7.4 Metabolic Conditions

Metabolic Conditions

You have learned about the pathways and the tissue metabolic capabilities, so now we’re going to apply that knowledge to three conditions: fasting, the Atkins diet, and the Ornish/Pritikin diet, as ways to illustrate how you can use this knowledge.

In fasting, we’re going to be considering what is happening metabolically during a prolonged period without food. This is a catabolic condition. The Atkins diet is a carbohydrate-restricted diet, so we are going to consider what happens metabolically when someone is eating a diet that essentially only contains protein and fat over an extended period of time. This is an anabolic condition. Finally, the Ornish/Pritikin diet is a very low-fat diet, so we’re going to consider what happens metabolically when someone is eating a diet that is essentially only carbohydrates and protein over an extended period of time. This is also an anabolic condition. For each of these conditions, we’re going to consider what is happening in the liver, muscle, adipose, and brain.

Now that you have an understanding of the glycemic response (Chapter 4) and macronutrient metabolism (Chapter 6), you should be able to understand the broader effects of insulin and glucagon that are summarized in the following tables. Knowing what hormone is elevated in the different conditions helps you to understand the metabolism that occurs in different conditions.

Table 7.41 Insulin’s effects on targets in tissues1,2

Table 7.42 Glucagon’s effects on targets in tissues2

Subsections:

• 7.41 Fasting
• 7.42 Atkins Diet
• 7.43 Ornish/Pritikin Diet

References & Links

• Gropper SS, Smith JL, Groff JL. (2008) Advanced Nutrition and Human Metabolism. Belmont, CA: Wadsworth Publishing.
• http://jpkc.gmu.cn/swhx/book/shyl/23.pdf

Fasting

In this condition a person has been fasting for an extended period of time (18 hours or longer). As a result, the person is in a catabolic state with low blood glucose levels, which leads the pancreas to secrete glucagon.

The liver will break down glycogen to secrete glucose for other tissues to use until its stores are exhausted. Amino acids and lactate from muscle will be used for gluconeogenesis to synthesize glucose that will also be secreted. Glycolysis will not be occurring to any great extent in an effort to spare glucose for use by other tissues. From the breakdown of amino acids, there will be an increase in the synthesis and secretion of urea from the liver to safely rid the body of ammonia from the amino acids. Fatty acids that are received from adipose tissue will be broken down to acetyl-CoA and used to synthesize ketone bodies that are secreted for use by tissues, such as the brain, that cannot directly use fatty acids as a fuel.

Muscle tissue will break down glycogen to glucose until glycogen stores are exhausted, and receive glucose from the liver that enters glycolysis, forming pyruvate. Glucose will be used for anaerobic (lactate) and aerobic (pyruvate) respiration. Pyruvate will enter the transition reaction to form acetyl-CoA. The acetyl-CoA will then enter the citric acid cycle, and NADH and FADH₂ produced will enter the electron transport chain to generate ATP. Once there isn’t enough glucose for the muscle to use, fatty acids taken up from adipose tissue, and from the breakdown of muscle triglyceride stores, will be broken down to create acetyl-CoA. The acetyl- CoA will then enter the citric acid cycle, and NADH and FADH₂ produced will enter the electron transport chain to generate ATP. Amino acids from protein breakdown and lactate (Cori Cycle) will be secreted to be used by the liver for gluconeogenesis.

The adipose tissue will break down triglycerides to fatty acids and release these for use by the muscle and the liver. It will not be taking up anything.

No References

• Atkins Diet

In this condition, assume a person just started into Phase I of the Atkins Diet and he/she has just consumed a meal of all protein and fat with no carbohydrates of any kind. As a result, this person is in an anabolic state, but blood glucose levels are low, meaning the pancreas will secrete glucagon.

Liver glycogen stores will be broken down to secrete glucose for other tissues. Glycolysis will not be occurring to any great extent, in order to spare glucose for other tissues. Using amino acids from digestion and lactate from muscle, gluconeogenesis will synthesize glucose that will also be secreted. From the breakdown of amino acids, there will be an increase in the synthesis and secretion of urea from the liver to safely rid the body of ammonia from the amino acids.

