Purine nucleotide cycle

Last updated
Phosphagen system (ATP-PCr) and purine nucleotide cycle (PNC) Purine Nucleotide Cycle.jpg
Phosphagen system (ATP-PCr) and purine nucleotide cycle (PNC)

The Purine Nucleotide Cycle is a metabolic pathway in protein metabolism requiring the amino acids aspartate and glutamate. The cycle is used to regulate the levels of adenine nucleotides, in which ammonia and fumarate are generated. [2] AMP converts into IMP and the byproduct ammonia. IMP converts to S-AMP (adenylosuccinate), which then converts to AMP and the byproduct fumarate. The fumarate goes on to produce ATP (energy) via oxidative phosphorylation as it enters the Krebs cycle and then the electron transport chain. Lowenstein first described this pathway and outlined its importance in processes including amino acid catabolism and regulation of flux through glycolysis and the Krebs cycle. [2] [3] [4]

Contents

AMP is produced after strenuous muscle contraction when the ATP reservoir is low (ADP > ATP) by the adenylate kinase (myokinase) reaction. [5] [6] AMP is also produced from adenine and adenosine directly; however, AMP can be produced through less direct metabolic pathways, such as de novo synthesis of IMP or through salvage pathways of guanine (a purine) and any of the purine nucleotides and nucleosides. IMP is synthesized de novo from glucose through the pentose phosphate pathway which produces ribose 5-P, which then converts to PRPP that with the amino acids glycine, glutamine, and aspartate (see Purine metabolism ) can be further converted into IMP. [7]

Reactions

The cycle comprises three enzyme-catalysed reactions. The first stage is the deamination of the purine nucleotide adenosine monophosphate (AMP) to form inosine monophosphate (IMP), catalysed by the enzyme AMP deaminase:

AMP + H2O + H+
 → IMP + NH3

The second stage is the formation of adenylosuccinate from IMP and the amino acid aspartate, which is coupled to the energetically favourable hydrolysis of GTP, and catalysed by the enzyme adenylosuccinate synthetase:

Aspartate + IMP + GTP → Adenylosuccinate + GDP + P
i

Finally, adenylosuccinate is cleaved by the enzyme adenylosuccinate lyase to release fumarate and regenerate the starting material of AMP:

Adenylosuccinate → AMP + Fumarate

A recent study showed that activation of HIF-1α allows cardiomyocytes to sustain mitochondrial membrane potential during anoxic stress by utilizing fumarate produced by adenylosuccinate lyase as an alternate terminal electron acceptor in place of oxygen. This mechanism should help provide protection in the ischemic heart. [8]

Occurrence

The purine nucleotide cycle occurs in the cytosol (intracellular fluid) of the sarcoplasm of skeletal muscle, and in the myocyte's cytosolic compartment of the cytoplasm of cardiac and smooth muscle. The cycle occurs when ATP reservoirs run low (ADP > ATP), such as strenuous exercise, fasting or starvation. [5] [9]

Proteins catabolize into amino acids, and amino acids are precursors for purines, nucleotides and nucleosides which are used in the purine nucleotide cycle. [7] The amino acid glutamate is used to neutralize the ammonia produced when AMP is converted into IMP. Another amino acid, aspartate, is used along with IMP to produce S-AMP in the cycle. Skeletal muscle contains amino acids for use in catabolism, known as the free amino acid pool; however, inadequate carbohydrate supply and/or strenuous exercise requires protein catabolism to sustain the free amino acids. [9]

When the phosphagen system (ATP-PCr) has been depleted of phosphocreatine (creatine phosphate), the purine nucleotide cycle also helps to sustain the myokinase reaction by reducing accumulation of AMP produced after muscle contraction in the below reaction. [6]

During muscle contraction:

H2O + ATP → H+
 + ADP + P
i ( Mg2+
 assisted, utilization of ATP for muscle contraction by ATPase)
H+
 + ADP + CP → ATP + Creatine (Mg2+
 assisted, catalyzed by creatine kinase, ATP is used again in the above reaction for continued muscle contraction)
2 ADP → ATP + AMP (catalyzed by adenylate kinase/myokinase when CP is depleted, ATP is again used for muscle contraction)

