The FeedAbsorptive Cycle

in the Brain and

Skeletal Muscle
By Chance A. Bennett

 The Brain
Carbohydrate
Brain stores little glycogen
Relies almost entirely on circulating glucose
Oxygen used to oxidize glucose to carbon dioxide and water
Once inside neurons, metabolized to produce ATP
Cytoplasmic glucose undergoes glycolysis to produce
acetyl CoA
Turned into ATP
Skeletal Muscle
Depends on glucose during severe exercise
Oxidation of glucose increases during severe exercise
Fatty Acids (except in severe exercise)
Derived from fat metabolism
Beta Oxidation of free fatty acids
Major source of energy
Activated by exercise
Produces extra energy for brain tissue
Switches to fed state metabolism immediately after
digestion
Ketone Bodies as fuel source
Derived from fatty acid metabolism

The Brain

Energy Intensive Organ

Requires 25% of the bodys glucose utilization to function
properly
Catabolizes glucoses (Catabolism
Uses primarily glucose to function
Hypothalamus integration of energy and nutrient signals
Energy intake minus energy expenditure
Hormones secreted during digestion
Neurons to arcuate nucleus to higher order neurons
Targeted by regulatory hormones; the Big Three
Binding of hormones to their receptors cause
positive or negative response
2 types of neurons in arcuate nucleus
Alter their expression in order to secrete or
inhibit secretion of neuropeptides
Neurons secrete neuropeptide Y (NPY) and
agouti-related protein (AgRP)
Stimulate feeding
Paraventricular neurons (PVN)
Stimulate signal release that encourage
food intake

 Blood-Brain Barrier (BBB)

Gradient drives facilitated transport of glucose via GLUT
transporter
Reduced upon digestion to enable passage of key hormones and
metabolites
Tight junctions between vascular endothelial cells
Entry into the brain
Diffuse across membrane
Passive diffusion
Fatty Acids non saturable
Transport system in which fatty acids diffuse across
lipid membrane of the brain
In contrast, Saturable Transports/transportation:
Involves transportation of molecules using a
transport that is disabled once the transport
facilitates the maximum concentration,
with respect to conditions of homeostasis
Transporter Molecules

Metabolic Pathways

Brain
Glycolysis
Allosteric regulation via phosphofructokinase
Insulin (and Leptin) enter brain by means of saturable transporters
GLUT1 Transporter
Distributes glucose in the brain
Mediates glucose uptake from the extracellular flued
Diffuses through endothelium cells through tight gaps
Astrocytes end-feet absorb and transfer glucose to distant brain cells
Diffuse to other gap junction coupled astrocytes
Released at more distant sites from capillary
GLUT 3
Higher transport rate
Functions in Neuronal Glucose Uptake
Ensures neurons have sufficient glucose
Rapid neuronal uptake
Oligodendroglia
Microglia
Skeletal Muscle
Glycolysis (during exercise)
Increases to provide energy for muscle contraction
GLUT4 Transporter
Distributes glucose in the skeletal muscle

Glucose in
FeedAbsorptive
Cycle
in the Brain
and Skeletal
Muscle

Skeletal Muscle

Free Amino Acid Pool

Site of proteolysis
Release L-Alanine as a substrate for gluconeogenesis
Oxidation, transamination, metabolism within the muscle
BCAA- branched chain AA
Leucine
Isoleucine
Valine
Glutamate
Taken up during circulation during exercise
Dynamic role in intermediary metabolism
More sensitive to muscle contraction
Aspartate
Asparagine
Exercise
Skeletal muscles does receive sufficient oxygen supply to carry out
oxidation of glucose
Utilizes lactate produces by skin and blood
Short-term Exercise
Major impact on free amino acid pool
Alanine increases at moderate work intensities
Decrease in intramuscular glutamate
Prolonged Exercise
Glutamate remains stable
Alanine declines

TCA Cycle
Tricarboxylic acid (TCA) cycle
TCAI (TCA intermediates)
Series of eight reactions/intermediates
Molecules oxidized at high rates
Addition of dicarboxylates caused oxygen consumption from muscle tissue
Catalytic activity by promoting oxidation of other substrates present in tissue
For example:
Succinate; succinate dehydrogenase converts succinate into fumarate
Fumarate converted to succinate ; metabolized aerobically
Malate
Citrate
Mitochondria
Pyruvate oxidation
Oxidize acetyl group of acetyl CoA
Acetyl CoA
Derived from catabolism of carbs
Lipids
Certain AA
Generate reduced coenzymes
Utilized for re-synthesis of ATP through oxidative phosphorylation in electron transport
chain
NADH
FADH2

Well-Fed/Absorptive State

Well-fed state operates while food is being absorbed

from the intestine
Termed the absorptive state
The brain is dependent upon glucose catabolism for
its production of ATP
In the well-fed state, the liver utilizes glucose and
does not engage in gluconeogenesis
Thus, the Cori cycle is interrupted in the well-fed
state
In muscle, insulin promotes storage of glucose as
glycogen
Fed State Concentration of Metabolic Fuels
Glucose
5.5, 10-3 M
Ketone Bodies
0.01, 10-3 M
Fatty Acids
0.30, 10-3 M

Hormonal Regulation of Metabolism

Insulin
Function
Storage of glucose
Uptake of glucose
Storage of fatty acids
Inhibits breakdown of glucose
Satiety signal
The Pancreatic Beta Islet Cells
Secretes insulin in response to
carbohydrate consumption
(presence of glucose in the
blood)
Prevents glucose from over
accumulating in the blood
circulation
Communicates signals to the
brain and skeletal muscle

Immediately after a meal, blood glucose levels are high

Secretion of insulin from pancreatic cells.
Insulin is a signal of the fed-state.
Triggers metabolic events to eliminate dietary fuel for
storage as glycogen or TG.
Insulin stimulates glycogen synthesis in liver and muscle.
Insulin stimulates amino acid uptake and protein synthesis by
muscles
PYY 3-36
Passive diffusion across BBB into hypothalamus
Signal peptide in the gut
L-Cells of the distal small and large intestine
Signals satiety factor to brain
Inhibits gut motility and pancreatic secretion

Energy Sources During Exercise

Exercise rapidly depletes ATP
AMPK signal transduction helps maintain ATP SUPPLY
Stimulating oxidation of fatty acid oxidation
AMPK phosphorylation of metabolic enzyme acetyl-CoA carboxylase (ACC)
Inhibits enzymatic activity
ACC key control point in fatty acid oxidation
Skeletal Muscle
Brain
AMPK
Lactate is supplemental oxidative fuel
AMP-activated protein kinase
Elevated Lactate levels
Key regulator of energy balance on cellular level
Blood brain barrier
Stimulates energy producing catabolic processes
Selective permeability
Throttles back energy using anabolic processes
Entire brain flooded with lactate
AMPK Signaling
Lactate oxidized in the brain in amounts that rise
Increased glucose transport
with blood lactate level
Increased fatty acid oxidation (via beta
Glucose usually taken up by Brain is used the body and
oxidation)
lactate is supplemental source of fuel
Increased mitochondrial biogenesis

Conclusion
The structure of the Blood-Brain Barrier
regulates the metabolic activity that transpires
in the brain during the absorption state
Neurons facilitate or inhibit metabolism on a
cellular level
The brain is the origin of metabolism in
regards to the central nervous system
Amino acid metabolism varies, depending on
the type of exercise being conducted
The brain uses primarily glucose as energy
fuel source
Uses large portion of circulating glucose
In contrast, the skeletal muscle uses a variety
of macromolecules as energy fuel source,
depending on state of activity