PathWhiz

Pathway Description

Purine Nucleotides Degradation II (aerobic)

Homo sapiens

Metabolic Pathway

Purine degradation to urate plays an important role in nitrogen metabolism in homo sapiens. This pathway starts with 3 similar branching pathways, all ending in the synthesis of xanthine. The first pathway starts with adenosine monophosphate (AMP) which is catalyzed by cytosolic 5'-nucleotidase 1A and 5'-nucleotidase to make adenosine. Adenosine is then catalyzed by adenosine deaminase with water and a proton to make inosine with a byproduct of ammonium. Inosine along with a phosphate is catalyzed by purine nucleoside phosphorylase to make hypoxathine with a byproduct of α-D-ribose-1-phosphate. This part of the pathway ends with hypoxathine being catalyzed by xanthine dehydrogenase to synthesize xanthine. The second part of the pathway starts with guanosine monophosphate (GMP) being catalyzed by cytosolic 5'-nucleotidase II and 5'-nucleotidase into guanosine. The same enzymes that catalyzed adenosine monophosphate to adenosine. Then guanosine is catalyzed by purine nucleoside phosphorylase and an added phosphate to make guanine with the byproduct of α-D-ribose-1-phosphate again. Guanine is then catalyzed by guanine deaminase and synthesizes xanthine with a byproduct of ammonium. The third part of this pathway starts with inosine monophosphate (IMP) along with NAD and water being catalyzed by inosine-5'-monophosphate dehydrogenase 1 and inosine-5'-monophosphate dehydrogenase 2 to make xanthosine 5-phosphate (XMP) with a byproduct of NADH and a proton. Both inosine-5'-monophosphate dehydrogenase 1 and 2 are inhibited by ppGpp or GMP, stopping this part of the pathway from occuring. XMP will be catalyzed by cytosolic 5'-nucleotidase II and 5'-nucleotidase to make xanthosine. Xanthosine with a phosphate is then catalyzed by purine nucleoside phosphorylase to make xanthine with a byproduct of α-D-ribose-1-phosphate. Once xanthine is synthesized in any of these three processes, it, with NAD and water, is catalyzed by xanthine dehydrogenase to synthesize urate or uric acid with a byproduct of NADH and a proton.

References

Purine Nucleotides Degradation II (aerobic) References

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Anzai N, Enomoto A, Endou H: Renal urate handling: clinical relevance of recent advances. Curr Rheumatol Rep. 2005 Jun;7(3):227-34. doi: 10.1007/s11926-996-0044-0.

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Kulikowska E, Kierdaszuk B, Shugar D: Xanthine, xanthosine and its nucleotides: solution structures of neutral and ionic forms, and relevance to substrate properties in various enzyme systems and metabolic pathways. Acta Biochim Pol. 2004;51(2):493-531. doi: 035001493.

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Nishino T, Okamoto K, Eger BT, Pai EF, Nishino T: Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J. 2008 Jul;275(13):3278-89. doi: 10.1111/j.1742-4658.2008.06489.x. Epub 2008 May 30.

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	2Fe-2S
	Adenosine
	Adenosine monophosphate
	Ammonium
	FAD
	Guanine
	Guanosine
	Guanosine 3',5'-bis(diphosphate)
	Guanosine monophosphate
	Hydrogen Ion
	Hypoxanthine
	Inosine
	Inosinic acid
	Magnesium
	Molybdopterin
	NAD
	NADH
	Phosphate
	Potassium
	Ribose 1-phosphate
	Uric acid
	Water
	Xanthine
	Xanthosine
	Xanthylic acid
	Zinc (II) ion

	Adenosine deaminase
	Cytosolic 5'-nucleotidase 1A
	Cytosolic purine 5'-nucleotidase
	Guanine deaminase
	Inosine-5'-monophosphate dehydrogenase 1
	Inosine-5'-monophosphate dehydrogenase 2
	Purine nucleoside phosphorylase
	Xanthine dehydrogenase/oxidase

		2Fe-2S
		Adenosine
		Adenosine monophosphate
		Ammonium
		FAD
		Guanine
		Guanosine
		Guanosine 3',5'-bis(diphosphate)
		Guanosine monophosphate
		Hydrogen Ion
		Hypoxanthine
		Inosine
		Inosinic acid
		Magnesium
		Molybdopterin
		NAD
		NADH
		Phosphate
		Potassium
		Ribose 1-phosphate
		Uric acid
		Water
		Xanthine
		Xanthosine
		Xanthylic acid
		Zinc (II) ion

		Adenosine deaminase
		Cytosolic 5'-nucleotidase 1A
		Cytosolic purine 5'-nucleotidase
		Guanine deaminase
		Inosine-5'-monophosphate dehydrogenase 1
		Inosine-5'-monophosphate dehydrogenase 2
		Purine nucleoside phosphorylase
		Xanthine dehydrogenase/oxidase