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Article ; Online: Histidine Metabolism and Function.

Brosnan, Margaret E / Brosnan, John T

2020 Volume 150, Issue Suppl 1, Page(s) 2570S–2575S

Abstract: Histidine is a dietary essential amino acid because it cannot be synthesized in humans. The WHO/FAO requirement for adults for histidine is 10 mg · kg body weight-1 · d-1. Histidine is required for synthesis of proteins. It plays particularly important ... ...

Abstract	Histidine is a dietary essential amino acid because it cannot be synthesized in humans. The WHO/FAO requirement for adults for histidine is 10 mg · kg body weight-1 · d-1. Histidine is required for synthesis of proteins. It plays particularly important roles in the active site of enzymes, such as serine proteases (e.g., trypsin) where it is a member of the catalytic triad. Excess histidine may be converted to trans-urocanate by histidine ammonia lyase (histidase) in liver and skin. UV light in skin converts the trans form to cis-urocanate which plays an important protective role in skin. Liver is capable of complete catabolism of histidine by a pathway which requires folic acid for the last step, in which glutamate formiminotransferase converts the intermediate N-formiminoglutamate to glutamate, 5,10 methenyl-tetrahydrofolate, and ammonia. Inborn errors have been recognized in all of the catabolic enzymes of histidine. Histidine is required as a precursor of carnosine in human muscle and parts of the brain where carnosine appears to play an important role as a buffer and antioxidant. It is synthesized in the tissue by carnosine synthase from histidine and β-alanine, at the expense of ATP hydrolysis. Histidine can be decarboxylated to histamine by histidine decarboxylase. This reaction occurs in the enterochromaffin-like cells of the stomach, in the mast cells of the immune system, and in various regions of the brain where histamine may serve as a neurotransmitter.
MeSH term(s)	Brain/metabolism ; Carnosine/metabolism ; Glutamic Acid/metabolism ; Histamine/metabolism ; Histidine/metabolism ; Histidine Ammonia-Lyase/metabolism ; Humans ; Liver/metabolism ; Muscles/metabolism ; Skin/metabolism
Chemical Substances	Glutamic Acid (3KX376GY7L) ; Histidine (4QD397987E) ; Histamine (820484N8I3) ; Carnosine (8HO6PVN24W) ; Histidine Ammonia-Lyase (EC 4.3.1.3)
Language	English
Publishing date	2020-09-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1093/jn/nxaa079
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Article ; Online: Formate and its role in amino acid metabolism.

Brosnan, John T / Brosnan, Margaret E

Current opinion in clinical nutrition and metabolic care

2019 Volume 23, Issue 1, Page(s) 23–28

Abstract: Purpose of review: The aim of this report is to examine critical relationships between amino acid and formate metabolism with particular reference to the production of formate, and to review novel functions of formate.: Recent findings: In addition ... ...

Abstract	Purpose of review: The aim of this report is to examine critical relationships between amino acid and formate metabolism with particular reference to the production of formate, and to review novel functions of formate. Recent findings: In addition to well established mechanisms in one-carbon metabolism, formate may play an important role in early pregnancy by preventing the onset of neural tube defects in sensitive strains of mice, including mice with deficiencies in MTHFD1L, the glycine cleavage system and the mitochondrial folate transporter. Markedly elevated, circulating levels of formate are found in late pregnancy, including in cord blood, as well as elevated levels of amino acid precursors. These are consistent with specific roles for formate in late pregnancy. Serine metabolism may reduce NADP to NADPH and permit the use of NADPH in reductive reactions. Novel, noncanonical functions of formate include high rates of formate production from serine in cells and in cancers. Summary: Novel, noncanonical functions of formate continue to be discovered. Integrating their functions with well established elements of one-carbon metabolism remains an important future objective.
MeSH term(s)	Amino Acid Oxidoreductases/metabolism ; Amino Acids/metabolism ; Animals ; Female ; Formates/metabolism ; Humans ; Mice ; Multienzyme Complexes/metabolism ; Pregnancy ; Serine/metabolism ; Transferases/metabolism
Chemical Substances	Amino Acids ; Formates ; Multienzyme Complexes ; glycine cleavage system ; formic acid (0YIW783RG1) ; Serine (452VLY9402) ; Amino Acid Oxidoreductases (EC 1.4.-) ; Transferases (EC 2.-)
Language	English
Publishing date	2019-11-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1460178-3
ISSN	1473-6519 ; 1363-1950
ISSN (online)	1473-6519
ISSN	1363-1950
DOI	10.1097/MCO.0000000000000611
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Article ; Online: The role of dietary creatine.