Muscle at rest:

ATP + Creatine → H+
 + ADP + CP (Mg2+
 assisted, catalyzed by creatine kinase)
ADP + P
i → ATP (during anaerobic glycolysis and oxidative phosphorylation)

AMP can dephosphorylate to adenosine and diffuse out of the cell; the purine nucleotide cycle may therefore also reduce the loss of adenosine from the cell since nucleosides permeate cell membranes, whereas nucleotides do not. [6]

Consequences

Aspartate and glutamate synthesis

Interaction between branched-chain amino acids and the purine nucleotide cycle in muscles Interaction between Branched-Chain Amino Acids and the Purine Nucleotide Cycle in muscles.png
Interaction between branched-chain amino acids and the purine nucleotide cycle in muscles

Fumarate, produced from the purine nucleotide cycle, is an intermediate of TCA cycle and enters the mitochondria by converting into malate and utilizing the malate shuttle where it is converted into oxaloacetic acid (OAA). During exercise, OAA either enters into TCA cycle or converts into aspartate in the mitochondria. [10]

As the purine nucleotide cycle produces ammonia (see below in ammonia synthesis), skeletal muscle needs to synthesize glutamate in a way that does not further increase ammonia, and as such the use of glutaminase to produce glutamate from glutamine would not be ideal. Also, plasma glutamine (released from the kidneys) requires active transport into the muscle cell (consuming ATP). [11] Consequently, during exercise when the ATP reservoir is low (ADP>ATP), glutamate is produced from branch-chained amino acids (BCAAs) and α-ketoglutarate, as well as from alanine and α-ketoglutarate. [12] Glutamate is then used to produce aspartate. The aspartate enters the purine nucleotide cycle, where it is used to convert IMP into S-AMP. [10] [13]

BCAAs + α-Ketoglutarate ⇌ Glutamate + Branch-chain keto acids (BCKAs) (catalyzed by Branched-chain aminotransferases (BCAT))
Alanine + α-Ketoglutarate ⇌ Pyruvate + Glutamate (catalyzed by alanine transaminase)
Oxaloacetic acid + Glutamate ⇌ α-Ketoglutarate + Aspartate (catalyzed by aspartate aminotransferase)

When skeletal muscle is at rest (ADP<ATP), the aspartate is no longer needed for the purine nucleotide cycle and can therefore be used with α-ketoglutarate to produce glutamate and oxaloacetic acid (the above reaction reversed).

α-Ketoglutarate + Aspartate ⇌ Oxaloacetic acid + Glutamate (catalyzed by aspartate aminotransferase)

Ammonia and glutamine synthesis

During exercise when the ATP reservoir is low (ADP>ATP), the purine nucleotide cycle produces ammonia (NH3) when it converts AMP into IMP. (With the exception of AMP deaminase deficiency, where ammonia is produced during exercise when adenosine, from AMP, is converted into inosine). During rest (ADP<ATP), ammonia is produced from the conversion of adenosine into inosine by adenosine deaminase.

AMP + H2O + H+
 → IMP + NH3 (catalyzed by AMP deaminase in skeletal muscle)
Adenosine + H2O → Inosine + NH3 (catalyzed by adenosine deaminase in skeletal muscle, blood, liver)

Ammonia is toxic, disrupts cell function, and permeates cell membranes. Ammonia becomes ammonium (NH+
4) depending on the pH of the cell or plasma. Ammonium is relatively non-toxic and does not readily permeate cell membranes. [14]

NH3 + H+
 ⇌ NH+
4

Ammonia (NH3) diffuses into the blood, circulating to the liver to be neutralized by the urea cycle. (N.b. urea is not the same as uric acid, though both are end products of the purine nucleotide cycle, from ammonia and nucleotides respectively.) When the skeletal muscles are at rest (ADP<ATP), ammonia (NH3) combines with glutamate to produce glutamine, which is an energy-consuming step, and the glutamine enters the blood. [15] [11]

