IDH3G
Isocitrate dehydrogenase  subunit gamma, mitochondrial is an enzyme that in humans is encoded by the IDH3G gene.
Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. NAD(+)-dependent isocitrate dehydrogenases catalyze the allosterically regulated rate-limiting step of the tricarboxylic acid cycle. Each isozyme is a heterotetramer that is composed of two alpha subunits, one beta subunit, and one gamma subunit. The protein encoded by this gene is the gamma subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. This gene is a candidate gene for periventricular heterotopia. Several alternatively spliced transcript variants of this gene have been described, but only some of their full length natures have been determined. 

# Structure
IDH3 is one of three isocitrate dehydrogenase isozymes, the other two being IDH1 and IDH2, and encoded by one of five isocitrate dehydrogenase genes, which are IDH1, IDH2, IDH3A, IDH3B, and IDH3G. The genes IDH3A, IDH3B, and IDH3G encode subunits of IDH3, which is a heterotetramer composed of two 37-kDa  subunits (IDH3), one 39-kDa  subunit (IDH3), and one 39-kDa  subunit (IDH3), each with distinct isoelectric points. Alignment of their amino acid sequences reveals ~40% identity between IDH3 and IDH3, ~42% identity between IDH3 and IDH3, and an even closer identity of 53% between IDH3 and IDH3, for an overall 34% identity and 23% similarity across all three subunit types. Notably, Arg88 in IDH3 is essential for IDH3 catalytic activity, whereas the equivalent Arg99 in IDH3 and Arg97 in IDH3 are largely involved in the enzyme's allosteric regulation by ADP and NAD. Thus, it is possible that these subunits arose from gene duplication of a common ancestral gene, and the original catalytic Arg residue were adapted to allosteric functions in the - and -subunits. Likewise, Asp181 in IDH3 is essential for catalysis, while the equivalent Asp192 in IDH3 and Asp190 in IDH3 enhance NAD- and Mn2+-binding. Since the oxidative decarboxylation catalyzed by IDH3 requires binding of NAD, Mn2+, and the substrate isocitrate, all three subunits participate in the catalytic reaction. Moreover, studies of the enzyme in pig heart reveal that the  and  dimers constitute two binding sites for each of its ligands, including isocitrate, Mn2+, and NAD, in one IDH3 tetramer.

# Function
As an isocitrate dehydrogenase, IDH3 catalyzes the reversible oxidative decarboxylation of isocitrate to yield -ketoglutarate (-KG) and CO2 as part of the TCA cycle in glucose metabolism. This step also allows for the concomitant reduction of NAD+ to NADH, which is then used to generate ATP through the electron transport chain. Notably, IDH3 relies on NAD+ as its electron acceptor, as opposed to NADP+ like IDH1 and IDH2. IDH3 activity is regulated by the energy needs of the cell: when the cell requires energy, IDH3 is activated by ADP; and when energy is no longer required, IDH3 is inhibited by ATP and NADH. This allosteric regulation allows IDH3 to function as a rate-limiting step in the TCA cycle. Within cells, IDH3 and its subunits have been observed to localize to the mitochondria.

# Clinical Significance
The IDH3G gene may be involved in drug resistance in gastric cancer.

# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. 
-  The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}