Metabolism 6 Flashcards
- Regulation of Metabolic Pathways:
- Occurs at rate-limiting steps
- Small changes greatly affect the flow of metabolites through the pathway.
- Regulation occurs at the first committed step of a pathway
- Not necessarily the first step of the pathway
- Regulatory enzymes catalyze irreversible reactions
- Different enzymes are used for synthetic and degradative pathways (reciprocal regulation)
- “Feedback regulation” is an important mechanism
- Catalytic activity
- Reversible allosteric control (___ control)
- Reversible covalent modification (phosphorylation and dephosphoryation)
- Hormonal regulation – ___ control (occurs in one or more tissues)
- Accessibility of substrates
- Synthetic/degradative pathways distinct
- Compartmentalization
- Regulation may vary in different organs
- *
Regulation of Metabolic Pathways:
Occurs at rate-limiting steps
Small changes greatly affect the flow of metabolites through the pathway.
Regulation occurs at the first committed step of a pathway
Not necessarily the first step of the pathway
Regulatory enzymes catalyze irreversible reactions
Different enzymes are used for synthetic and degradative pathways (reciprocal regulation)
“Feedback regulation” is an important mechanism
Catalytic activity
Reversible allosteric control (local control)
Reversible covalent modification (phosphorylation and dephosphoryation)
Hormonal regulation – global control (occurs in one or more tissues)
Accessibility of substrates
Synthetic/degradative pathways distinct
Compartmentalization
Regulation may vary in different organs
Regulatory molecules involved in glycolysis, citric acid cycle and gluconeogenesis
Glycolysis
CAC
Gluconeogenesis
Regulatory molecules involved in glycolysis, citric acid cycle and gluconeogenesis
Glycolysis
Hexokinase
Glucose 6 Phosphate
PFK1
AMP, F26BP
ATP, Citrate, H+
Pyruvate Kinase
ATP, Alanine
CAC
Pyruvate Dehydrogenase
Acetyl CoA, NADH, ATP
Isocitrate Dehydrogenase
ATP, NADH
AKG Dehydrogenase
Succinyl CoA, ATP, NADH
Gluconeogenesis
Pyruvate Carboxylase
Acetyl CoA
PEP Kinase
Phosphofructobisphosphatase
AMP, F26 BP
Key Junctions or Crossroads of metabolic pathways
___: Glycoylsis, PPP, Glycogen
____: Acetyl CoA for CAC and can act as backbone for aa. When you degrade aa, you form pyruvate
_____ is the center of it all.
Key Junctions or Crossroads of metabolic pathways
G6P: Glycoylsis, PPP, Glycogen
Pyruvate: Acetyl CoA for CAC and can act as backbone for aa. When you degrade aa, you form pyruvate
Acetyl CoA is the center of it all.
Eukaryotic cells compartmentalize pathways to help control regulation
Cytosol
____
____
____
Mitochondrial Matrix
___
____
___
____
Interplay of both compartments
____
____
Eukaryotic cells compartmentalize pathways to help control regulation
Cytosol
Glycolysis
PPP
Fa synthesis
Mitochondrial Matrix
CAC
Oxidatative Phosphorylation
B ox of fa
Ketone Body Formation
Interplay of both compartments
Gluconeogenesis
Urea Synthesis
Metabolic Adaptations
1st priority—_____
2nd priority—___ ____
Stored fuels (glycogen, TAGs and proteins) can meet needs for approximately __ ____
Carbohydrate reserves (glycogen) exhausted in ____
Brain needs continual supple of glucose.
Priority in starvation—glucose for____ (and survival of ____).
In muscle, ___ ____ can be converted to glucose but muscle needs to be ____
Muscle is the last resort
Metabolic Adaptations
1st priority—Glucose
2nd priority—Preserve muscle
Stored fuels (glycogen, TAGs and proteins) can meet needs for approximately 3 months.
Carbohydrate reserves (glycogen) exhausted in 1 day
Brain needs continual supple of glucose.
Priority in starvation—glucose for brain (and survival of RBC).
In muscle, amino acids can be converted to glucose but muscle needs to be preserved.
Muscle is the last resort
Brain
Depends on continual supply of glucose: Starvation: ketone bodies can replace glucose as major fuel source.
Ketone bodies are transportable equivalents of acetyl groups.
Fatty acids cannot be used as fuel because blood/brain barrier prevents entry.
Brain
Depends on continual supply of glucose: Starvation: ketone bodies can replace glucose as major fuel source.
Ketone bodies are transportable equivalents of acetyl groups.
Fatty acids cannot be used as fuel because blood/brain barrier prevents entry.
Muscle
Major fuel sources of skeletal: glucose, fatty acids, ketone bodies, amino acids
Large store of glycogen
Lack glucose 6-phosphatase so can’t export glucose
Contracting muscle—Rate of glycolysis exceeds rate of citric acid cycle
Pyruvate converted to lactate. Lactate transported to liver via blood.
Cori cycle—makes glucose for muscle
Preferred fuels used by the cardiac muscle are fatty acids, lactate and glucose. (lactate converted to pyruvate which is converted to acetylCoA which get oxidized to form ATP through oxidative phosphorylation)Prefers fa over glucose!
You get high amt of ATP when you oxidize fa
Muscle
Major fuel sources of skeletal: glucose, fatty acids, ketone bodies, amino acids
Large store of glycogen
Lack glucose 6-phosphatase so can’t export glucose
Contracting muscle—Rate of glycolysis exceeds rate of citric acid cycle
Pyruvate converted to lactate. Lactate transported to liver via blood.
