I have read that red blood cells (RBCs) metabolize glucose. However they don't have any mitochondria because there is just so much hemoglobin that there is no room for mitochondria without expanding the cell.
So how is it possible for them to metabolize glucose if it is mainly O2, CO2, H2O, fatty acids (in cell membrane), and hemoglobin?
Answer
In humans (and all mammals), red blood cells lack mitochondria and therefore has no functional TCA cycle. They metabolize glucose mainly via glycolysis, forming lactate which is released from the cells; this yields 2 ATP for each glucose molecule, much less than complete oxidation (ca 30 ATP), but enough to support the red blood cells' energy needs.
There is some oxidation of glucose to CO2 in red blood cells though. This occurs mainly in the pentose phosphate pathway or "shunt", where 1 carbon of glucose is released as CO2, and the energy extracted is used to reduce NADP to NADPH, which functions as an antioxidant. The resulting 5-carbon sugars (pentoses) are then rearranged to a 3-carbon sugar (glyceraldehyde phosphate) which enter glycolysis again. Hence the term "shunt": 5/6 of the glucose carbon that enter actually comes back to glycolysis again.
By varying flux through the PPP, cells can balance the use of glucose for ATP (energy) or NADPH (antioxidant). Studies estimate that in human red blood cells, 10--30% of hexokinase flux is diverted through the PPP, and the remainder through upper glycolysis (see this and this article). This corresponds to 2--5% of glucose carbon released as CO2, and the remainder metabolized to lactate.
Note that the above apply to mammalian red blood cells. Red cells of other vertebrates, including birds and fish, retain both their nucleus and mitochondria, and their metabolism is different.
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