3. INTRODUCTION
• Cahill cycle is a series of reactions in which amino groups from the muscle are
transported to the liver (Pankaja, 2011). It is a cycle where muscle protein is degraded
to provide more glucose to generate additional ATP for muscle contraction (Hambly,
2012).
• Cahill cycle is closely related with Cori’s cycle (Vasudevan et al., 2003).
• Muscle cannot export glucose because it lacks glucose-6-phosphatase. Nevertheless,
muscle serves the body as an energy reservoir (Voet and Voet, 2011).
• When muscles degrade amino acids for energy needs, the resulting nitrogen is
transaminated to pyruvate to form alanine. This alanine is shuttled to the liver where
the nitrogen enters the urea cycle and the pyruvate is used to make glucose (Figure 1)
(Wallace et al., 2002). 3
5. INTRODUCTION CONT’D
In muscle, pyruvate is converted to alanine, while in liver alanine is
converted to pyruvate which in turn is used to make glucose. When this
process occur simultaneously, it is referred to as the glucose-alanine cycle.
It occurs during extended periods of fasting, prolonged starvation, skeletal
muscle is degraded as an alternative source of energy thereby initiating this
cycle (Nabilah, 2014).
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6. ALANINE
Alanine is quantitatively the primary amino acid released by muscle and
extracted in prolonged fasted man. The hepatic capacity for conversion
of alanine to glucose exceeds that of all other amino acids (Felig, 1973).
The majority of plasma amino acids ultimately decrease in starvation,
the magnitude of this decline in both absolute and relative terms is
greatest for alanine exceeding all other amino acids. In addition, the rate
of decline in plasma alanine was most rapid during the 1st 5-10 days of
starvation (Figure 2) (Felig et al., 1969).
6
7. Figure 2: Plasma concentration of amino acids during the course of prolonged fasting.
Source: Felig et al. (1969) 7
8. FEATURES OF ALANINE
• Alanine is a nonessential and glucogenic amino acid (Nelson and Cox,
2005).
• Alanine is found in a wide variety of foods, but in particularly concentrated
in meats (Nabilah, 2014).
• One of the major amino acids emanating from muscle are alanine (destined
mainly for gluconeogenesis in liver and forming part of the glucose-alanine
cycle) (Murray, 2003).
• Alanine can be found in various sources (Figure 3a and 3b).
Animal sources: meat, seafood, dairy products, eggs, fish, gelatin (Catris, 2012).
Plant sources: beans, nuts, seeds, soybeans, brown rice, corn, legumes, whole grains
(Campbell, 2012).
8
9. Source: Catris (2012) Source: Campbell (2012)
Figure 3a: Animal sources of alanine
9
Figure 3b: Plant sources of alanine
10. PRODUCTION OF ALANINE
• Directly from protein degradation.
• Transamination of pyruvate by alanine transaminase (ALT)
[also referred to as serum glutamate-pyruvate transaminase]
(Figure 4) (Bryant, 2003).
10
12. THE GLUCOSE-ALANINE CYCLE
Reactions in skeletal muscle:
In muscle cells and other peripheral tissues, glycolysis produces pyruvate.
Pyruvate can be transaminated to alanine.
The transamination reaction requires an α-amino acid as donor of the amino group,
generating an α-keto acid in the process.
This reaction is catalyzed by alanine transaminase(ALT).
The alanine then enters the bloodstream
Alanine is transferred to the liver, the pyruvate formed is converted to glucose via
gluconeogenesis (Figure 5).
(Nabilah, 2014).
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13. Reactions in liver:
Liver receives alanine from muscle, accumulates plasma alanine, and reverses
the transamination.
Alanine is converted to pyruvate by deamination
Pyruvate is converted to glucose via gluconeogenesis.
The newly formed glucose can then enter the blood for delivery back into the
muscles (Figure 5).
(Nabilah, 2014).
13
14. Figure 5: The lactic (cori) cycle and the alanine cycle
Source: Murray et al. (2003)
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15. CAHILL CYCLE CONT’D
The Alanine pathway requires the presence of alanine aminotransferase
(ALT), which is restricted to tissues such as muscle, liver, and the
intestine. Therefore, this pathway is used instead of the Cori cycle only
when an aminotransferase is present and when there is a need to
transfer ammonia to the liver (Kung, 2014).
The ammonia can be converted to a less toxic waste product (Urea)
which can be excreted. Urea production occurs almost exclusively in
the liver by the enzymes of the Urea cycle and is the fate of most of the
ammonia channeled there (Nelson and Cox, 2005).
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16. CONCLUSION
Since there is a need for energy during starvation, the muscle protein
degrades leading to glucose-alanine cycle which involves the release of
nitrogen that can be used in the conversion of pyruvate to alanine.
The key feature of the cycle is that in one molecule of alanine,
peripheral tissue exports pyruvate and ammonia to the liver, where the
carbon skeleton is recycled for energy supply and most nitrogen
eliminated.
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