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Amino Acids Mar 2020Taurine (a sulfur-containing β-amino acid), creatine (a metabolite of arginine, glycine and methionine), carnosine (a dipeptide; β-alanyl-L-histidine), and... (Review)
Review
Taurine (a sulfur-containing β-amino acid), creatine (a metabolite of arginine, glycine and methionine), carnosine (a dipeptide; β-alanyl-L-histidine), and 4-hydroxyproline (an imino acid; also often referred to as an amino acid) were discovered in cattle, and the discovery of anserine (a methylated product of carnosine; β-alanyl-1-methyl-L-histidine) also originated with cattle. These five nutrients are highly abundant in beef, and have important physiological roles in anti-oxidative and anti-inflammatory reactions, as well as neurological, muscular, retinal, immunological and cardiovascular function. Of particular note, taurine, carnosine, anserine, and creatine are absent from plants, and hydroxyproline is negligible in many plant-source foods. Consumption of 30 g dry beef can fully meet daily physiological needs of the healthy 70-kg adult human for taurine and carnosine, and can also provide large amounts of creatine, anserine and 4-hydroxyproline to improve human nutrition and health, including metabolic, retinal, immunological, muscular, cartilage, neurological, and cardiovascular health. The present review provides the public with the much-needed knowledge of nutritionally and physiologically significant amino acids, dipeptides and creatine in animal-source foods (including beef). Dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline are beneficial for preventing and treating obesity, cardiovascular dysfunction, and ageing-related disorders, as well as inhibiting tumorigenesis, improving skin and bone health, ameliorating neurological abnormalities, and promoting well being in infants, children and adults. Furthermore, these nutrients may promote the immunological defense of humans against infections by bacteria, fungi, parasites, and viruses (including coronavirus) through enhancing the metabolism and functions of monocytes, macrophages, and other cells of the immune system. Red meat (including beef) is a functional food for optimizing human growth, development and health.
Topics: Animals; Anserine; Carnosine; Cattle; Creatine; Humans; Hydroxyproline; Nutritive Value; Red Meat; Taurine
PubMed: 32072297
DOI: 10.1007/s00726-020-02823-6 -
Biochimica Et Biophysica Acta Feb 2007The absorption of zwitterionic imino and amino acids, and related drugs, is an essential function of the small intestinal epithelium. This review focuses on the... (Review)
Review
The absorption of zwitterionic imino and amino acids, and related drugs, is an essential function of the small intestinal epithelium. This review focuses on the physiological roles of transporters recently identified at the molecular level, in particular SLC36A1, by identifying how they relate to the classical epithelial imino and amino acid transporters characterised in mammalian small intestine in the 1960s-1990s. SLC36A1 transports a number of D- and L-imino and amino acids, beta- and gamma-amino acids and orally-active neuromodulatory and antibacterial agents. SLC36A1 (or PAT1) functions as a proton-coupled imino and amino acid symporter in cooperation with the Na+/H+ exchanger NHE3 (SLC9A3) to produce the imino acid carrier identified in rat small intestine in the 1960s but subsequently ignored because of confusion with the IMINO transporter. However, it is the sodium/imino and amino acid cotransporter SLC6A20 which corresponds to the betaine carrier (identified in hamster, 1960s) and IMINO transporter (identified in rabbit and guinea pig, 1980s). This review summarises evidence for expression of SLC36A1 and SLC6A20 in human small intestine, highlights the differences in functional characteristics of the imino acid carrier and IMINO transporter, and explains the confusion surrounding these two distinct transport systems.
Topics: Amino Acid Transport Systems; Amino Acids; Animals; Biological Transport, Active; Cell Membrane; Humans; Intestinal Mucosa; Symporters
PubMed: 17123464
DOI: 10.1016/j.bbamem.2006.10.001 -
Archives of Disease in Childhood Dec 1968
Topics: Amino Acid Metabolism, Inborn Errors; Diet Therapy; Humans; Hydroxyproline; Infant; Male; Proline
PubMed: 5702251
DOI: 10.1136/adc.43.232.748-a -
Antioxidants & Redox Signaling Sep 2013The imino acid proline is utilized by different organisms to offset cellular imbalances caused by environmental stress. The wide use in nature of proline as a stress... (Review)
Review
SIGNIFICANCE
The imino acid proline is utilized by different organisms to offset cellular imbalances caused by environmental stress. The wide use in nature of proline as a stress adaptor molecule indicates that proline has a fundamental biological role in stress response. Understanding the mechanisms by which proline enhances abiotic/biotic stress response will facilitate agricultural crop research and improve human health.
RECENT ADVANCES
It is now recognized that proline metabolism propels cellular signaling processes that promote cellular apoptosis or survival. Studies have shown that proline metabolism influences signaling pathways by increasing reactive oxygen species (ROS) formation in the mitochondria via the electron transport chain. Enhanced ROS production due to proline metabolism has been implicated in the hypersensitive response in plants, lifespan extension in worms, and apoptosis, tumor suppression, and cell survival in animals.
