Gluconeogenesis

Gluconeogenesis est iter metabolicum, quod glucosum diversis ex substratis non carbohydratis format. Est iter ubiquitosum, quod in plantis, fungis, bacteriis allisque microorganismis inveniri queat. In vertebratis gluneogenesis imprimis in hepate^[1], minore in parte in corticis renum^[2] occurrit. Una cum itinere metabolico glycogenolysis, quae ieiunio ineunte gluconeogenesi citius rogatur, iter glucogenesis glycaemiam (i. e. magnitudinem glucosi in sanguine) augeri servat, ita hypoglycaemiam evitare. Plurimis animalibus gluconeogenesis observatur ieiunio, fame, diaeta minus carbohydrata, exercitatione intensa ineunte. Gubernatio itineris per factores et inhibitores et activatores, ut insulinum, glucagonum, cortisolum, et alias substantias fit, et aequilibrium inter se multitudinem formationis glucosi determinat^[3]. Insuper cerebrum valores glucosi sanguinei sensit, et per neurona parasympathica autonomica liberatio glucagoni stimulatur, ut ita formatio glucosi augeatur^[4].

Intineris substantia communis initium est pyruvatum. Gluconeogenesis, formatio glucosi ex pyruvato imprimis per gradus quinque describi potest:

Formatio oxaloacetati ope enzymi pyruvati carboxylasis (PC) et cofactoris vitamini B7 (biotini). Nota ut cyclus acidi citrici substratum oxaloacetati requirit, et oxaloacetatum praecipue in cellulis muscularibus in iter hoc transformatur ("anaplerosis")^[5]
Formatio phosphoenolopyruvati (PEP)
Formatio 2-phosphoglycerati ope enzymi enolasis, et formatio 3-phosphoglycerati ope phosphoglycerati mutasis, deinde 1,3- bisphosphoglycerati ope phosphoglycerati kinasis, postea glyceraldehydi 3-phosphati ope glyceraldehydi 3-phosphati dehydrogenasis, denique fructosi-1,6 bisphosphati ope aldolasis A
Gradus proximus velocitatem gluconeogensis terminat: dephosphorylatio ex fructoso-1,6 bisphosphato in fructosum-6 phosphatum ope enzymi fructosi-1,6 bisphosphatasis et cofactorum Mg²⁺ et Mn²⁺. Ex fructoso-6 phosphato oritur glucosum-6 phosphatum.
Hydrolysis glucosi-6 phosphati in glucosum, ope enzymi glucosi-6 phosphatasis

In diabete mellito resistentia contra insulinum occurrit ut restrictio glucogenesis commutata sit, ita hyperglycaemia apparere potest^[6]^[7].

Contextus

Organismus, organa eius, cellulae eorum, omnia constanter energia corporis universalis, quae molecula ATP est, requirunt, et ad istud ATP formandum pernecesse est glucosum. Fons externa glucosi est cibum, quod per duodenum et venam portam in hepatem et denique in sanguinem venit. In sanguine multitudo sanguinea glucosi ("saccharum sanguineum") constanter sustentanda est, quia tantum hoc aequilibrio cellulae corporis efficaciter ex sanguine glucosum extrahere possunt. Tamen talis influx glucosi externus in sanguinem restrictus temporum ciborum restat. Nimirum formatio glucosi ex fontibus internis fieri debet, quod ope certae catenae biochemicae, gluconeogenesis enim nominatae, perficitur. Glucosum ipsum in forma sua in corpore non conservari potest, sed per glycogenogenesem in glycogenum transfertur et sic in hepate conservatur. Inter cenas vero fontes ex glycogeno (carbohydratis), lactato, glycerolo (lipidis), aminoacidis (proteinis) terebrari solent. Quoad consumptionem lactati et aminoacidorum substantia communis est pyruvatum, quod initio per enzymum pyruvati decarboxylasis in oxaloacetatum transfertur. Aminoacida, imprimis alaninum, deinde serinum et alia gluconeogenesem quoque per oxaloacetatum, nunc scilicet cycli acidi citrici, intrant. Denique lipolysis, degradatio pinguis corporei, generat glycerolum, quod tarde catenae glycolysis addatur.

Locus intracellularis

Locus gluconeogenesis intra cellulas maiore in parte hepatis, hepatocytos, minore in parte cortice reni est.

Cursus

Substantiae praecursores

Itinieris substantiae praecursores sunt lactatum, alaninum, aminoacida in genere, et glycerolum. Lactatum glycolyse ineunte fabrefactum est^[8], alaninum et alia aminoacida de proteinis derivantur, et glycerolum de origine lipolysis est.

Ab lactato et alanino ad phosphoenolopyruvatum

Ante gluconeogenesem transformationem lactati, alanini et aliorum aminoacidorum in pyruvatum necesse est. Pyruvatum ipsum ope enzymi pyruvati carboxylasis in oxaloacetatum transformatur, deinde oxaloacetatum ope phosphoenolopyruvati carboxykinasis (PEPCK) in phosphoenolopyruvatum (PEP).