Brosnan, Margaret E / Brosnan, John T

Amino acids

2016 Volume 48, Issue 8, Page(s) 1785–1791

Abstract: The daily requirement of a 70-kg male for creatine is about 2 g; up to half of this may be obtained from a typical omnivorous diet, with the remainder being synthesized in the body Creatine is a carninutrient, which means that it is only available to ... ...

Abstract	The daily requirement of a 70-kg male for creatine is about 2 g; up to half of this may be obtained from a typical omnivorous diet, with the remainder being synthesized in the body Creatine is a carninutrient, which means that it is only available to adults via animal foodstuffs, principally skeletal muscle, or via supplements. Infants receive creatine in mother's milk or in milk-based formulas. Vegans and infants fed on soy-based formulas receive no dietary creatine. Plasma and muscle creatine levels are usually somewhat lower in vegetarians than in omnivores. Human intake of creatine was probably much higher in Paleolithic times than today; some groups with extreme diets, such as Greenland and Alaskan Inuit, ingest much more than is currently typical. Creatine is synthesized from three amino acids: arginine, glycine and methionine (as S-adenosylmethionine). Humans can synthesize sufficient creatine for normal function unless they have an inborn error in a creatine-synthetic enzyme or a problem with the supply of substrate amino acids. Carnivorous animals, such as lions and wolves, ingest much larger amounts of creatine than humans would. The gastrointestinal tract and the liver are exposed to dietary creatine in higher concentrations before it is assimilated by other tissues. In this regard, our observations that creatine supplementation can prevent hepatic steatosis (Deminice et al. J Nutr 141:1799-1804, 2011) in a rodent model may be a function of the route of dietary assimilation. Creatine supplementation has also been reported to improve the intestinal barrier function of the rodent suffering from inflammatory bowel disease.
Language	English
Publishing date	2016-08
Publishing country	Austria
Document type	Journal Article ; Review
ZDB-ID	1121341-3
ISSN	1438-2199 ; 0939-4451
ISSN (online)	1438-2199
ISSN	0939-4451
DOI	10.1007/s00726-016-2188-1
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Article ; Online: Formate: The Neglected Member of One-Carbon Metabolism.

Brosnan, Margaret E / Brosnan, John T

Annual review of nutrition

2016 Volume 36, Page(s) 369–388

Abstract: Formate, the only non-tetrahydrofolate (THF)-linked intermediate in one-carbon metabolism, is produced in mammals from a variety of metabolic sources. It occurs in serum of adults at a concentration of approximately 30 μM. Its principal function lies as ... ...

Abstract	Formate, the only non-tetrahydrofolate (THF)-linked intermediate in one-carbon metabolism, is produced in mammals from a variety of metabolic sources. It occurs in serum of adults at a concentration of approximately 30 μM. Its principal function lies as a source of one-carbon groups for the synthesis of 10-formyl-THF and other one-carbon intermediates; these are primarily used for purine synthesis, thymidylate synthesis, and the provision of methyl groups for synthetic, regulatory, and epigenetic methylation reactions. Although formate is largely produced in mitochondria, these functions mostly occur in the cytoplasm and nucleus. Formate plays a significant role in embryonic development, as evidenced by the effectiveness of formate in the pregnant dam's drinking water on the incidence of neural tube defects in some genetic models. High formate concentrations in fetal lambs may indicate a role in fetal development and suggest that extracellular formate may play a role in the interorgan distribution of one-carbon groups.
MeSH term(s)	Animals ; DNA Methylation ; Dietary Supplements ; Epigenesis, Genetic ; Female ; Fetal Development ; Formates/blood ; Formates/metabolism ; Formates/therapeutic use ; Humans ; Male ; Maternal Nutritional Physiological Phenomena ; Methylation ; Mitochondria/enzymology ; Mitochondria/metabolism ; Models, Biological ; NADP/metabolism ; Neural Tube Defects/blood ; Neural Tube Defects/metabolism ; Neural Tube Defects/prevention & control ; Pentose Phosphate Pathway ; Pregnancy ; Protein Processing, Post-Translational ; Purines/biosynthesis ; RNA Processing, Post-Transcriptional ; Thymidine Monophosphate/biosynthesis
Chemical Substances	Formates ; Purines ; formic acid (0YIW783RG1) ; Thymidine Monophosphate (365-07-1) ; NADP (53-59-8)
Language	English
Publishing date	2016-07-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	406980-8
ISSN	1545-4312 ; 0199-9885
ISSN (online)	1545-4312
ISSN	0199-9885
DOI	10.1146/annurev-nutr-071715-050738
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Article ; Online: Glutamate: a truly functional amino acid.

