Chapter 22: Mammalian Fuel Metabolism: Integration and Regulation Flashcards
In this chapter, we summarize the specialized metabolism of different organs and the pathways that link them. We also examine the mechanisms by which extracellular hormones influence intracellular events. We conclude with a discussion of disruptions in mammalian fuel metabolism.
View google docs or pg 774 for summary of the major pathways of fuel metabolism in mammals
Proteins, glycogen, and triacylglycerols are built up from and broken down to smaller units: amino acids, glucose6-phosphate, and fatty acids. Oxidation of those fuels yields metabolic energy in the form of ATP. Pyruvate (a product of glucose and amino acid degradation) and acetyl-CoA (a product of glucose, amino acid, and fatty acid degradation) occupy central positions in mammalian fuel metabolism. Compounds that give rise to pyruvate, such as oxaloacetate, can be used for gluconeogenesis; acetyl-CoA can give rise to ketone bodies but not glucose. Not all the pathways shown here occur in all cells or occur simultaneously in a given cell.
The major metabolic pathways for glucose, fatty acids, and amino acids center on what two compounds?
acetyl-CoA and pyruvate
Pyruvate (a product of glucose and amino acid degradation) and acetyl-CoA (a product of glucose, amino acid, and fatty acid degradation)
Acetyl-CoA is the common degradation product of glucose, fatty acids, and ketogenic amino acids. Its acetyl group can be oxidized to CO 2 and H2 O via the citric acid cycle and oxidative phosphorylation or used to synthesize ketone bodies or fatty acids. Pyruvate is the product of glycolysis and the breakdown of glucogenic amino acids. It can be oxidatively decarboxylated to yield acetyl-CoA, thereby committing its atoms either to oxidation or to the biosynthesis of fatty acids. Alternatively, pyruvate can be carboxylated via the pyruvate carboxylase reaction to form oxaloacetate, which can either replenish citric acid cycle intermediates or give rise to glucose or certain amino acids.
What tissue can carry out all the reactions?
Liver
Nevertheless, about 60% of all metabolic enzymes, representing essential “housekeeping” functions, are expressed at some level in all tissues in the human body but liver is the most metabolically active tissue, followed by adipose tissue and skeletal muscle.
What 5 mammalian organs are we going over? How are they connected?
-brain, muscle, adipose tissue, liver, and kidney.
-connected via bloodstream
Metabolites flow between these organs in well-defined pathways in which flux varies with the nutritional state of the animal (Fig. 22-2). For example, immediately following a meal, glucose, amino acids, and fatty acids are directly available from the intestine. Later, when those fuels have been exhausted, the liver supplies other tissues with glucose and ketone bodies, whereas adipose tissue provides them with fatty acids. All these organs are connected via the bloodstream. In addition, the metabolic activities of numerous microorganisms contribute to mammalian fuel metabolism
Characteristics of brain tissue
- consumes 20% of O 2 taken up in resting state
- ATP needed for Na+ ,K+ -ATPase for maintaining membrane potential in neurons
- steady supply of glucose (or ketone bodies) from blood required
- dysfunction if blood glucose levels < 50 % of normal (~ 5 mM)
What is the brain’s primary fuel during usual conditions? How about during starvation or fast?
Under usual conditions, glucose is the brain’s primary fuel (although during an extended fast, the brain gradually switches to ketone bodies
Muscle’s major fuels are?
glucose (from glycogen), fatty acids, and ketone bodies.
Characteristics of the muscle
- stores glycogen (1 – 2% of muscle mass)
(stores glucose in the form of glycogen) - glycogen is not as efficient as triacylglycerides in storing energy. however, glycogen can be mobilized more rapidly than fat and because glucose can be metabolized anaerobically, fatty acids not
-In muscle, glycogen is converted to glucose-6-phosphate (G6P) for entry into glycolysis. Muscle cannot export glucose, however, because it lacks glucose-6phosphatase.
-Furthermore, although muscle can synthesize glycogen from glucose, it does not participate in gluconeogenesis because it lacks the required enzymatic machinery. Consequently, muscle carbohydrate metabolism serves only muscle.
