Chemistry Reference
In-Depth Information
phosphoenolpyruvate carboxykinase (PEPCK). In some species PEPCK is almost equally distributed between the
mitochondria and the cytosol, so that some PEP required for gluconeogenesis can be generated in the mito-
chondria and exported directly to the cytosol by a specific transport system (
Figure 5.15
)
. However, oxaloacetate
FIGURE 5.15
Transport of oxaloacetate and PEP from the mitochondria to the cytosol.
cannot cross the inner mitochondrial membrane directly, and must be converted to either aspartate by the action of
aspartate transaminase (Route 1) or to malate, by malate dehydrogenase (Route 2) (
Figure 5.15
). Route 2, often
called the malate shuttle, involves mitochondrial oxidation of NADH followed by cytosolic reduction of NAD
รพ
thereby allowing reducing equivalents as NADH to be transferred from the mitochondria to the cytosol, where
they are required for gluconeogenesis.
We already mentioned that the enzymes involved in the
-oxidation of fatty acids are located in the mito-
chondria. The source of two-carbon fragments for the biosynthesis of both fatty acids and isoprenoids like
cholesterol is acetyl CoA, which is generated by oxidative metabolism in the mitochondria. Acetyl CoA cannot
escape from the mitochondria, but it can be exported to the cyosol as citrate, where it is reconverted to oxaloacete
and acetyl CoA. Fatty acid (and cholesterol) biosynthesis takes place in the cyosol, and requires bicarbonate,
which is incorporated into acetyl CoA to form malonyl CoA by acetyl CoA carboxylase. The biosynthesis of fatty
acids, mostly the C
16
palmitate (Chapter 4), requires one molecule of acetyl CoA and seven molecules of malonyl
CoA. In animals, the seven enzymatic reactions which are required for fatty acid synthesis are present in a single
multifunctional protein complex, known as fatty acid synthase.
9
The synthase also contains an acyl-carrier protein
b
9. This is not the only example of Nature inventing the assembly line a long time before Henry Ford
e
both pyruvate dehydrogenase and
a
-ketoglutarate dehydrogenase mentioned earlier in the chapter are also multi-enzyme complexes.
