Integration of metabolism Flashcards
What is the metabolic profile of the brain?
Glucose
- It can use ketone bodies under certain conditions
What is the metabolic profile of the muscles?
1) Glucose
2) Fatty acids
3) Ketone bodies
What is the metabolic profile of the liver?
It provides fuel to the brain and muscles
- n the well-fed state, the liver is a glucose-user while during starvation it is a glucose-producer
What is the metabolic profile of the adipose tissue?
It provides fuel to the body
What is the metabolic profile of the RBC?
Only glucose (due to the fact that it lacks a mitochondria)
How is the metabolism regulated?
- Catabolism and anabolism cannot happen in the same place at the same time (when one is active the other is inhibited via phosphorylation), they are regulated via:
1) At the enzyme level (allosteric interaction and covalent modification and transcription)
2) Compartmentalization (the fact that catabolic and anabolic reactions occurs in different areas in the cell/organelles)
3) Specialization of the organs (glucose user/donor, depending on the state of the body starving/well-fed)
FYI regarding metabolism
1) ATP is the universal energy carrier
2) ATP is generated by the oxidation of the metabolic fuels (glucose, fatty acids or amino acids)
3) Reducing molecules (like NADH, NADPH and FADH) are the redox agents for the reductive biosynthesis
4) Biomolecules are constructed from a small set of building blocks
5) Biosynthetic and degradation pathways are distinct
What are the three main reactions by which different cycles cross-links?
1) Glucose-6-phosphate
2) Pyruvate
3) Acetyl-CoA
What is the different fates of G-6-P?
- Glucose is converted to G-6-P (found in liver and kidney) when it is transferred into the cell
1) G-6-P can be converted to pyruvate via the fructose-6-phosphate intermediate
2) G-6-P can be converted to G-1-P and then stored as glycogen
3) G-6-P can be converted to ribose-5-phosphate via the pentose phosphate pathway
-) G-6-P can be generated from glycogen stores or by gluconeogenesis
What are the different fates of pyruvate?
- Pyruvate is generated from G-6-P via glycolysis
1) Pyruvate can be reduced into lactate under anaerobic conditions (lactate must then be oxidized back into pyruvate)
2) Pyruvate can also be transaminated to form alanine (FYI: several AA are degraded into pyruvate)
3) Pyruvate can be carboxylated to form oxaloacetate in the matrix of the mitochondria (first step of gluconeogenesis, as Oxaloacetate can be converted to G-6-P)
4) Pyruvate can be oxidized into acetyl CoA via the pyruvate dehydrogenase complex
How is Acetyl-CoA produced?
1) Oxidative decarboxylation of pyruvate.
2) β-oxidation of fatty acids
3) Degradation of ketogenic amino acids
What are the different fates of Acetyl-CoA?
1) Completely oxidized into CO2 via the citric acid cycle
2) Converted to HMG-CoA, which in turn might get converted into ketone bodies or cholesterol (cholesterol synthesis)
3) It can be exported into the cytosol and converted into fatty acids (fatty acid synthesis)
4) It can also be used for the synthesis of ketone bodies (acetone, acetoacetate, B-hydroxybutyrate
What is the metabolic profile of the brain?
1) Glucose is the fuel of the brain
2) It consumes around 120g/day of glucose (60-70% of glucose utilization)
3) During starvation it utilizes ketone bodies
Describe the metabolic profile of the muscles
1) The major source of fuel is glucose during the well-fed state and fatty acids and ketone bodies in states of starvation
2) It stores 3/4 of all glycogen stores, and it is highly affected by the physical activity (where glycogen gets converted to G-1-P then G-6-P then undergoes glycolysis to produce ATP and thus energy)
3) Glucose is for burst of activity (producing lactate anaerobically), while phosphocreatine acts as a source of ATP during burst activity
What is the major source of fuel for the muscles in a person in the well-fed state?
Glucose
What is the major source of fuel for the brain in the state of starvation?
Ketone bodies
What is the major source of fuel for the brain in well-fed state?
Glucose
What is the source of fuel for the muscles in the starvation state?
1) Fatty acids
2) Ketone bodies
Describe the metabolic profile of the adipose tissue
1) Triacylglycerols are stored in the adipose tissue
2) Adipose tissue acts as an enormous reservoir for metabolic fuel
3) The synthesis of TAG needs glucose
4) Glucose levels determines whether or not fatty acids are released into the blood
- In a well-fed state –> high insulin –> activates the synthesis of triglycerides and thus FA synthesis
- In the fasting state: Glucagon is elevated and insulin is reduced, which activates hormone-sensitive lipase and breaks down the stored TAGs, glycerol from this will go to the liver to be used for gluconeogenesis while fatty acids will be distributed to be used as a source of energy all over the body ,and in the liver, they’re also converted to ketone bodies
What is the metabolic activity of the kidney?