Brosnan, John T / Brosnan, Margaret E

Amino acids

2013 Volume 45, Issue 3, Page(s) 413–418

Abstract: Glutamate is one of the most abundant of the amino acids. In addition to its role in protein structure, it plays critical roles in nutrition, metabolism and signaling. Post-translational carboxylation of glutamyl residues increases their affinity for ... ...

Abstract	Glutamate is one of the most abundant of the amino acids. In addition to its role in protein structure, it plays critical roles in nutrition, metabolism and signaling. Post-translational carboxylation of glutamyl residues increases their affinity for calcium and plays a major role in hemostasis. Glutamate is of fundamental importance to amino acid metabolism, yet the great bulk of dietary glutamate is catabolyzed within the intestine. It is necessary for the synthesis of key molecules, such as glutathione and the polyglutamated folate cofactors. It plays a major role in signaling. Within the central nervous system, glutamate is the major excitatory neurotransmitter and its product, GABA, the major inhibitory neurotransmitter. Glutamate interaction with specific taste cells in the tongue is a major component of umami taste. The finding of glutamate receptors throughout the gastrointestinal tract has opened up a new vista in glutamate function. Glutamate is truly a functional amino acid.
MeSH term(s)	Animals ; Functional Food ; Glutamic Acid/chemistry ; Glutamic Acid/metabolism ; Hemostasis ; Humans ; Neurotransmitter Agents/metabolism
Chemical Substances	Neurotransmitter Agents ; Glutamic Acid (3KX376GY7L)
Language	English
Publishing date	2013-09
Publishing country	Austria
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1121341-3
ISSN	1438-2199 ; 0939-4451
ISSN (online)	1438-2199
ISSN	0939-4451
DOI	10.1007/s00726-012-1280-4
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Article ; Online: Plasma Formate Is Greater in Fetal and Neonatal Rats Compared with Their Mothers.

Brosnan, Margaret E / Tingley, Garrett / MacMillan, Luke / Harnett, Brian / Pongnopparat, Theerawat / Marshall, Jenika D / Brosnan, John T

The Journal of nutrition

2020 Volume 150, Issue 5, Page(s) 1068–1075

Abstract: Background: Formate can be incorporated into 10-formyl-tetrahydrofolate (10-formyl-THF), which is a substrate for purine synthesis, and after further reduction of the one-carbon group, may be used as a substrate for thymidylate synthesis and for ... ...

Abstract	Background: Formate can be incorporated into 10-formyl-tetrahydrofolate (10-formyl-THF), which is a substrate for purine synthesis, and after further reduction of the one-carbon group, may be used as a substrate for thymidylate synthesis and for homocysteine remethylation. Objective: We examined plasma formate concentrations and the expression of genes involved in the production and utilization of formate in fetal and neonatal rats and in pregnant and virgin female rats. Methods: In 1 experiment, plasma formate was measured by GC-MS in rats aged 1-56 d. In a second experiment, virgin female (adult) rats, 19-d pregnant rats (P) and their male and female fetuses (F), and 3-d-old (N) and 7-d-old (J) offspring had plasma and amniotic fluid analyzed for formate by GC-MS, mRNA abundance in liver and placenta by qPCR, and several plasma amino acids by HPLC. Results: The plasma formate concentration was significantly higher in fetuses at embryonic day 19 than in the mothers. It was also significantly higher in neonatal rats but slowly returned to adult concentrations by ∼3 wk. The abundance of mitochondrial monofunctional 10-formyl-tetrahydrofolate synthetase (Mthfd1l) mRNA was significantly higher in placenta (PP) and F liver than in liver of N or J. Expression of mitochondrial bifunctional NAD-dependent methylene-tetrahydrofolate dehydrogenase/methenyl-tetrahydrofolate cyclohydrolase (Mthfd2) was significantly enriched in PP and liver of P, intermediate in F liver, and much lower in liver of N and J, relative to PP. Serine hydroxymethyltransferase 2 (Shmt2), methylenetetrahydrofolate dehydrogenase 1 (Mthfd1), and glycine decarboxylase protein of the glycine cleavage system (Gldc) mRNA expression was significantly lower in PP compared with other groups. Cytoplasmic NAD(P)-dependent 10-formyl-tetrahydrofolate dehydrogenase (Aldh1/1) and mitochondrial NAD(P)-dependent 10-formyl-tetrahydrofolate dehydrogenase (Aldh1/2) , genes responsible for the catabolism of 10-formylTHF, were very weakly expressed in PP, low in livers of F and N, and reached the significantly higher adult levels in J. Serine, glycine, and methionine concentrations in plasma of F were significantly higher than in plasma of P. Conclusions: Formate metabolism is highly active in fetuses and in placenta of pregnant rats.
MeSH term(s)	Aging ; Animals ; Animals, Newborn ; Female ; Fetus ; Formates/blood ; Formates/chemistry ; Liver/chemistry ; Maternal-Fetal Exchange ; Mothers ; Placenta/chemistry ; Pregnancy ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Formates ; formic acid (0YIW783RG1)
Language	English
Publishing date	2020-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1093/jn/nxz329
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Article: Herbicide resistance in annual bluegrass on Tennessee golf courses