Glutamate + NH3 + ATP → Glutamine + ADP + P
i (catalyzed by glutamine synthetase in resting skeletal muscle)

Excess glutamine is used by proximal tubule in the kidneys for ammoniagenesis, which may counteract any metabolic acidosis from anaerobic skeletal muscle activity. [15] In kidneys, glutamine is deaminated twice to form glutamate and then α-ketoglutarate. These NH3 molecules neutralise the organic acids (lactic acid and ketone bodies) produced in the muscles.

Glutamine + H2O → Glutamate + NH+
4 (catalyzed by glutaminase in the kidneys)

Pathology

Some metabolic myopathies involve the under- or over-utilization of the purine nucleotide cycle. Metabolic myopathies cause a low ATP reservoir in muscle cells (ADP > ATP), resulting in exercise-induced excessive AMP buildup in muscle, and subsequent exercise-induced hyperuricemia (myogenic hyperuricemia) through conversion of excessive AMP into uric acid by way of either AMP → adenosine or AMP → IMP.

During strenuous exercise, AMP is created through the use of the adenylate kinase (myokinase) reaction after the phosphagen system has been depleted of creatine phosphate and not enough ATP is being produced yet by other pathways (see above reaction in 'Occurrence' section). In those affected by metabolic myopathies, exercise that normally wouldn't be considered strenuous for healthy people, is however strenuous for them due to their low ATP reservoir in muscle cells. This results in regular use of the myokinase reaction for normal, everyday activities.

Besides the myokinase reaction, a high ATP consumption and low ATP reservoir also increases protein catabolism and salvage of IMP, which results in increased AMP and IMP. These two nucleotides can then enter the purine nucleotide cycle to produce fumarate which will then produce ATP by oxidative phosphorylation. If the purine nucleotide cycle is blocked (such as AMP deaminase deficiency) or if exercise is stopped and increased fumarate production is no longer needed, then the excess nucleotides will be converted into uric acid.

AMP deaminase deficiency (MADD)

AMP deaminase deficiency (formally known as myoadenylate deaminase deficiency or MADD) is a metabolic myopathy which results in excessive AMP buildup brought on by exercise. AMP deaminase is needed to convert AMP into IMP in the purine nucleotide cycle. Without this enzyme, the excessive AMP buildup is initially due to the adenylate kinase (myokinase) reaction which occurs after a muscle contraction. [16] However, AMP is also used to allosterically regulate the enzyme myophosphorylase (see Glycogen phosphorylase § Regulation ), so the initial buildup of AMP triggers the enzyme myophosphorylase to release muscle glycogen into glucose-1-P (glycogen→glucose-1-P), [17] which eventually depletes the muscle glycogen, which in turn triggers protein metabolism, which then produces even more AMP. In AMP deaminase deficiency, excess adenosine is converted into uric acid in the following reaction:

AMP → Adenosine → Inosine → Hypoxanthine → Xanthine → Uric Acid

Glycogenoses (GSDs)

Myogenic hyperuricemia, as a result of the purine nucleotide cycle running when ATP reservoirs in muscle cells are low (ADP > ATP), is a common pathophysiologic feature of glycogenoses such as GSD-III, GSD-V and GSD-VII, as they are metabolic myopathies which impair the ability of ATP (energy) production within muscle cells. In these metabolic myopathies, myogenic hyperuricemia is exercise-induced; inosine, hypoxanthine and uric acid increase in plasma after exercise and decrease over hours with rest. [18] Excess AMP (adenosine monophosphate) is converted into uric acid. [18]

AMP → IMP → Inosine → Hypoxanthine → Xanthine → Uric acid

Hyperammonemia is also seen post-exercise in McArdle disease (GSD-V) and phosphoglucomutase deficiency (PGM1-CDG, formerly GSD-XIV), due to the purine nucleotide cycle running when the ATP reservoir is low due to the glycolytic block. [19] [20] [21] [22] [23] [24]