Cori cycle—makes glucose for muscle
Preferred fuels used by the cardiac muscle are fatty acids, lactate and glucose. (lactate converted to pyruvate which is converted to acetylCoA which get oxidized to form ATP through oxidative phosphorylation)Prefers fa over glucose!
You get high amt of ATP when you oxidize fa
Adipose Tissue
Specialized tissue–Stores triacylglycerols (TAGs)
Esterification of fatty acids to form TAGs
Fatty acids released from TAGs by hormone-sensitive lipases
Glucose is needed for synthesis of TAGs
Glycerol 3-phosphate synthesized from glucose
Glucose level in adipose cell determines fate of fatty acid
Acetyl CoA can be synthesized from glucose and used to syn fa
Adipose Tissue
Specialized tissue–Stores triacylglycerols (TAGs)
Esterification of fatty acids to form TAGs
Fatty acids released from TAGs by hormone-sensitive lipases
Glucose is needed for synthesis of TAGs
Glycerol 3-phosphate synthesized from glucose
Glucose level in adipose cell determines fate of fatty acid
Acetyl CoA can be synthesized from glucose and used to syn fa
Liver
Essential for providing fuel for brain, muscle, etc.
Regulates blood levels of metabolites
Take up large amount of glucose
Glucokinase–enzyme responsible
Release glucose into blood when required
Regulation of lipid metabolism
When fuel abundant, synthesizes fatty acids and releases them as VLDL
Convert fatty acids to ketone bodies when Carbohydrates are low.
Liver
Essential for providing fuel for brain, muscle, etc.
Regulates blood levels of metabolites
Take up large amount of glucose
Glucokinase–enzyme responsible
Release glucose into blood when required
Regulation of lipid metabolism
When fuel abundant, synthesizes fatty acids and releases them as VLDL
Convert fatty acids to ketone bodies when Carbohydrates are low.
Regulation of glucose uptake into the liver
Glucokinase
Isozyme of hexokinase
Glucose is removed from the blood even when glucose levels are high in the blood.
Main function is 1st step in process converting excess glucose to glycogen
Hexokinase can be inhibited by G6P but Glucokinase cannot
Regulation of glucose uptake into the liver
Glucokinase
Isozyme of hexokinase
Glucose is removed from the blood even when glucose levels are high in the blood.
Main function is 1st step in process converting excess glucose to glycogen
Hexokinase can be inhibited by G6P but Glucokinase cannot
Regulation of fatty acid uptake in the liver
Formation of acyl carnitine is regulated
Carnitine acyl transferase (CAT) inhibited by malonyl CoA
Fatty acids do not enter mitochondria because CAT inhibited. No b-oxidation occurs.
[malonyl CoA] low then fatty acids are transported into mitochondria for b-oxidation
Regulation of fatty acid uptake in the liver
Formation of acyl carnitine is regulated
Carnitine acyl transferase (CAT) inhibited by malonyl CoA
Fatty acids do not enter mitochondria because CAT inhibited. No b-oxidation occurs.
[malonyl CoA] low then fatty acids are transported into mitochondria for b-oxidation
Three factors involved in the regulation of blood glucose levels
- Mobilization of glycogen & release of glucose by liver
- Release of fatty acids from adipose tissue
- Shift in fuel usage from glucose to fatty acids by muscle & liver
Result is maintenance of blood glucose at 80-120 mg/dl
Three factors involved in the regulation of blood glucose levels
- Mobilization of glycogen & release of glucose by liver
- Release of fatty acids from adipose tissue
- Shift in fuel usage from glucose to fatty acids by muscle & liver
Result is maintenance of blood glucose at 80-120 mg/dl
Metabolic adaptations under different physiologically relevant conditions
Exercise
Fed State
Fasting
Starvation
Diabetes
Metabolic adaptations under different physiologically relevant conditions
Exercise
Fed State
Fasting
Starvation
Diabetes
What are the metabolic demands during exercise?
Goal: Maintain energetic status (i.e. ATP/ADP ratio) of the cell
Result: Increase fuel utilization
Question: What are the mechanisms responsible for increasing fuel utilization?
What are the metabolic demands during exercise?
Goal: Maintain energetic status (i.e. ATP/ADP ratio) of the cell
Result: Increase fuel utilization
Question: What are the mechanisms responsible for increasing fuel utilization?
Fuel Utilization during exercise
Glygogen reserves broken down into G6P and converted to Glucose which will move thru blood to skeletal muscle where it will be reconverted in G6P, Pyruvate
Pyruvate will first go thru CAC, but as muscle contracts, rate of glycolysis will beat out CAC so you start to generate Pyruvate
Creatine Phosphate: when it is dephosphorylated, there is a large amount of E released
When you exhaust glycogen, liver will use non carb precursors to generate glucose
Muscle itself also has reserve of glycogen (it will use this first)
Then next best thing is fa which will undergo Box
Fuel Utilization during exercise
Glygogen reserves broken down into G6P and converted to Glucose which will move thru blood to skeletal muscle where it will be reconverted in G6P, Pyruvate
Pyruvate will first go thru CAC, but as muscle contracts, rate of glycolysis will beat out CAC so you start to generate Pyruvate
Creatine Phosphate: when it is dephosphorylated, there is a large amount of E released
When you exhaust glycogen, liver will use non carb precursors to generate glucose
Muscle itself also has reserve of glycogen (it will use this first)
Then next best thing is fa which will undergo Box