1) The excrete urine & waste products
2) They filter the blood plasma 60 times per day
3) They reabsorb water and glucose
4) Serves as an important site for gluconeogenesis during starvation (G-6-P present)
Describe the metabolic activity of carbohydrates in the liver
- Carbohydrate metabolism in the liver is essential for providing the brain, muscles, and other organs with fuel (via glycogenolysis, gluconeogenesis and ketogenesis)
- Most of the compounds that are absorbed in the diet must pass through the liver
- It regulates the metabolites in the blood
Describe the metabolic activity of the liver towards fatty acids
- The liver cells synthesizes fatty acids, lipoprotein, cholesterol, ketone bodies and triacylglycerols
- Fatty acids will be converted to triglycerides, and it won’t be stored here it will be exported as VLDL, and if this pathway gets dysregulated what do we get? Fatty liver!
Describe the metabolic activity of the liver in regards to amino acids
1) The liver synthesizes proteins like the plasma proteins (All plasma proteins like albumin are synthesized in the liver from AA except immunoglobulins)
2) Amino acids are broken down in the liver via the urea cycle
3) Glucogenic amino acids are converted to pyruvate via gluconeogenesis
Describe the metabolic activity during a well-fed state (absorptive period or 2 hours from last meal)
- Insulin will signal the fed state:
1) Stimulates the storage of fuels (synthesis of TAGs in the adipose tissue and muscles)
2) Accelerates the uptake of blood glucose
3) Stimulates glycogen synthesis in the muscle and liver
4) Accelerates glycolysis in the liver
5) Increases the synthesis of fatty acids
6) Stimulates the synthesis of proteins
7) Suppresses gluconeogenesis by the liver
What happens to our metabolism during short period of starvation?
- Glucagon is the signal for the starved state, targeting the liver mainly, its functions include:
1) Mobilization of glycogen stores (breaking it down)
2) Inhibiting the synthesis of glycogen
3) Inhibiting the synthesis of fatty acids
4) It stimulates gluconeogenesis in the liver (releasing a large amount of glucose into the blood, maintaining the blood-glucose levels)
5) It promotes the muscles and liver to use fatty acids as fuel when the blood glucose levels drops
What is the first priority during a state of prolonged starvation?
Providing sufficient glucose to the brain and other tissues that depends on it
What is the secondary priority of the body during a state of prolonged starvation?
- Protein preservation by shifting from the utilization of glucose to the utilization of fatty acids and ketone bodies (mobilization of TAG in the adipose tissue + gluconeogenesis by the liver = the shifting of the muscle from glucose to fatty acids as a fuel)
What happens after 3 days of starvation?
The liver will form large amounts of ketone bodies, releasing it into the blood which will be utilized by the brain and heart as a source of fuel
What happens to the body after several week of starvation?
- Ketone bodies are the major fuel for the brain
- Once TAG stores are depleted, Protein degradation is stimulated leading to the death of the heart, liver and the function of the kidneys
Summarize the fate of glucose in the liver
Glucose is converted to G-6-P, and G6P can be used in:
1) Released to the blood as glucose
2) Stored as glycogen in the liver
3) Converted to acetyl-CoA:
- Acetyl-CoA can be converted to fatty acids and then phospholipids and triacylglycerols
- It can be converted to cholesterol
- It can enter the citric acid cycle and continue its way through the glycolysis and thus produce ATP
4) Converted to ribose-5-phosphate via the pentose phosphate pathway producing NADPH (acts as a reducing agent for cholesterol synthesis and fatty acid)
Summarize the different fates of fatty acids
Fatty acids can be converted to:
1) Liver lipids
2) Acetyl-CoA via b-oxidation (producing NADPH)
3) Free fatty acids in the blood
4) Transferred via the lipoprotein
5) The acetyl-CoA could then be converted to:
-Cholesterol (used for steroid synthesis and bile salt production)
- Integrated into the citric acid cycle
- Converted to ketone bodies in the blood
Summarize the different fates of amino acids in the liver
Amino acids can get:
1) Converted to liver proteins
2) Released as amino acids in the blood and plasma proteins
3) Converted to nucleotides, hormones, and porphyrins
4) Converted to pyruvate (which will produce NH3 which is released in urea
5) Pyruvate can have different fates:
- Converted to acetyl-CoA (which could undergo both gluconeogenesis and glycogenolysis, converted to fatty acids and then lipids)
- Pyruvate could get converted to glucose and then glycogen
6) Alanine an AA could also get converted to pyruvate directly
summarize what happens in prolonged starvation
1) Shifting from glucose to ketone bodies
2) Using TAG for energy if deplete then protein if depleted then death
