File Name: discuss the significance of vitamin c to carnitine and fat metabolism ncbi.zip
Age-related loss of skeletal muscle mass contributes to poor outcomes including sarcopenia, physical disability, frailty, type 2 diabetes, and mortality. Vitamin C has physiological relevance to skeletal muscle and may protect it during aging, but few studies have investigated its importance in older populations.
- Vitamin C: A Review on its Role in the Management of Metabolic Syndrome
- Vitamin C and Immune Function
- Acetyl-CoA carboxylase
- Fatty acid oxidation disorders
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.
Vitamin C: A Review on its Role in the Management of Metabolic Syndrome
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. AB lies within BC. Biotin is covalently attached through an amide bond to the long side chain of a lysine reside in BB. In mammals where two isoforms of ACC are expressed, the main structural difference between these isoforms is the extended ACC2 N-terminus containing a mitochondrial targeting sequence.
The polypeptides composing the multi-subunit ACCs of prokaryotes and plants are encoded by distinct genes. In Escherichia coli , accA encodes the alpha subunit of the acetyl-CoA carboxylase,  and accD encodes its beta subunit. The carboxyl group is transferred from biotin to acetyl CoA to form malonyl CoA in the second reaction, which is catalyzed by CT. In the active site , the reaction proceeds with extensive interaction of the residues Glu and positively charged Arg and Arg with the substrates.
Bicarbonate is deprotonated by Glu, although in solution, this proton transfer is unlikely as the pKa of bicarbonate is The enzyme apparently manipulates the pKa to facilitate the deprotonation of bicarbonate. The pKa of bicarbonate is decreased by its interaction with positively charged side chains of Arg and Arg Furthermore, Glu interacts with the side chain of Glu, an interaction that has been shown to cause an increase in the apparent pKa.
Following deprotonation of bicarbonate, the oxygen of the bicarbonate acts as a nucleophile and attacks the gamma phosphate on ATP. In contrast to the BC domain, little is known about the reaction mechanism of CT.
A proposed mechanism is the release of CO 2 from biotin, which subsequently abstracts a proton from the methyl group from acetyl CoA carboxylase. The resulting enolate attacks CO 2 to form malonyl CoA. In a competing mechanism, proton abstraction is concerted with the attack of acetyl CoA. The function of ACC is to regulate the metabolism of fatty acids. When the enzyme is active, the product, malonyl-CoA, is produced which is a building block for new fatty acids and can inhibit the transfer of the fatty acyl group from acyl CoA to carnitine with carnitine acyltransferase , which inhibits the beta-oxidation of fatty acids in the mitochondria.
ACC1 is found in the cytoplasm of all cells but is enriched in lipogenic tissue, such as adipose tissue and lactating mammary glands , where fatty acid synthesis is important. ACC1 and ACC2 are both highly expressed in the liver where both fatty acid oxidation and synthesis are important.
The regulation of mammalian ACC is complex, in order to control two distinct pools of malonyl CoA that direct either the inhibition of beta oxidation or the activation of lipid biosynthesis. Activation of gene expression through different promoters results in alternative splicing ; however, the physiological significance of specific ACC isozymes remains unclear. Through a feed-forward loop, citrate allosterically activates ACC.
Other allosteric activators include glutamate and other dicarboxylic acids. Phosphorylation can result when the hormones glucagon or epinephrine bind to cell surface receptors , but the main cause of phosphorylation is due to a rise in AMP levels when the energy status of the cell is low, leading to the activation of the AMP-activated protein kinase AMPK.
However, the physiological significance of protein kinase A in the regulation of ACC is currently unknown. Researchers hypothesize there are other ACC kinases important to its regulation as there are many other possible phosphorylation sites on ACC.
When insulin binds to its receptors on the cellular membrane , it activates a phosphatase enzyme called protein phosphatase 2A PP2A to dephosphorylate the enzyme; thereby removing the inhibitory effect. This protein may use the morpheein model of allosteric regulation. At the juncture of lipid synthesis and oxidation pathways, ACC presents many clinical possibilities for the production of novel antibiotics and the development of new therapies for diabetes , obesity , and other manifestations of metabolic syndrome.
