2-Oxoglutarate a-ketoglutarate

Isocitrate dehydrogenase catalyzes the first of two decarboxylations and dehydrogenations in the cycle. Three different isocitrate dehydrogenases are present one specific for NAD+ and found only in mitochondria, the other two specific for NADP+ and found in mitochondria and cytoplasm. The NAD -specific enzyme is the primary enzyme with regard to TCA cycle operation. All three require Mg + or Mn +. The reaction yields a-ketoglutarate (2-oxoglutarate), NAD(P)H, and CO2 and involves enzyme-bound oxalosuccinate as an intermediate. 

In the same scheme, a representation of the action of tyrosine transaminase (EC 2.6.1.5) acting on tyrosine (Tyr, Y) is shown. This enzyme utilizes pyridoxal phosphate to remove toe amino group from tyrosine (Tyr, Y) and transfer it to a-ketoglutarate (2-oxoglutarate) with formation of glutamate (Glu, E) from the latter and 4-hydroxyphenylpyruvate from the former. Then, 4-hydroxyphenylpyruvate decarboxylase (EC 4.1.1.80), which appears to require thiamine diphosphate and... 

Oxoglutaric acid (2-oxopentane-l,5-dioic, a-ketoglutaric acid) [328-50-7] M 146.1, m 114 , 115-117 , (pK ,( see oxaloacetic acid above). Crystd repeatedly from Me2CO/ benzene, EtOAc or ethyl propionate. 

As examples, two enzymes that will be discussed again later in this chapter are alanine transaminase (alanine aminotransferase) and aspartate transaminase (aspartate aminotransferase). In both cases, the amino group is transferred to 2-oxoglutarate (also known as a-ketoglutarate), which is oxoacid, above, forming glutamate as amino acid2. For example, the alanine transaminase (ALT) reaction is ... 

The product is 2-oxoglutarate, sometimes referred to as a-oxoglutarate or a-ketoglutarate. Note specifically that we have just lost one of the carbon atoms. Oxaloacetate (a C4 compound) reacted with acetyl-CoA (C2) to give citrate (Cg), and this reaction... 

The first oxidative step now follows. Isocitrate dehydrogenase oxidizes the hydroxyl group of isocitrate into an 0x0 group. At the same time, a carboxyl group is released as CO2, and 2-oxoglutarate (also known as a-ketoglutarate) and NADH+H"" are formed. 

This enzyme [EC 2.6.1.39] catalyzes the reversible reaction of 2-aminoadipate with 2-oxoglutarate (or, a-ketoglutarate) to generate 2-oxoadipate and glutamate. The enzyme requires pyridoxal phosphate. 

This enzyme [EC 2.6.1.42], also referred to as transaminase B, catalyzes the reversible reaction of leucine with a-ketoglutarate (or, 2-oxoglutarate) to produce 4-methyl-2-oxopentanoate and glutamate. The pyridoxal-phosphate-dependent enzyme will also utilize isoleucine and valine as substrates. However, this enzyme is distinct from that of valine pyruvate aminotransferase [EC 2.6.1.66]. See also Leucine Aminotransferase... 

This enzyme [EC 2.6.1.29] catalyzes the reaction of an a,ft)-diamine with a-ketoglutarate (or, 2-oxoglutarate) to generate an [Pg.194]

This enzyme [EC 1.14.11.7], also known as procolla-gen proline, 2-oxoglutarate 3-dioxygenase, catalyzes the reaction of a prolyl residue in procoUagen with dioxygen and a-ketoglutarate (or, 2-oxoglutarate) to produce a irans-3-hydroxyprolyl residue in procollagen, succinate, and carbon dioxide. This reaction also requires iron ions and ascorbate. 

Step 4 is the production of succinyl-CoA from 2-oxoglutarate and coenzyme A (CoASH), catalyzed by the 2-oxoglutarate dehydrogenase complex (which is often called a-ketoglutarate... 

Figure 6.3. GABA shunt as an alternative to a-ketoglutarate dehydrogenase in the citric acid cycle. 2-Oxoglutarate dehydrogenase, EC 1.2.4.2 glutamate decarboxylase, EC 4.1.1.15 GABA aminotransferase, EC 2.6.1.19 and succinic semialdehyde dehydrogenase, ECl.2.1.16.

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