7.4: Metabolic Conditions
- Page ID
- 21006
You have learned about the pathways and the tissue metabolic capabilities, so now you are going to apply that knowledge to four conditions: fed state, fasting, the Atkins diet, and the Ornish/Pritikin diet, as ways to illustrate how you can use this knowledge. In the fed state, we are going to be considering what is happening metabolically after consuming all 3 macronutrients. In fasting, we’re going to be considering what is happening metabolically during a prolonged period without food. 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 lipids over an extended period of time. 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. For each of these conditions, we’re going to consider what is happening in the liver, muscle, adipose, and brain.
Now that you should have an understanding of the glycemic response and macronutrient metabolism, 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.
| Effect | Tissue | Target |
|---|---|---|
| ↑ Glucose Uptake | Muscle, Adipose | ↑ GLUT4 |
| ↑ Glucose Uptake | Liver | ↑ Glucokinase |
| ↑ Glycogen Synthesis | Liver, Muscle | ↑ Glycogen Synthase |
| ↓ Glycogen Breakdown | Liver, Muscle | ↓ Glycogen Phosphorylase |
| ↑ Glycolysis,
↑ Transition Reaction |
Liver, Muscle | ↑ Phosphofructokinase-1
↑ Pyruvate Dehydrogenase Complex |
| ↑ Fatty Acid Synthesis | Liver | ↑ Fatty Acid Synthase |
| ↑ Triglyceride Synthesis | Adipose | ↑ Lipoprotein Lipase |
| Effect | Tissue | Target |
|---|---|---|
| ↑ Glycogen Breakdown | Liver | ↑ Glycogen Phosphorylase |
| ↓ Glycogen Synthesis | Liver | ↓ Glycogen Synthase |
| ↑ Gluconeogenesis | Liver | Multiple Enzymes |
| ↓ Glycolysis | Liver | ↓ Phosphofructokinase-1 |
| ↑ Ketone Body Synthesis | Liver | ↓ Acetyl-CoA Carboxylase |
| ↑ Triglyceride Breakdown | Adipose | ↑ Hormone-Sensitive Lipase |
The final subsection is a summary table that summarizes some pertinent details for these 4 conditions along with 100% protein, 100% carbohydrates, and 100% fat (triglyceride) diets.
Fed State
In this condition, assume a person just consumed a meal containing carbohydrates, protein and 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-\(\ce{CoA}\) will be used for ATP generation, but some acetyl-\(\ce{CoA}\) will also be used for fatty acid synthesis. Chylomicron remnants will also be taken up and fatty acids from them will also be used for triglyceride synthesis (along with fatty acids synthesized) to contribute to the pool of triglycerides found in the liver. Triglycerides from this pool 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.
The muscle will take up glucose and synthesize glycogen until those stores are filled. Some glucose will go through glycolysis to produce pyruvate, then form acetyl-\(\ce{CoA}\) in the transition reaction. The acetyl-\(\ce{CoA}\) will enter the citric acid cycle, and \(\ce{NADH}\) and \(\ce{FADH2}\) produced will enter the electron transport chain to generate ATP. Fatty acids that are cleaved from chylomicrons, 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 is going to take up glucose that will enter glycolysis, pyruvate will be produced, then acetyl-\(\ce{CoA}\) will be produced in the transition reaction. Because we are in the fed or anabolic state, the acetyl-\(\ce{CoA}\) will be used for fatty acid synthesis. Fatty acids will also be taken up from being cleaved from chylomicrons, VLDL, IDL, and LDL. These fatty acids from both synthesis and cleavage are primarily going to be used to synthesize triglycerides for storage. The adipose will not 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.
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 (minimal) and lactate (Cori cycle) from muscle will be used for gluconeogenesis to synthesize glucose that will also be secreted. Glycolysis will not be occurring to any great extent 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 the adipose will be broken down to acetyl-\(\ce{CoA}\). The acetyl-\(\ce{CoA}\) will then enter the citric acid cycle, and \(\ce{NADH}\) and \(\ce{FADH2}\) produced will enter the electron transport chain to generate ATP. The acetyl-\(\ce{CoA}\) will also be used to synthesize ketone bodies that are secreted for tissues, such as the brain, that cannot directly use fatty acids as a fuel.