AMP + H2O + H+
 → IMP + NH3

See also

Related Research Articles

<span class="mw-page-title-main">Citric acid cycle</span> Interconnected biochemical reactions releasing energy

The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of biochemical reactions to release the energy stored in nutrients through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. The chemical energy released is available under the form of ATP. The Krebs cycle is used by organisms that respire (as opposed to organisms that ferment) to generate energy, either by anaerobic respiration or aerobic respiration. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism. Even though it is branded as a "cycle", it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized.

<span class="mw-page-title-main">Nucleotide</span> Biological molecules constituting nucleic acids

Nucleotides are organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.

The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic.

<span class="mw-page-title-main">Adenosine monophosphate</span> Chemical compound

Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine. It is an ester of phosphoric acid and the nucleoside adenosine. As a substituent it takes the form of the prefix adenylyl-.

<span class="mw-page-title-main">Adenosine monophosphate deaminase deficiency type 1</span> Metabolic disorder leading to muscle dysfunction

Adenosine monophosphate deaminase deficiency type 1 or AMPD1, is a human metabolic disorder in which the body consistently lacks the enzyme AMP deaminase, in sufficient quantities. This may result in exercise intolerance, muscle pain and muscle cramping. The disease was formerly known as myoadenylate deaminase deficiency (MADD).

<span class="mw-page-title-main">Phosphoglucomutase</span> Metabolic enzyme

Phosphoglucomutase is an enzyme that transfers a phosphate group on an α-D-glucose monomer from the 1 to the 6 position in the forward direction or the 6 to the 1 position in the reverse direction.

<span class="mw-page-title-main">Glutamate dehydrogenase</span> Hexameric enzyme

Glutamate dehydrogenase is an enzyme observed in both prokaryotes and eukaryotic mitochondria. The aforementioned reaction also yields ammonia, which in eukaryotes is canonically processed as a substrate in the urea cycle. Typically, the α-ketoglutarate to glutamate reaction does not occur in mammals, as glutamate dehydrogenase equilibrium favours the production of ammonia and α-ketoglutarate. Glutamate dehydrogenase also has a very low affinity for ammonia, and therefore toxic levels of ammonia would have to be present in the body for the reverse reaction to proceed. However, in brain, the NAD+/NADH ratio in brain mitochondria encourages oxidative deamination. In bacteria, the ammonia is assimilated to amino acids via glutamate and aminotransferases. In plants, the enzyme can work in either direction depending on environment and stress. Transgenic plants expressing microbial GLDHs are improved in tolerance to herbicide, water deficit, and pathogen infections. They are more nutritionally valuable.

Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-catalyzed processes where chemical substances absorbed as nutrients serve as enzyme substrates, with conversion by the living organism either into simpler or more complex products. Examples of biosynthetic pathways include those for the production of amino acids, lipid membrane components, and nucleotides, but also for the production of all classes of biological macromolecules, and of acetyl-coenzyme A, adenosine triphosphate, nicotinamide adenine dinucleotide and other key intermediate and transactional molecules needed for metabolism. Thus, in biosynthesis, any of an array of compounds, from simple to complex, are converted into other compounds, and so it includes both the catabolism and anabolism of complex molecules. Biosynthetic processes are often represented via charts of metabolic pathways. A particular biosynthetic pathway may be located within a single cellular organelle, while others involve enzymes that are located across an array of cellular organelles and structures.

<span class="mw-page-title-main">Inosinic acid</span> Chemical compound

Inosinic acid or inosine monophosphate (IMP) is a nucleotide. Widely used as a flavor enhancer, it is typically obtained from chicken byproducts or other meat industry waste. Inosinic acid is important in metabolism. It is the ribonucleotide of hypoxanthine and the first nucleotide formed during the synthesis of purine nucleotides. It can also be formed by the deamination of adenosine monophosphate by AMP deaminase. It can be hydrolysed to inosine.