Promising results for the usefulness of an ACC inhibitor include the finding that mice with no expression of ACC2 have continuous fatty acid oxidation, reduced body fat mass, and reduced body weight despite an increase in food consumption. These mice are also protected from diabetes.
In addition, plant-selective ACC inhibitors are in widespread use as herbicides ,  which suggests clinical application against Apicomplexa parasites that rely on a plant-derived ACC isoform,  including malaria. From Wikipedia, the free encyclopedia. An enzyme that regulates the metabolism of fatty acids.
Crystallographic structures of E. Biotin carboxylase subunit of E. Biotin carboxyl carrier protein subunit of E. Carboxyl transferase subunit of E. Cellular and Molecular Life Sciences.
Biochemical Society Transactions. Bibcode : PNAS The Biochemical Journal. Bioscience, Biotechnology, and Biochemistry. K substr. MG ". NCBI gene. National Center for Biotechnology Information, U. National Library of Medicine. The Journal of Biological Chemistry. Biochemical and Biophysical Research Communications. Bibcode : Sci Bibcode : PNAS.. Journal of Applied Physiology. Archives of Biochemistry and Biophysics.
Recent Patents on Cardiovascular Drug Discovery. Endpoints News. Clinical and Experimental Hepatology. Herbicide Symptoms. Voet D, Voet JG Biochemistry and molecular biology of plants. American Society of Plant Physiologists. Stearoyl-CoA desaturase Glycerolphosphate dehydrogenase Thiokinase. Carnitine palmitoyltransferase I Carnitine-acylcarnitine translocase Carnitine palmitoyltransferase II. Propionyl-CoA carboxylase. Hydroxyacyl-Coenzyme A dehydrogenase.
Malonyl-CoA decarboxylase. Long-chain-aldehyde dehydrogenase. Ligases : carbon-carbon ligases EC 6. Polyketide synthase. Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator.
EC number Enzyme superfamily Enzyme family List of enzymes. Biology portal. Categories : Genes on human chromosome 17 Genes on human chromosome 12 EC 6.
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Vitamin C and Immune Function
Fatty acid oxidation disorders FAODs lead to deficient energy production and produce three variable clinical presentations in all ages. Typically the most severe life-threatening presentations may rapidly occur within a few hours of fasting in infants, but adults may require up to 48 hours of fasting. The neonatal-onset type, where newborns will develop a profound cardiomyopathy, hypoketotic hypoglycemia, and liver dysfunction within the first few days or weeks of life, is often fatal. The infantile-onset type will present in infancy or childhood with intermittent episodes of lethargy and vomiting associated with intercurrent illnesses and lead to hepatic dysfunction, hypoketotic hypoglycemia, and encephalopathy or sudden death. The later- or adolescent or adult- onset myopathic type presents with episodes of muscle weakness, myalgias, rhabdomyolysis, and risk of renal damage. There is an estimated collective incidence of one in 5,—10, births, although the individual prevalence varies significantly Table 1 9.
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. Objectives: The current study aimed to evaluate the effect of L-carnitine supplementation with low-calorie diet on the metabolic status in obese women with type II diabetes. Patients and Methods: In this study, 60 obese premenopausal women with type II diabetes were randomly selected from the patients who referred to the Diabetes Clinic of Tabriz Red Crescent; they were 20 - 50 years old with a BMI greater than
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. In vivo studies showed promising effects of vitamin C, but most of the interventions used were in combination with other compounds. The direct effects of vitamin C remain to be elucidated.
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.
Fatty acid oxidation disorders
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. By maintaining enzyme-bound metals in their reduced forms, vitamin C assists mixed-function oxidases in the synthesis of several critical biomolecules 1. These enzymes are either monooxygenases or dioxygenases see Table 1.
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. Studies in older adults further showed that l -carnitine intake can lead to increased muscle mass accompanied by a decrease in body weight and reduced physical and mental fatigue.