Brosnan, James T. / Vargas, Jose J. / Breeden, Gregory K. / Zobel, John M.

Crop, forage & turfgrass management. 2020, v. 6, no. 1

2020

Abstract: Research was conducted to determine the extent of herbicide resistance in annual bluegrass (Poa annua L.) randomly collected from Tennessee golf courses during 2018. Harvested plants were cultured for seed collection, with progeny screened for resistance ...

Abstract	Research was conducted to determine the extent of herbicide resistance in annual bluegrass (Poa annua L.) randomly collected from Tennessee golf courses during 2018. Harvested plants were cultured for seed collection, with progeny screened for resistance to glyphosate (Roundup Pro; 32 fl oz acre⁻¹), foramsulfuron (Revolver; 17.4 fl oz acre⁻¹), simazine (Princep 4FL; 2 qt acre⁻¹), or prodiamine (Barricade 65WG; 0.001 mM). In postemergence herbicide screens, annual bluegrass collections were grouped based on survival percentage: resistant (>30% survival), segregating for resistance (5–30% survival), or susceptible (<5% survival). For prodiamine, annual bluegrass collections were screened in hydroponics and deemed resistant when <20% of plants exhibited symptoms of herbicide treatment (e.g., club roots), whereas those with >90% of plants showing symptoms were deemed susceptible; the remainder were intermediate and classified as segregating for resistance. In total, 64% of the annual bluegrass collections had some degree of resistance to glyphosate. Similarly, 21% had some degree of resistance to foramsulfuron, while 58% of annual bluegrass collections had some degree of resistance to prodiamine. Only 3% of the annual bluegrass collections were susceptible to simazine, and 25% of those surviving treatment were resistant to glyphosate or foramsulfuron. Multiple resistance to glyphosate, foramsulfuron, and simazine was reported in 4% of the annual bluegrass collections. The results of this research highlight the need for more diversified weed management strategies to control annual bluegrass on Tennessee golf courses.
Keywords	Poa annua ; forage ; glyphosate ; glyphosate resistance ; hydroponics ; prodiamine ; progeny ; seed collecting ; simazine ; turf management ; weed control ; Tennessee
Language	English
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ISSN	2374-3832
DOI	10.1002/cft2.20050
Database	NAL-Catalogue (AGRICOLA)

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Article: The role of dietary creatine

Brosnan, Margaret E / John T. Brosnan

Amino acids. 2016 Aug., v. 48, no. 8

2016

Abstract: The daily requirement of a 70-kg male for creatine is about 2Â g; up to half of this may be obtained from a typical omnivorous diet, with the remainder being synthesized in the body Creatine is a carninutrient, which means that it is only available to ... ...

