Question

Describe how expression of the two different isoforms of lactate dehydrogenase (LDH) allows the different organs of the body to cooperate under hypoxic states; that is, under low oxygen concentration. LDH isozymes must have 2 different conformations, where each conformation would bind O2 with different affinities. The two isozymes of LDH must have differing Km values, which would allow the enzyme with the low Km value to operate at low partial pressures of O2, and the enzyme with the higher KM value to operate at higher partial pressures of O2. The two isozymes of LDH must have differing kcat values, which would impact the rates of the reaction. The LDH isozymes must bind together to form large protein complex, which would impact the affinity for O2.

Answer 1

Okay, here is how the different isoforms of lactate dehydrogenase (LDH) allow cooperative functioning under hypoxia:

1. The LDH isozymes have different oxygen affinities due to differing Km values. One isozyme has a lower Km, allowing it to operate effectively at lower oxygen partial pressures. The other isozyme has a higher Km, allowing it to take over catalysis at higher oxygen levels. This allows continuous glycolysis across a range of oxygen conditions.

2. The isozymes have different kcat values, impacting the catalytic rate of the reaction at different oxygen levels. The isozyme with lower Km likely has a lower kcat, allowing slower conversion of lactate at low oxygen. The isozyme with higher Km likely has a higher kcat, enabling faster conversion of lactate when more oxygen is available. This helps match the flux through glycolysis to the oxygen supply.

3. The LDH isozymes can bind together to form larger protein complexes. This likely impacts their oxygen affinity, either increasing it ( allowing activity at even lower O2) or decreasing it (allowing activity at even higher O2). The formation of complexes provides additional flexibility and fine-tuning of enzyme activity based on oxygen levels.

4. With two isozymes, different organs can express the isozyme best suited for their typical oxygen microenvironment. For example, heart muscle might express the low Km isozyme, while liver might express the high Km isozyme. But under hypoxia, the isozymes can work together in a cooperative fashion by forming complexes or swapping subunits. This allows for a coordinated glycolytic response across organs under low oxygen conditions.

In summary, the key features that allow cooperative hypoxic functioning are: differing oxygen affinities (Km values), divergent catalytic rates (kcat values), the ability to form mixed complexes, and differential expression of isozymes tailored to organ-specific oxygen levels. These properties permit a graded and system-wide glycolytic response to decreasing oxygen supply.