<span class="mw-page-title-main">Hitting the wall</span> Sudden fatigue during endurance sports

In endurance sports such as road cycling and long-distance running, hitting the wall or the bonk is a condition of sudden fatigue and loss of energy which is caused by the depletion of glycogen stores in the liver and muscles. Milder instances can be remedied by brief rest and the ingestion of food or drinks containing carbohydrates. Otherwise, it can be remedied by attaining second wind by either resting for approximately 10 minutes or by slowing down considerably and increasing speed slowly over a period of 10 minutes. Ten minutes is approximately the time that it takes for free fatty acids to sufficiently produce ATP in response to increased demand.

<span class="mw-page-title-main">AMP deaminase</span> Mammalian protein found in Homo sapiens

AMP deaminase 1 is an enzyme that in humans is encoded by the AMPD1 gene.

<span class="mw-page-title-main">Nucleic acid metabolism</span> Process

Nucleic acid metabolism is a collective term that refers to the variety of chemical reactions by which nucleic acids are either synthesized or degraded. Nucleic acids are polymers made up of a variety of monomers called nucleotides. Nucleotide synthesis is an anabolic mechanism generally involving the chemical reaction of phosphate, pentose sugar, and a nitrogenous base. Degradation of nucleic acids is a catabolic reaction and the resulting parts of the nucleotides or nucleobases can be salvaged to recreate new nucleotides. Both synthesis and degradation reactions require multiple enzymes to facilitate the event. Defects or deficiencies in these enzymes can lead to a variety of diseases.

<span class="mw-page-title-main">Amino acid synthesis</span> The set of biochemical processes by which amino acids are produced

Amino acid biosynthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids.

<span class="mw-page-title-main">Bioenergetic systems</span> Metabolic processes for energy production

Bioenergetic systems are metabolic processes that relate to the flow of energy in living organisms. Those processes convert energy into adenosine triphosphate (ATP), which is the form suitable for muscular activity. There are two main forms of synthesis of ATP: aerobic, which uses oxygen from the bloodstream, and anaerobic, which does not. Bioenergetics is the field of biology that studies bioenergetic systems.

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

<span class="mw-page-title-main">GMP synthase</span>

Guanosine monophosphate synthetase, also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate.

<span class="mw-page-title-main">GMP reductase</span> Class of enzymes

GMP reductase EC 1.7.1.7 is an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of GMP into IMP.

<span class="mw-page-title-main">Adenylosuccinate</span> Chemical compound

Adenylosuccinate is an intermediate in the interconversion of purine nucleotides inosine monophosphate (IMP) and adenosine monophosphate (AMP). The enzyme adenylosuccinate synthase carries out the reaction by the addition of aspartate to IMP and requires the input of energy from a phosphoanhydride bond in the form of guanosine triphosphate (GTP). GTP is used instead of adenosine triphosphate (ATP), so the reaction is not dependent on its products.

In enzymology, an adenosine-phosphate deaminase (EC 3.5.4.17) is an enzyme that catalyzes the chemical reaction

Fumarate lyase belongs to the lyase class of enzymes. These proteins use fumarate as a substrate. They have been shown to share a short conserved sequence around a methionine which is probably involved in the catalytic activity of this type of enzymes.

