GLUCOSE-ALANINE CYCLE(CAHILL CYCLE)

BY

ADETORO, Kozzim Okikiade

12/55EH018

April, 2016

Outline Introduction

Alanine

Features of Alanine

Production of Alanine

The Glucose-Alanine Cycle

Conclusion

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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

Source: Hambly (2012)

Figure 1: Glucose-Alanine Cycle

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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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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

Figure 2: Plasma concentration of amino acids during the course of prolonged fasting.

Source: Felig et al. (1969)7

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

Source: Catris (2012) Source: Campbell (2012)

Figure 3a: Animal sources of alanine9

Figure 3b: Plant sources of alanine

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).

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Figure 4: Transamination of pyruvate

Source: Namrata (2012)11

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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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).

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Figure 5: The lactic (cori) cycle and the alanine cycle

Source: Murray et al. (2003)

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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).15

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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