The muscle will break down glycogen to glucose until glycogen stores are exhausted, and receive limited glucose from the liver that enters glycolysis, forming pyruvate. Most pyruvate will be converted to lactate to spare glucose (Cori cycle). Limited pyruvate will enter the transition reaction to form acetyl-\(\ce{CoA}\). Once there isn’t enough glucose for the muscle to use, fatty acids taken up from the adipose and from breakdown of muscle triglyceride stores will be broken down to acetyl-\(\ce{CoA}\). Acetyl-\(\ce{CoA}\) will then enter the citric acid cycle, and \(\ce{NADH}\) and \(\ce{FADH2}\) 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.
Given the limited glucose levels available, the brain will primarily be using ketone bodies as its fuel.
Atkins Diet
In this condition, assume a person has 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. 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 (Cori Cycle), gluconeogenesis will synthesize glucose (minimal) 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. Fatty acids will be cleaved from chylomicron remnants and broken down to acetyl-\(\ce{CoA}\) and used to synthesize ketone bodies that are secreted for tissues, such as the brain, that cannot directly use fatty acids as a fuel. Fatty acids from them will also be used for triglyceride synthesis to contribute to the pool of triglycerides found in the liver. Triglycerides from this pool will be packaged into VLDL and secreted from the liver.
The muscle will break down glycogen to glucose, and receive glucose from the liver that enters glycolysis, forming pyruvate. After glycogen is used up, most pyruvate produced by glycolysis is converted to lactate to spare glucose (minimal). Limited pyruvate will enter the transition reaction to form acetyl-\(\ce{CoA}\). The acetyl-\(\ce{CoA}\) will then enter the citric acid cycle, and \(\ce{NADH}\) and \(\ce{FADH2}\) produced will enter the electron transport chain to generate ATP. Once there is not enough glucose for the muscle to use, fatty acids will be cleaved from and taken up from chylomicrons, VLDL, IDL, and LDL and broken down to acetyl-\(\ce{CoA}\) in beta-oxidation. The acetyl-\(\ce{CoA}\) will then enter the citric acid cycle, and \(\ce{NADH}\) and \(\ce{FADH2}\) 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 the adipose, fatty acids that are cleaved from chylomicrons, VLDL, IDL, and LDL 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 would be active. However, since this is an anabolic state, the net effect would be uptake of fatty acids after cleavage by lipoprotein lipase. The adipose will not be secreting anything under this condition.
Given the limited glucose levels available, the brain will primarily be using ketone bodies as its fuel.
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 will be broken down through glycolysis to pyruvate, then form acetyl-\(\ce{CoA}\) in the transition reaction. Because we are in the fed or anabolic state, acetyl-\(\ce{CoA}\) will be used for fatty acid synthesis, and the fatty acids will be used for triglyceride synthesis. 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.
The muscle will take up glucose and synthesize glycogen until those stores are filled. Some glucose will go through glycolysis to produce pyruvate, then form acetyl-\(\ce{CoA}\) in the transition reaction. The acetyl-\(\ce{CoA}\) will enter the citric acid cycle, and \(\ce{NADH}\) and \(\ce{FADH2}\) produced will enter the electron transport chain to generate ATP. Fatty acids (minimal) 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 is going to take up glucose that will enter glycolysis, pyruvate will be produced, then acetyl-\(\ce{CoA}\) will be produced in the transition reaction. Because we are in the fed or anabolic state, the acetyl-\(\ce{CoA}\) will be used for fatty acid synthesis. Fatty acids will also be cleaved from VLDL, IDL, and LDL. Fatty acids from both sources are going to be taken up and primarily used to synthesize triglycerides for storage. The adipose will not 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.