References

  1. ↑ Lewis AL, Guicherit OM, Datta SK, Hanten GR, Kellems RE (September 1996). "Structure and expression of the murine muscle adenylosuccinate synthetase gene". J Biol Chem. 271 (37): 22647–56. doi: 10.1074/jbc.271.37.22647 . PMID   8798436.
  2. 1 2 Lowenstein J.M. (1972). "Ammonia Production in Muscle and Other Tissues: the Purine Nucleotide Cycle". Physiological Reviews. 52 (2): 382–414. doi:10.1152/physrev.1972.52.2.382. PMID   4260884.
  3. ↑ Salway, J.G. (2004). Metabolism at a glance (3rd ed.). Malden, Mass.: Blackwell. ISBN   1-4051-0716-2. OCLC   53178315.
  4. ↑ Voet, Donald (2011). Biochemistry. Voet, Judith G. (4th ed.). Hoboken, NJ: Wiley. ISBN   978-0-470-57095-1. OCLC   690489261.
  5. 1 2 Valberg, Stephanie J. (2008-01-01), Kaneko, J. Jerry; Harvey, John W.; Bruss, Michael L. (eds.), "15. Skeletal Muscle Function", Clinical Biochemistry of Domestic Animals (6th ed.), San Diego: Academic Press, pp. 459–484, ISBN   978-0-12-370491-7 , retrieved 2023-10-10
  6. 1 2 3 Bhagavan, N.V.; Ha, Chung-Eun (2015). "19. Contractile Systems: Reaction and the Purine Nucleotide Cycle". Essentials of Medical Biochemistry (2nd ed.). Elsevier. ISBN   978-0-12-416687-5. OCLC   900438931.
  7. 1 2 "Purine Synthesis : Synthesis of Purine RiboNucleotides". 2022-04-29. Retrieved 2022-12-14.
  8. ↑ Sridharan V, Guichard J, Li CY, Muise-Helmericks R, Beeson CC, Wright GL (July 2008). "O(2)-sensing signal cascade: clamping of O(2) respiration, reduced ATP utilization, and inducible fumarate respiration". Am J Physiol Cell Physiol. 295 (1): C29–37. doi:10.1152/ajpcell.00466.2007. PMC   2493545 . PMID   18463229.
  9. 1 2 Baker JS, McCormick MC, Robergs RA (2010). "Interaction among Skeletal Muscle Metabolic Energy Systems during Intense Exercise". J Nutr Metab. 2010: 905612. doi: 10.1155/2010/905612 . PMC   3005844 . PMID   21188163.
  10. 1 2 Arinze, Ifeanyi J. (May 2005). "Facilitating understanding of the purine nucleotide cycle and the one-carbon pool: Part I: The purine nucleotide cycle". Biochemistry and Molecular Biology Education. 33 (3): 165–8. doi: 10.1002/bmb.2005.494033032469 . PMID   21638570. S2CID   35570434.
  11. 1 2 Cruzat, Vinicius; Macedo Rogero, Marcelo; Noel Keane, Kevin; Curi, Rui; Newsholme, Philip (2018-10-23). "Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation". Nutrients. 10 (11): 1564. doi: 10.3390/nu10111564 . PMC   6266414 . PMID   30360490.
  12. ↑ Wagenmakers, A. J. (1998). "Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism". Exercise and Sport Sciences Reviews. 26: 287–314. doi:10.1249/00003677-199800260-00013. ISSN   0091-6331. PMID   9696993. S2CID   21127358.
  13. ↑ Mann, Gagandeep; Mora, Stephen; Madu, Glory; Adegoke, Olasunkanmi A. J. (2021). "Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism". Frontiers in Physiology. 12: 702826. doi: 10.3389/fphys.2021.702826 . ISSN   1664-042X. PMC   8329528 . PMID   34354601.
  14. ↑ Wilson, David A., ed. (2012-01-01), "Ammonia", Clinical Veterinary Advisor, Saint Louis: W.B. Saunders, p. 905, doi:10.1016/b978-1-4160-9979-6.00355-x, ISBN   978-1-4160-9979-6 , retrieved 2023-03-22
  15. 1 2 Taneja, Vikas; Jasuja, Haneesh (November 2019). "Severe hyperammonemia from intense skeletal muscle activity: A rare case report and literature review". Medicine. 98 (47): e17981. doi:10.1097/MD.0000000000017981. ISSN   0025-7974. PMC   6882587 . PMID   31764807. S2CID   208276909.