Amino acids will also be used for protein synthesis. Some triglycerides from chylomicron remnants taken up will be broken down to fatty acids. These will then be broken down to acetyl-CoA and used to synthesize ketone bodies that are secreted for tissues, such as the brain, that cannot directly use fatty acids as a fuel. Other triglycerides will be packaged into VLDL and secreted from the liver.

Muscle tissue is going to break down glycogen to glucose, and receive glucose from the liver that enters glycolysis, forming pyruvate. Glucose will be used for anaerobic (lactate) and aerobic (pyruvate) respiration. After glycogen is used up, most glucose will be used for anaerobic respiration to spare glucose. In aerobic respiration, pyruvate will enter the transition reaction to form acetyl-CoA. The acetyl-CoA will then enter the citric acid cycle, and NADH and FADH₂ produced will enter the electron transport chain to generate ATP. Once there is not enough glucose for the muscle to use, fatty acids from multiple sources will be broken down to acetyl-CoA. The acetyl-CoA will then enter the citric acid cycle, and NADH and FADH₂ produced will enter the electron transport chain to generate ATP. Amino acids taken up will be used for protein synthesis, and lactate will be secreted for the liver to use for gluconeogenesis (Cori cycle).

In adipose tissue, fatty acids are also going to be taken up. These fatty acids will be used to synthesize triglycerides for storage. With glucagon levels high in this condition, hormone- sensitive lipase (HSL) would be active. However, since this is an anabolic state, the net effect would be uptake of fatty acids after cleavage by lipoprotein lipase (LPL). The adipose tissue won’t be secreting anything under this condition.

No References

• Ornish/Pritikin Diet

In this condition, assume a person is on the Ornish/Pritikin Diet and just consumed a meal containing carbohydrates, with minimal but adequate amount of protein, and no fat. As a result, this person is in an anabolic state with high blood glucose levels, meaning the pancreas will secrete insulin.

The liver will take up glucose and synthesize glycogen until its stores are filled. After these stores are full, glucose can be broken down through glycolysis to pyruvate, then form acetyl- CoA in the transition reaction. Because we are in the fed or anabolic state, acetyl-CoA will be used for fatty acid synthesis, and the fatty acids will be used for triglyceride synthesis. However, evidence suggests that this de novo lipogenesis pathway does not occur to any great extent in humans1. These triglycerides will be packaged into VLDL and secreted from the liver. Amino acids will also be taken up and used for protein synthesis as needed. Because there is plenty of glucose, gluconeogenesis and ketone body synthesis will not be operating to any great extent.

Muscle tissue will take up glucose and synthesize glycogen until those stores are filled. Some glucose will go through glycolysis to produce pyruvate, then form acetyl-CoA in the transition reaction. The acetyl-CoA will enter the citric acid cycle, and NADH and FADH₂ produced will enter the electron transport chain to generate ATP. Fatty acids that are cleaved from VLDL, IDL, and LDL are also going to be taken up. These fatty acids will be used to synthesize triglycerides for storage. Whatever amino acids are taken up will be used for protein synthesis. The muscle will not be secreting anything in this condition.

The adipose tissue is going to take up glucose that will enter glycolysis, where pyruvate will be produced, then acetyl-CoA will be produced in the transition reaction. Because we are in the fed or anabolic state, the acetyl-CoA will be used for fatty acid synthesis, and the fatty acids will be used for triglyceride synthesis. However, evidence suggests that de novo lipogenesis does not occur to any great extent in humans1. Fatty acids that are going to be taken up and primarily used to synthesize triglycerides for storage. The adipose tissue won’t be secreting anything under this condition.

The brain will have plenty of glucose available for its use, so it is not going to have to use ketone bodies like it would during fasting and during prolonged Atkins diet consumption.

References & Links

• McDevitt RM, Bott SJ, Harding M, Coward WA, Bluck LJ, et al. (2001) De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women. Am J Clin Nutr 74(6): 737-746.