- ATP used for muscle contraction (myosin)/Muscle contraction is driven by ATP hydrolysis (Section 7-2) and therefore requires either an aerobic or an anaerobic ATP regeneration system.
(Can work aerobically or anaerobically. Anaerobic needs glucose, not fat)
What is ATP used for in muscles? The body’s major source of ATP resupply? Under work, for immediate availability, ATP is regenerated from ?
ATP used for muscle contraction (myosin)/Muscle contraction is driven by ATP hydrolysis (Section 7-2) and therefore requires either an aerobic or an anaerobic ATP regeneration system.
Respiration (the citric acid cycle and oxidative phosphorylation)
Regenerated from phosphocreatine
ADP + phosphocreatine ↔ ATP + creatine
at rest, skeletal muscle uses how much of O2 taken up by body
Skeletal muscle at rest uses ∼30% of the O 2consumed by the human body. A muscle’s respiration rate may increase in response to a heavy workload by as much as 25-fold
- with Phosphocreatine supply exhausted, muscle shifts to ATP production via ?
glycolysis
The Heart Is Largely Anaerobic or Aerobic? What is its fuel?
Aerobic
Fatty acids are the resting heart’s fuel of choice, but during heavy work, the heart greatly increases its consumption of glucose, which is derived mostly from its relatively limited glycogen store.
heart muscle relies entirely on aerobic metabolism and is richly endowed with mitochondria; they occupy up to 40% of its cytoplasmic space.
- lactate build-up leads to?
pH decrease and muscle fatigue
Function of the adipose tissue? Where do the fatty acids come from?
The function of adipose tissue is to store and release fatty acids as needed for fuel as well as to secrete hormones involved in regulating metabolism.
- stores fat/triglycerides; releases it when needed
- 150 lb person – 30 lb fat (sufficient energy for ~ 3 months)
- fatty acids obtained from circulating lipoproteins in the blood
- glucose ↓, glycerol-3-phosphate ↓, triacylglycerol synthesis ↓, fatty acids released
3 fatty acids+glycerol form triglycerides
Liver functions
The liver maintains the proper levels of circulating fuels for use by the brain, muscles, and other tissues. It is uniquely situated to carry out this task because all the nutrients absorbed by the intestines except fatty acids are released into the portal vein, which drains directly into the liver.
* The liver makes all types of fuel available to other tissues.
One of the liver’s major functions is to act as a blood glucose “buffer.”
Fuel:
makes ketone bodies but does not use them s fuel
amino acids used as fuel
* when other fuels are scarce (muscle protein degradation)
main source of acetyl-CoA?
fatty acids
When the demand for metabolic fuels is high, fatty acids are degraded to acetyl-CoA
The liver also converts fatty acids to ketone bodies a
Glucokinase function?
Glucokinase Converts Blood Glucose to Glucose-6-Phosphate.
One of the liver’s major functions is to act as a blood glucose “buffer.”It does so by taking up and releasing glucose in response to hormones and to the concentration of glucose itself.
After a carbohydrate-containing meal, when the blood glucose concentration reaches ∼6 mM, the liver takes up glucose by converting it to G6P. This reaction is catalyzed by glucokinase, a liver isozyme of hexokinase (which is therefore also called hexokinase IV).
Glucokinase is also
* regulated by glucokinase regulatory protein
- inhibited in presence of F6P
- inhibition lifted by F1P
Compare Glucokinase and Hexokinase
The hexokinases in most cells obey Michaelis–Menten kinetics, have a high glucose affinity (K M < 0.1 mM), and are inhibited by their reaction product (G6P).
occurs in the liver
Glucokinase, in contrast, has much lower glucose affinity (reaching half-maximal velocity at ∼5 mM) and displays sigmoidal kinetics. Consequently, glucokinase activity increases rapidly with blood [glucose] over the normal physiological range (Fig. 22-4). Glucokinase, moreover, is not inhibited by physiological concentrations of G6P.
occurs in the muscle