  16. ↑ Sabina, Richard L.; Swain, Judith L.; Patten, Bernard M.; Ashizawa, Tetsuo; O'Brien, William E.; Holmes, Edward W. (1980-12-01). "Disruption of the Purine Nucleotide Cycle". Journal of Clinical Investigation. 66 (6): 1419–23. doi:10.1172/JCI109995. ISSN   0021-9738. PMC   371628 . PMID   7440723.
  17. ↑ Meyer, Francois; Heilmeyer, Ludwig M.G.; Haschke, Richard H.; Fischer, Edmond H. (December 1970). "Control of Phosphorylase Activity in a Muscle Glycogen Particle". Journal of Biological Chemistry. 245 (24): 6642–8. doi: 10.1016/s0021-9258(18)62582-7 . ISSN   0021-9258. PMID   4320610. S2CID   33852514.
  18. 1 2 Mineo, Ikuo; Kono, Norio; Hara, Naoko; Shimizu, Takao; Yamada, Yuya; Kawachi, Masanori; Kiyokawa, Hiroaki; Wang, Yan Lin; Tarui, Seiichiro (1987-07-09). "Myogenic Hyperuricemia". New England Journal of Medicine. 317 (2): 75–80. doi:10.1056/NEJM198707093170203. ISSN   0028-4793. PMID   3473284.
  19. ↑ Altassan, Ruqaiah; Radenkovic, Silvia; Edmondson, Andrew C.; Barone, Rita; Brasil, Sandra; Cechova, Anna; Coman, David; Donoghue, Sarah; Falkenstein, Kristina; Ferreira, Vanessa; Ferreira, Carlos; Fiumara, Agata; Francisco, Rita; Freeze, Hudson; Grunewald, Stephanie (January 2021). "International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1-CDG): Diagnosis, follow-up, and management". Journal of Inherited Metabolic Disease. 44 (1): 148–163. doi:10.1002/jimd.12286. PMC   7855268 . PMID   32681750.
  20. ↑ Stojkovic, Tanya; Vissing, John; Petit, François; Piraud, Monique; Orngreen, Mette C.; Andersen, Grete; Claeys, Kristl G.; Wary, Claire; Hogrel, Jean-Yves; Laforêt, Pascal (2009-07-23). "Muscle Glycogenosis Due to Phosphoglucomutase 1 Deficiency". New England Journal of Medicine. 361 (4): 425–7. doi: 10.1056/NEJMc0901158 . ISSN   0028-4793. PMID   19625727.
  21. ↑ Hogrel JY, Janssen JB, Ledoux I, Ollivier G, Béhin A, Stojkovic T, Eymard B, Voermans NC, Laforet P (October 2017). "The diagnostic value of hyperammonaemia induced by the non-ischaemic forearm exercise test". J Clin Pathol. 70 (10): 896–8. doi:10.1136/jclinpath-2017-204324. PMID   28400468.
  22. ↑ Rumpf, K. W.; Wagner, H.; Kaiser, H.; Meinck, H. M.; Goebel, H. H.; Scheler, F. (1981-12-01). "Increased ammonia production during forearm ischemic work test in McArdle's disease". Klinische Wochenschrift. 59 (23): 1319–20. doi:10.1007/BF01711182. ISSN   0023-2173. PMID   6947119. S2CID   25192276.
  23. ↑ Vissing, J.; MacLean, D. A.; Vissing, S. F.; Sander, M.; Saltin, B.; Haller, R. G. (2001-12-01). "The exercise metaboreflex is maintained in the absence of muscle acidosis: insights from muscle microdialysis in humans with McArdle's disease". The Journal of Physiology. 537 (Pt 2): 641–9. doi:10.1111/j.1469-7793.2001.00641.x. ISSN   0022-3751. PMC   2278977 . PMID   11731594.
  24. ↑ Wagenmakers, A. J.; Coakley, J. H.; Edwards, R. H. (May 1990). "Metabolism of branched-chain amino acids and ammonia during exercise: clues from McArdle's disease". International Journal of Sports Medicine. 11 Suppl 2: S101–113. doi:10.1055/s-2007-1024861. ISSN   0172-4622. PMID   2193889.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.