamin C administered either enterally or parenterally [ , , ].
This was associated with decreased infections and clinical improvement [ , ]. The vitamin C-dependent enhancement of chemotaxis was thought to be mediated in part via effects on microtubule assembly [ , ], and more recent research has indicated that intracellular vitamin C can stabilize microtubules [ ]. Supplementation of healthy volunteers with dietary or gram doses of vitamin C has also been shown to enhance neutrophil chemotactic ability [ 61 , 62 , 63 , ].
Johnston et al. In participants who had inadequate vitamin C status i. Thus, members of the general population may benefit from improved immune cell function through enhanced vitamin C intake, particularly if they have inadequate vitamin C status, which can be more prevalent in the elderly. However, it should be noted that it is not yet certain to what extent improved ex vivo leukocyte chemotaxis translates into improved in vivo immune function.
Once neutrophils have migrated to the site of infection, they proceed to engulf the invading pathogens Figure 2.
Vitamin C: A Review on its Role in the Management of Metabolic Syndrome
Vitamin C is a cofactor in the biosynthesis of carnitine, a molecule required for the oxidation of fatty acids. A reduction in the ability to oxidize fat may contribute to the reported inverse relationship between vitamin C status and adiposity. To examine this possibility, we conducted a preliminary trial to evaluate the impact of vitamin C status on fat oxidation during submaximal exercise. Subsequently, eight of the subjects with marginal vitamin C status completed an 8-week double-blind, placebo-controlled, depletion-repletion trial with submaximal exercise testing. These preliminary results show that low vitamin C status is associated with reduced fat oxidation during submaximal exercise. Low vitamin C status may partially explain the inverse relationship between vitamin C status and adiposity and why some individuals are unsuccessful in their weight loss attempts.
Given its pivotal role in fatty acid oxidation and energy metabolism, l -carnitine has been investigated as ergogenic aid for enhancing exercise capacity in the healthy athletic population. Early research indicates its beneficial effects on acute physical performance, such as increased maximum oxygen consumption and higher power output. Later studies point to the positive impact of dietary supplementation with l -carnitine on the recovery process after exercise. It is demonstrated that l -carnitine alleviates muscle injury and reduces markers of cellular damage and free radical formation accompanied by attenuation of muscle soreness. The supplementation-based increase in serum and muscle l -carnitine contents is suggested to enhance blood flow and oxygen supply to the muscle tissue via improved endothelial function thereby reducing hypoxia-induced cellular and biochemical disruptions.
Vitamin C L-ascorbic acid is a potent reducing agent, meaning that it readily donates electrons to recipient molecules Figure 1. Vitamin C is the primary water-soluble, non-enzymatic antioxidant in plasma and tissues. Even in small amounts, vitamin C can protect indispensable molecules in the body, such as proteins , lipids fats , carbohydrates , and nucleic acids DNA and RNA , from damage by free radicals and reactive oxygen species ROS that are generated during normal metabolism , by active immune cells, and through exposure to toxins and pollutants e. Vitamin C also participates in redox recycling of other important antioxidants; for example, vitamin C is known to regenerate vitamin E from its oxidized form see the article on Vitamin E. The role of vitamin C as a cofactor is also related to its redox potential.
Vitamins are the organic compounds required by the human body and are considered as vital nutrients needed in specific amounts. They cannot be synthesized in a sufficient amount by the human body; so, they must be obtained from the diet. Thirteen different types of vitamins are known that are classified by their biological and chemical activity. Each one of them has a specific role in our body. Folic acid has a vital role in cell growth and development through many reactions and processes that occur in the body, e.
Oxidative stress and inflammation are two interlinked events that exist simultaneously in metabolic syndrome MetS and its related complications. These pathophysiological processes can be easily triggered by each other. This review summarizes the current evidence from animal and human studies on the effects of vitamin C in managing MetS.
ACC is a multi-subunit enzyme in most prokaryotes and in the chloroplasts of most plants and algae, whereas it is a large, multi-domain enzyme in the cytoplasm of most eukaryotes. The most important function of ACC is to provide the malonyl-CoA substrate for the biosynthesis of fatty acids. Prokaryotes and plants have multi-subunit ACCs composed of several polypeptides. The stoichiometry of these subunits in the ACC holoenzyme differs amongst organisms. Most plants also have this homomeric form in cytosol.
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