Citrate

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A citrate can refer either to the conjugate base of citric acid, (C₃H₅O(COO)₃³⁻), or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.

Contents 1 Other citric acid ions 2 Acidity-Basicity 3 Buffering 4 Metabolism 4.1 TCA cycle 5 Fatty Acid Synthesis 5.1 Role in Glycolysis 6 References

[edit] Other citric acid ions

Since citric acid is a multifunctional acid, intermediate ions exist, hydrogen citrate ion, HC₆H₅O₇²⁻ and dihydrogen citrate ion, H₂C₆H₅O₇⁻. These may form salts as well, called acid salts.

[edit] Acidity-Basicity

Salts of the hydrogen citrate ions are weakly acidic, while salts of the citrate ion itself (with an inert cation such as sodium ion) are weakly basic.

[edit] Buffering

As a weak acid, citrate can be used as a component in buffer solutions, including the commonly used SSC 20X hybridization buffer^[1]. This buffer uses sodium citrate and sodium chloride to maintain a neutral 7.0 pH. Other buffers may use a mixture of sodium citrate and citric acid - canonical buffer tables compiled for biochemical studies^[2] describe solutions of citrate and acid for buffer pHs of between 3.0 and 6.2.

Citric acid can act as a mild chelating agent.

[edit] Metabolism

[edit] TCA cycle

Citrate is an intermediate in the TCA (Krebs) Cycle. After the pyruvate dehydrogenase complex forms acetyl CoA, from pyruvate and five cofactors (Thiamine pyrophosphate, lipoamide, FAD, NAD⁺, and CoA), citrate synthase catalyzes the condensation of oxaloacetate with Acetyl CoA to form citrate. Citrate continues in the TCA cycle via aconitase with the eventual regeneration of oxaloacetate, which can combine with another molecule of acetyl CoA and continue cycling.

[edit] Fatty Acid Synthesis

Citrate can also be transported out of the mitochondria and into the cytoplasm, then broken down into acetyl CoA for fatty acid synthesis. Citrate is a positive modulator of this conversion and allosterically regulates the enzyme acetyl-CoA carboxylase, which is the regulating enzyme in the conversion of Acetyl CoA into malonyl CoA (the commitment step in fatty acid synthesis). In short: Citrate is transported to the cytoplasm, converted to Acetyl CoA which is converted into Malonyl CoA by the Acetyl CoA carboxylase enzyme which is allosterically modulated by citrate.

See also TCA cycle

[edit] Role in Glycolysis

High concentrations of cytosolic citrate can inhibit phosphofructokinase, catalyst of one of the rate-limiting steps of glycolysis.

[edit] References

v • d • e Citric Acid Cycle Metabolic Pathway
			Oxaloacetate			Malate			Fumarate			Succinate			Succinyl-CoA
Acetyl-CoA				NADH + H+	NAD+			H2O		FADH2	FAD		CoA + ATP(GTP)	Pi + ADP(GDP)
	+	H2O														NADH + H+ + CO2
		CoA														NAD+
					H2O		H2O			NAD(P)+	NAD(P)H + H+			CO2
			Citrate			cis-Aconitate			Isocitrate			Oxalosuccinate			α-Ketoglutarate