CRITICAL ISSUES
The ability of proline to influence disparate cellular outcomes may be governed by ROS levels generated in the mitochondria. Defining the threshold at which proline metabolic enzyme expression switches from inducing survival pathways to cellular apoptosis would provide molecular insights into cellular redox regulation by proline. Are ROS the only mediators of proline metabolic signaling or are other factors involved?
FUTURE DIRECTIONS
New evidence suggests that proline biosynthesis enzymes interact with redox proteins such as thioredoxin. An important future pursuit will be to identify other interacting partners of proline metabolic enzymes to uncover novel regulatory and signaling networks of cellular stress response.
Topics: Adaptation, Physiological; Metabolic Networks and Pathways; Oxidative Stress; Plants; Proline
PubMed: 23581681
DOI: 10.1089/ars.2012.5074 -
Laboratory Medicine Sep 2022The aim of the study was to evaluate proline metabolism in patients affected by COVID-19.
OBJECTIVE
The aim of the study was to evaluate proline metabolism in patients affected by COVID-19.
MATERIALS AND METHODS
This case-control study consisted of 116 patients with COVID-19 and 46 healthy individuals. Tests related to proline metabolism (prolidase, proline, hydroxyproline, glutamic acid, manganese) and copper and zinc tests were analyzed.
RESULTS
The levels of proline and hydroxyproline amino acids and the prolidase enzyme were found to be lower and glutamic acid was found to be higher in the COVID-19 group compared to the healthy group (P = .012, P < .001, P < .001, and P < .001, respectively). The copper/zinc ratio was higher in patients with COVID-19 than in healthy individuals (P < .001). Significant correlations were found between proline metabolism tests and inflammatory and hemostatic markers commonly used in COVID-19.
CONCLUSION
The proline metabolic pathway was affected in COVID-19. Relationships between proline pathway-related tests and inflammatory/hemostatic markers supported the roles of proline metabolism in proinflammatory and immune response processes.
Topics: COVID-19; Case-Control Studies; Copper; Dipeptidases; Glutamates; Hemostatics; Humans; Hydroxyproline; Proline; Zinc
PubMed: 35394547
DOI: 10.1093/labmed/lmac017 -
Journal of the American Chemical Society Sep 2021Peptides constrained by intramolecular cross-links, especially stapled α-helices, have emerged as versatile scaffolds for drug development. However, there are fewer...
Peptides constrained by intramolecular cross-links, especially stapled α-helices, have emerged as versatile scaffolds for drug development. However, there are fewer examples of similarly constrained scaffolds for other secondary structures. Here, we used a novel computational strategy to identify an optimal staple for antiparallel β-strands, and then we incorporated that staple within a β-hairpin peptide. The hairpin uses 4-mercaptoproline as a novel staple component, which contributes to a unique, kinked structure. The stapled hairpins show a high degree of structure in aqueous solution, excellent resistance to degradation in cell lysates, and cytosolic penetration at micromolar concentrations. They also overlay with a unique subset of kinked hairpin motifs at protein-protein interaction interfaces. Thus, these scaffolds represent promising starting points for developing inhibitors of cellular protein-protein interactions.
Topics: Amino Acid Sequence; Models, Molecular; Peptides; Proline; Protein Structure, Secondary
PubMed: 34516087
DOI: 10.1021/jacs.1c04378 -
Journal of Neuropathology and... May 2022The naturally occurring imino acid azetidine-2-carboxylic acid (Aze) is consumed by humans and can be misincorporated in place of proline in myelin basic protein (MBP)...
The naturally occurring imino acid azetidine-2-carboxylic acid (Aze) is consumed by humans and can be misincorporated in place of proline in myelin basic protein (MBP) in vitro. To determine Aze effects on the mammalian CNS in vivo, adult CD1 mice were given Aze orally or intraperitoneally. Clinical signs reminiscent of MBP-mutant mice occurred with 600 mg/kg Aze exposure. Aze induced oligodendrocyte (OL) nucleomegaly and nucleoplasm clearing, dilated endoplasmic reticulum, cytoplasmic vacuolation, abnormal mitochondria, and Aze dose-dependent apoptosis. Immunohistochemistry demonstrated myelin blistering and nuclear translocation of unfolded protein response (UPR)/proinflammatory molecules (ATF3, ATF4, ATF6, eIF2α, GADD153, NFκB, PERK, XBP1), MHC I expression, and MBP cytoplasmic aggregation in OL. There were scattered microglial nodules in CNS white matter (WM); other CNS cells appeared unaffected. Mice given Aze in utero and postnatally showed more marked effects than their dams. These OL, myelin, and microglial alterations are found in normal-appearing WM (NAWM) in multiple sclerosis (MS) patients. Thus, Aze induces a distinct oligodendrogliopathy in mice that recapitulates MS NAWM pathology without leukocyte infiltration. Because myelin proteins are relatively stable throughout life, we hypothesize that Aze misincorporation in myelin proteins during myelinogenesis in humans results in a progressive UPR that may be a primary process in MS pathogenesis.
Topics: Animals; Azetidinecarboxylic Acid; Humans; Mammals; Mice; Multiple Sclerosis; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; Proline
PubMed: 35521963
DOI: 10.1093/jnen/nlac028 -
Cardiology Journal 2022Current hypertension guidelines suggest various strategies to reduce blood pressure levels, thereby reducing cardiovascular events: combinations of drugs with different...