Ab aminoacidis trans cyclum citrici acidi ad phosphoenolopyruvatum

Etiam trans cyclum acidi citrici aminoacida in gluconeogenesem intrare queant. Cyclo acidi citrici ineunte etiam oxaloacetatum oritur, quod idemque in PEP transformatur.

Ab glycerolo ad fructosum 1,6-bisphosphatum

Glycerolum primum in glycerolum-3-phosphatum convertitur, deinde in dihydroxyacetonum-phosphatum, denum in fructosum 1,6-bisphospatum.

Ab phosphoenolopyruvato ad fructosum 1,6-bisphosphatum

Ab fructoso 1,6-bisphosphato ad glucosum

Formationis fructosi 1,6-bisphosponato duae substantiae, dihydroxyacetonum-phosphatum et glyceraldehyum-3-phosphatum, necesse sunt. Praeterea inter eas aequilibrium exstat. Formantur ex fructoso-1,6-bisphasphato primum fructosum-6-phosphatum, deinde glucosum-6-phosphatum, denique glucosum.

Morbi

Non raro alcoholismo functiones cellularum hepatis, hepatocytorum, deminutae sunt, ut post intoxicationem gluconeogenesis non satis glucosi generet. Valores restent parvae, hypoglycaemia cum confusione mentis observari potest.

Notae

↑ Exton J. H., Park C. R. (Iun 1967). "Control of gluconeogenesis in liver. I. General features of gluconeogenesis in the perfused livers of rats". The journal of biological chemistry 242 (11): 2622-36
↑ Gerich J. E. (Feb 2010). "Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications". Diabetic medicine 27 (2): 136-42 doi:10.1111/j.1464-5491.2009.02894.x
↑ Hatting M., Tavares C. D. J., Sharabi K., Rines A. K., Puigserver P. (Ian 2018). "Insulin regulation of gluconeogenesis". Annals of the New York Academy of Sciences 1411 (1): 21-35 doi:10.1111/nyas.13435
↑ Lamy C. M., Sanno H., Labouèbe G., Picard A., Magnan C., Chatton J.-Y., Thorens B. (Mar 2014). "Hypoglycemia-activated GLUT2 neurons of the nucleus tractus solitarius stimulate vagal activity and glucagon secretion". Cell metabolism 19 (3): 527-38 doi:10.1016/j.cmet.2014.02.003
↑ Anaplerosis, reactio anaplerotica, in biochemia significat: ad cyclum acidi citrici complendum
↑ Bogardus C., Lillioja S., Howard B. V., Reaven G., Mott D. (Oct 1984). "Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects". The journal of clinical investigation 74 (4): 1238-46 doi:10.1172/JCI111533
↑ Petersen M. C., Vatner D. F., Shulman G. I. (Oct 2017). "Regulation of hepatic glucose metabolism in health and disease". Nature reviews. Endocrinology 13 (10): 572-87 doi:10.1038/nrendo.2017.80
↑ Rabinowitz J. D., Enerbäck S. (Iul 2020). "Lactate: the ugly duckling of energy metabolism". Nature metabolism 2 (7): 566-71 doi:10.1038/s42255-020-0243-4

Plura legere si cupis

J. Brosnan, "Comments on metabolic needs for glucose and the role of gluconeogenesis", European Journal of Clinical Nutrition, 1999ː 107-111

Nexus interni

Lipolysis

Nexus externi

StatPearls de glucogenese (Anglice)

[1] Exton J. H., Park C. R. (Iun 1967). "Control of gluconeogenesis in liver. I. General features of gluconeogenesis in the perfused livers of rats". The journal of biological chemistry 242 (11): 2622-36

[2] Gerich J. E. (Feb 2010). "Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications". Diabetic medicine 27 (2): 136-42 doi:10.1111/j.1464-5491.2009.02894.x

[3] Hatting M., Tavares C. D. J., Sharabi K., Rines A. K., Puigserver P. (Ian 2018). "Insulin regulation of gluconeogenesis". Annals of the New York Academy of Sciences 1411 (1): 21-35 doi:10.1111/nyas.13435

[4] Lamy C. M., Sanno H., Labouèbe G., Picard A., Magnan C., Chatton J.-Y., Thorens B. (Mar 2014). "Hypoglycemia-activated GLUT2 neurons of the nucleus tractus solitarius stimulate vagal activity and glucagon secretion". Cell metabolism 19 (3): 527-38 doi:10.1016/j.cmet.2014.02.003

[5] Anaplerosis, reactio anaplerotica, in biochemia significat: ad cyclum acidi citrici complendum

[6] Bogardus C., Lillioja S., Howard B. V., Reaven G., Mott D. (Oct 1984). "Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects". The journal of clinical investigation 74 (4): 1238-46 doi:10.1172/JCI111533

[7] Petersen M. C., Vatner D. F., Shulman G. I. (Oct 2017). "Regulation of hepatic glucose metabolism in health and disease". Nature reviews. Endocrinology 13 (10): 572-87 doi:10.1038/nrendo.2017.80

[8] Rabinowitz J. D., Enerbäck S. (Iul 2020). "Lactate: the ugly duckling of energy metabolism". Nature metabolism 2 (7): 566-71 doi:10.1038/s42255-020-0243-4

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]