v • d • e Amino acid metabolism metabolic intermediates K→acetyl-CoA lysine→ Saccharopine · Allysine · α-Aminoadipic acid · α-Aminoadipate · Glutaryl-CoA · Glutaconyl-CoA · Crotonyl-CoA · β-Hydroxybutyryl-CoA leucine→ α-Ketoisocaproic acid · Isovaleryl-CoA · 3-Methylcrotonyl-CoA · 3-Methylglutaconyl-CoA · HMG-CoA tryptophan→alanine→ N'-Formylkynurenine · Kynurenine · Anthranilic acid · 3-Hydroxykynurenine · 3-Hydroxyanthranilic acid · 2-Amino-3-carboxymuconic semialdehyde · 2-Aminomuconic semialdehyde · 2-Aminomuconic acid · Glutaryl-CoA G G→pyruvate→citrate glycine→serine→ 3-Phosphoglyceric acid glycine→creatine: Glycocyamine · Phosphocreatine · Creatinine G→glutamate→ α-ketoglutarate histidine→ Urocanic acid · Imidazol-4-one-5-propionic acid · Formiminoglutamic acid · Glutamate-1-semialdehyde proline→ 1-Pyrroline-5-carboxylic acid arginine→ Ornithine · Putrescine · Agmatine other cysteine+glutamate→glutathione: γ-Glutamylcysteine G→propionyl-CoA→ succinyl-CoA valine→ α-Ketoisovaleric acid · Isobutyryl-CoA · Methacrylyl-CoA · 3-Hydroxyisobutyryl-CoA · 3-Hydroxyisobutyric acid · 2-Methyl-3-oxopropanoic acid isoleucine→ 2,3-Dihydroxy-3-methylpentanoic acid · 2-Methylbutyryl-CoA · Tiglyl-CoA · 2-Methylacetoacetyl-CoA methionine→ generation of homocysteine: S-Adenosyl methionine · S-Adenosyl-L-homocysteine · Homocysteine conversion to cysteine: Cystathionine · alpha-Ketobutyric acid+Cysteine threonine→ α-Ketobutyric acid propionyl-CoA→ Methylmalonyl-CoA G→fumarate phenylalanine→tyrosine→ 4-Hydroxyphenylpyruvic acid · Homogentisic acid · 4-Maleylacetoacetate G→oxaloacetate see urea cycle Other Cysteine metabolism Cysteine sulfinic acid see also enzymes, disorders

v • d • e Antithrombotics (thrombolytics, anticoagulants and antiplatelet drugs) (B01) Antiplatelet drugs Glycoprotein IIb/IIIa inhibitors Abciximab • Eptifibatide • Tirofiban ADP receptor/P2Y12 inhibitors (Thienopyridines) Clopidogrel • Ticlopidine • Prasugrel Prostaglandin analogue (PGI2) Beraprost • Prostacyclin • Iloprost • Treprostinil COX inhibitors Acetylsalicylic acid/Aspirin # • Aloxiprin • Carbasalate calcium Other Ditazole • Cloricromen • Dipyridamole • Indobufen • Picotamide • Triflusal Anticoagulants Vitamin K antagonists (inhibit II, VII, IX, X) coumarins: Acenocoumarol • Coumatetralyl • Dicoumarol (Dicumarol) • Ethyl biscoumacetate • Phenprocoumon • Warfarin 1,3-Indandiones: Clorindione • Diphenadione • Phenindione other: Tioclomarol Factor Xa inhibitors (with some II inhibition) Heparin group/ glycosaminoglycans/ (bind antithrombin) low molecular weight heparin (Bemiparin, Certoparin, Dalteparin, Enoxaparin, Nadroparin, Parnaparin, Reviparin, Tinzaparin) oligosaccharides (Fondaparinux, Idraparinux) heparinoid (Danaparoid, Sulodexide, Dermatan sulfate) Direct Xa inhibitors xabans (Apixaban, Otamixaban, Rivaroxaban) Direct thrombin (II) inhibitors bivalent: Hirudin (Bivalirudin, Lepirudin, Desirudin) univalent: Argatroban • Dabigatran • Melagatran‡ • Ximelagatran‡ Other Defibrotide • Ramatroban • Antithrombin III • Protein C (Drotrecogin alfa) Thrombolytic drugs/ fibrinolytics plasminogen activators: TPA (Alteplase, Reteplase, Tenecteplase) • UPA (Urokinase, Saruplase) • Streptokinase # • Anistreplase • Monteplase other serine endopeptidases: Ancrod • Fibrinolysin Brinase Non-medicinal Citrate • EDTA • Oxalate #WHO-EM. ‡Withdrawn from market. CLINICAL TRIALS: †Phase III. §Never to phase III

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