Current hypertension guidelines suggest various strategies to reduce blood pressure levels, thereby reducing cardiovascular events: combinations of drugs with different mechanisms of action, such as an angiotensin converting enzyme inhibitors (ACEIs) and a diuretic, are the cornerstone of the modern treatment of hypertension, also as initial therapy. Among ACEIs, zofenopril has been shown to be effective in the management of hypertension both as monotherapy and in combination with a diuretic: zofenopril/hydrochlorothiazide fixed dose combination is particularly useful to improve treatment adherence through simplification of treatment regimen. Moreover, thanks to the sulfhydryl group, zofenopril has some peculiar properties (higher lipophilicity and tissue penetration, lower bradykinin-dependent effect, higher affinity for, and more persistent binding to, tissue ACE, significant antioxidant effect), which may account for the cardioprotective effects of the drug demonstrated in both pre-clinical studies and randomized clinical trials. The positive impact of zofenopril on clinical outcomes has been extensively documented by the SMILE program, including several clinical trials in patients with different conditions of myocardial ischemia treated with zofenopril: the results of the SMILE program, demonstrating the benefits of zofenopril vs. placebo and other ACEIs, emphasize the importance of a differentiated approach to patients with ischemic heart disease, based on a careful choice of the adopted agent, in order to improve the overall impact of pharmacological treatment on clinical outcomes.
Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Captopril; Diuretics; Humans; Hypertension; Myocardial Ischemia
PubMed: 34622438
DOI: 10.5603/CJ.a2021.0113 -
Antioxidants & Redox Signaling Feb 2019Proline metabolism has complex roles in a variety of biological processes, including cell signaling, stress protection, and energy production. Proline also contributes... (Review)
Review
SIGNIFICANCE
Proline metabolism has complex roles in a variety of biological processes, including cell signaling, stress protection, and energy production. Proline also contributes to the pathogenesis of various disease-causing organisms. Understanding the mechanisms of how pathogens utilize proline is important for developing new strategies against infectious diseases. Recent Advances: The ability of pathogens to acquire amino acids is critical during infection. Besides protein biosynthesis, some amino acids, such as proline, serve as a carbon, nitrogen, or energy source in bacterial and protozoa pathogens. The role of proline during infection depends on the physiology of the host/pathogen interactions. Some pathogens rely on proline as a critical respiratory substrate, whereas others exploit proline for stress protection.
CRITICAL ISSUES
Disruption of proline metabolism and uptake has been shown to significantly attenuate virulence of certain pathogens, whereas in other pathogens the importance of proline during infection is not known. Inhibiting proline metabolism and transport may be a useful therapeutic strategy against some pathogens. Developing specific inhibitors to avoid off-target effects in the host, however, will be challenging. Also, potential treatments that target proline metabolism should consider the impact on intracellular levels of Δ-pyrroline-5-carboxylate, a metabolite intermediate that can have opposing effects on pathogenesis.
FUTURE DIRECTIONS
Further characterization of how proline metabolism is regulated during infection would provide new insights into the role of proline in pathogenesis. Biochemical and structural characterization of proline metabolic enzymes from different pathogens could lead to new tools for exploring proline metabolism during infection and possibly new therapeutic compounds.
Topics: Animals; Host-Pathogen Interactions; Humans; Oxidation-Reduction; Proline
PubMed: 29241353
DOI: 10.1089/ars.2017.7335 -
Analytical Biochemistry Jun 2024Prolidase (EC.3.4.13.9) is a dipeptidase known nowadays to play a pivotal role in several physiological and pathological processes. More in particular, this enzyme is... (Review)
Review
Prolidase (EC.3.4.13.9) is a dipeptidase known nowadays to play a pivotal role in several physiological and pathological processes. More in particular, this enzyme is involved in the cleavage of proline- and hydroxyproline-containing dipeptides (imidodipeptides), thus finely regulating the homeostasis of free proline and hydroxyproline. Abnormally high or low levels of prolidase have been found in numerous acute and chronic syndromes affecting humans (chronic liver fibrosis, viral and acute hepatitis, cancer, neurological disorders, inflammation, skin diseases, intellectual disability, respiratory infection, and others) for which the content of proline is well recognized as a clinical marker. As a consequence, the accurate analytical determination of prolidase activity is of greatly significant importance in clinical diagnosis and therapy. Apart from the Chinard's assay, some other more sensitive and well validated methodologies have been published. These include colorimetric and spectrophotometric determinations of free proline produced by enzymatic reactions, capillary electrophoresis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, electrochemoluminescence, thin layer chromatography, and HPLC. The aim of this comprehensive review is to make a detailed survey of the in so far reported analytical techniques, highlighting their general features, as well as their advantages and possible drawbacks, providing in the meantime suggestions to stimulate further research in this intriguing field.
Topics: Humans; Colorimetry; Dipeptidases; Fibrosis; Hydroxyproline; Proline; Enzyme Assays
PubMed: 38460899
DOI: 10.1016/j.ab.2024.115506