Condition Summary
| Condition | Uptake | Secretion | Catabolic or Anabolic | Blood Glucose Concentration | Hormone Secreted | Cori Cycle | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Liver | Adipose | Muscle | Liver | Adipose | Muscle | |||||
| Fed State | Glucose, FA (CM Rem), AA | Glucose, FA | Glucose, FA, AA | VLDL | - | - | Anabolic | High | Insulin | - |
| Fasting | Lactate, AA, FA | - | FA, Glucose (minimal) | Urea, Ketone Bodies, Glucose (minimal), VLDL | FA | Lactate, AA | Catabolic | Low | Glucagon | + |
| Atkins | Lactate, AA, FA (CM Rem) | FA | AA, FA, Glucose (minimal) | Urea, Ketone Bodies, Glucose (minimal), VLDL | - | Lactate | Anabolic | Low | Glucagon | Low |
| Ornish | Glucose, AA | Glucose, FA | Glucose, AA, FA (minimal) | VLDL | - | - | Anabolic | High | Insulin | - |
| 100% protein | Lactate, AA | FA (minimal) | Glucose (minimal), AA, FA (minimal) | Urea, Ketone Bodies, Glucose, VLDL (minimal) | - | Lactate | Anabolic | Low | Glucagon | + |
| 100% carbohydrates | Glucose, AA | Glucose, FA | Glucose, FA | VLDL | - | AA | Anabolic | High | Insulin | - |
| 100% triglyceride | Lactate, AA, FA (CM Rem) | FA | Glucose (minimal), FA | Ketone Bodies, Glucose (minimal), VLDL | - | Lactate, AA | Anabolic | Low | Glucagon | Low |
| 100% Ethanol | ETOH, Lactate, AA, | FA | Glucose (minimal), FA | Ketone Bodies, Glucose (minimal), VLDL | - | Lactate, AA | Anabolic | Low | Glucagon | Low |
-, None; FA, Fatty acid; AA, Amino Acid; CM Rem, Chylomicron Remnant; VLDL, Very Low Density Lipoprotein
Summary Notes
- Adipose only takes up two things: glucose and fatty acid
- Glucose only when it is consumed (fed state, Ornish, 100% carbohydrates)
- Fatty acids in every condition except fasting
- Adipose only secretes fatty acids during fasting
- Muscle only takes up three things: glucose, fatty acid, amino acid
- Fatty acids in all; minimal in: Ornish and 100% protein
- Glucose in all; minimal in: 1) fasting; 2) no/low carbohydrate (Atkins, 100% protein, 100% triglyceride)
- Amino acids only when it is consumed in a meal (no other source)
- Muscle only secretes two things: amino acid and lactate
- Amino acids secreted when protein is not in diet (fasting, 100% carbohydrates, 100% triglyceride)
- Lactate secreted in: 1) fasting; 2) no/low carbohydrate diets (fasting, Atkins, 100% protein, 100% triglyceride, note these are the same conditions when minimal glucose is taken up)
- Liver takes up four things: glucose, fatty acids (from chylomicron remnants), amino acids, lactate
- Amino acid in all; source: food or from muscle
- Glucose only when it is consumed (fed state, Ornish, 100% carbohydrates)
- Fatty acids in: 1) fasting (adipose); 2) when it is consumed (fed state, Atkins, 100 triglyceride)
- Lactate (Cori cycle) in: 1) fasting; 2) no/low carbohydrate diets (Atkins, 100% protein, 100% triglyceride)
- Liver secretes four things: VLDL, glucose, urea, ketone bodies
- VLDL in all scenarios: 1) chylomicron remnants (triglycerides consumed) or 2) glucose ->acetyl-CoA -> FA
- Glucose is secreted in 100% protein and minimal in: 1) fasting; 2) Other no/low carbohydrate diets (Atkins, 100% triglycerides)
- Urea is secreted in 1) fasting; 2), high protein/carbohydrate restricted diets (Atkins, 100% protein)
- Ketone bodies in: 1) fasting, and 2) no/low carbohydrate diets (Atkins, 100% protein, 100% triglyceride)
References
- Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.
- jpkc.gmu.cn/swhx/book/shyl/23.pdf