The gluconeogenesis is the formation of glucose from a non-glucose precursor including pyruvate, lactate, and amino acids.
Pyruvate and Lactate:
Pyruvate is the end product of glycolysis which can be further metabolized to either acetyl CoA or lactate. The conversion of pyruvate to these products depend on tissue-type, ATP status, and regulatory effector molecules. The conversion of pyruvate to acetyl CoA is an irreversible step that is catalyzed by enzyme pyruvate dehydrogenase that occurs mainly in oxidative tissues such as liver, cardiac muscle. In contrast, the conversion of pyruvate to lactate is reversible step catalyzed by lactate dehydrogenase that occurs mainly in non-oxidative tissues such as red blood cells. The lactate dehydrogenase is also present in skeletal muscle that converts pyruvate to lactate during vigorous exercise.
Figure 1: Fates of Pyruvate PDH- Pyruvate dehydrogenase, LDH- Lactate dehydrogenase
Pyruvate and Lactate formed in peripheral tissues shuttled into the liver for gluconeogenesis:
The lactate formed during anaerobic glycolysis can directly be shuttled into the liver. In the liver, the lactate dehydrogenase isoenzyme converts lactate and pyruvate. Alternately, the lactate formed during anaerobic glycolysis is reconverted into pyruvate and subsequently converted to alanine by enzyme alanine transaminase. The lactate or alanine diffuse into the bloodstream and taken up by the liver. In the liver, alanine is converted by liver alanine transaminase to convert into pyruvate.
Figure 2: Glucose-alanine cycle
Figure 3: Cori cycle in Erythrocytes
Amino acid
Glucogenic amino acids are the group of amino acids whose metabolic intermediates can enter into the gluconeogenic pathway and form glucose. The examples include alanine, aspartate, glutamate etc.
Pyruvate and Lactate:
Pyruvate is the end product of glycolysis which can be further metabolized to either acetyl CoA or lactate. The conversion of pyruvate to these products depend on tissue-type, ATP status, and regulatory effector molecules. The conversion of pyruvate to acetyl CoA is an irreversible step that is catalyzed by enzyme pyruvate dehydrogenase that occurs mainly in oxidative tissues such as liver, cardiac muscle. In contrast, the conversion of pyruvate to lactate is reversible step catalyzed by lactate dehydrogenase that occurs mainly in non-oxidative tissues such as red blood cells. The lactate dehydrogenase is also present in skeletal muscle that converts pyruvate to lactate during vigorous exercise.
Figure 1: Fates of Pyruvate PDH- Pyruvate dehydrogenase, LDH- Lactate dehydrogenase
Pyruvate and Lactate formed in peripheral tissues shuttled into the liver for gluconeogenesis:
The lactate formed during anaerobic glycolysis can directly be shuttled into the liver. In the liver, the lactate dehydrogenase isoenzyme converts lactate and pyruvate. Alternately, the lactate formed during anaerobic glycolysis is reconverted into pyruvate and subsequently converted to alanine by enzyme alanine transaminase. The lactate or alanine diffuse into the bloodstream and taken up by the liver. In the liver, alanine is converted by liver alanine transaminase to convert into pyruvate.
Figure 2: Glucose-alanine cycle
Figure 3: Cori cycle in Erythrocytes
Amino acid
Glucogenic amino acids are the group of amino acids whose metabolic intermediates can enter into the gluconeogenic pathway and form glucose. The examples include alanine, aspartate, glutamate etc.
Propionyl CoA
Propionyl CoA an intermediate of odd-chain fatty acids are also the precursor for the gluconeogenic pathway. Propionyl CoA is converted into methyl malonyl CoA by enzyme propionyl CoA carboxylase ( a biotin-containing enzyme). The methyl malonyl CoA is converted into succinyl CoA by enzyme methyl malonyl CoA mutase and the succinyl CoA enters TCA cycle to form oxaloacetate. The oxaloacetate thus formed enters the gluconeogenic pathway to form glucose.
Propionyl CoA an intermediate of odd-chain fatty acids are also the precursor for the gluconeogenic pathway. Propionyl CoA is converted into methyl malonyl CoA by enzyme propionyl CoA carboxylase ( a biotin-containing enzyme). The methyl malonyl CoA is converted into succinyl CoA by enzyme methyl malonyl CoA mutase and the succinyl CoA enters TCA cycle to form oxaloacetate. The oxaloacetate thus formed enters the gluconeogenic pathway to form glucose.