Abstract	The daily requirement of a 70-kg male for creatine is about 2Â g; up to half of this may be obtained from a typical omnivorous diet, with the remainder being synthesized in the body Creatine is a carninutrient, which means that it is only available to adults via animal foodstuffs, principally skeletal muscle, or via supplements. Infants receive creatine in motherâs milk or in milk-based formulas. Vegans and infants fed on soy-based formulas receive no dietary creatine. Plasma and muscle creatine levels are usually somewhat lower in vegetarians than in omnivores. Human intake of creatine was probably much higher in Paleolithic times than today; some groups with extreme diets, such as Greenland and Alaskan Inuit, ingest much more than is currently typical. Creatine is synthesized from three amino acids: arginine, glycine and methionine (as S-adenosylmethionine). Humans can synthesize sufficient creatine for normal function unless they have an inborn error in a creatine-synthetic enzyme or a problem with the supply of substrate amino acids. Carnivorous animals, such as lions and wolves, ingest much larger amounts of creatine than humans would. The gastrointestinal tract and the liver are exposed to dietary creatine in higher concentrations before it is assimilated by other tissues. In this regard, our observations that creatine supplementation can prevent hepatic steatosis (Deminice et al. J Nutr 141:1799â1804, 2011) in a rodent model may be a function of the route of dietary assimilation. Creatine supplementation has also been reported to improve the intestinal barrier function of the rodent suffering from inflammatory bowel disease.
Keywords	adults ; animal models ; arginine ; carnivores ; creatine ; fatty liver ; foods ; gastrointestinal system ; humans ; infants ; inflammatory bowel disease ; Inuit ; liver ; males ; milk ; omnivores ; rodents ; S-adenosylmethionine ; skeletal muscle ; vegan diet ; wolves ; Greenland
Language	English
Dates of publication	2016-08
Size	p. 1785-1791.
Publishing place	Springer Vienna
Document type	Article
Note	Review
ZDB-ID	1121341-3
ISSN	1438-2199 ; 0939-4451
ISSN (online)	1438-2199
ISSN	0939-4451
DOI	10.1007/s00726-016-2188-1
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Article ; Online: Amino acids and proteins important for all; from stem cells, to the critically ill patient and even general bone health.

Rooyackers, Olav / Brosnan, John T

Current opinion in clinical nutrition and metabolic care

2014 Volume 17, Issue 1, Page(s) 59–60

MeSH term(s)	Amino Acids/administration & dosage ; Bone and Bones/drug effects ; Bone and Bones/metabolism ; Critical Illness/therapy ; Dietary Proteins/administration & dosage ; Humans ; Stem Cells/drug effects ; Stem Cells/metabolism
Chemical Substances	Amino Acids ; Dietary Proteins
Language	English
Publishing date	2014-01
Publishing country	England
Document type	Introductory Journal Article
ZDB-ID	1460178-3
ISSN	1473-6519 ; 1363-1950
ISSN (online)	1473-6519
ISSN	1363-1950
DOI	10.1097/MCO.0000000000000021
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Article ; Online: Creatine metabolism and the urea cycle.

Brosnan, John T / Brosnan, Margaret E

Molecular genetics and metabolism

2010 Volume 100 Suppl 1, Page(s) S49–52

Abstract: Because creatine and creatine phosphate are irreversibly converted to creatinine, there is a continuous need for their replacement. This occurs by means of diet and de novo synthesis. Dietary creatine is provided in animal products and can amount to ... ...

Abstract	Because creatine and creatine phosphate are irreversibly converted to creatinine, there is a continuous need for their replacement. This occurs by means of diet and de novo synthesis. Dietary creatine is provided in animal products and can amount to about half of the required amount. Synthesis provides the remainder. Creatine synthesis is a major component of arginine metabolism, amounting to more than 20% of the dietary intake of this amino acid. Creatine metabolism is of importance to patients with urea cycle disorders in two ways, both related to arginine levels. In patients with arginase deficiency, markedly elevated arginine levels may result in higher concentrations of guanidinoacetate and higher rates of creatine synthesis. This is of concern because it is thought that elevated levels of guanidinoacetate may exert neurotoxic effects. In the case of the other urea cycle disorders, arginine levels are markedly decreased unless the patients are supplemented with this amino acid. Decreased levels of arginine may result in decreased rates of creatine synthesis. This may be compounded by the fact that such patients, maintained on low protein diets, will also have lower dietary creatine intakes. There is some evidence that this may decrease brain creatine levels which may contribute to the neurological symptoms exhibited by these patients. It is clear that patients with urea cycle disorders also have altered creatine metabolism. Whether this contributes in a significant way to their neurological symptoms remains an open question.
MeSH term(s)	Animals ; Creatine/biosynthesis ; Creatine/deficiency ; Creatine/metabolism ; Glycine/analogs & derivatives ; Glycine/metabolism ; Humans ; Kidney/metabolism ; Urea/metabolism ; Urea Cycle Disorders, Inborn/enzymology
Chemical Substances	Urea (8W8T17847W) ; glycocyamine (GO52O1A04E) ; Creatine (MU72812GK0) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2010
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1418518-0
ISSN	1096-7206 ; 1096-7192
ISSN (online)	1096-7206
ISSN	1096-7192
DOI	10.1016/j.ymgme.2010.02.020
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