CEREBRAL METABOLISM AND BLOOD FLOW
I. CEREBRAL METABOLISM
The brain is metabolically one of the most active of all organs in the body.
The brain does not store excess energy and derives almost all of its energy needs from
aerobic oxidation of glucose.
It requires a continuous supply of glucose and oxygen to meet its energy requirements.
Most of the brain’s energy consumption is used for active transport of ions to sustain and
restore the membrane potentials discharged during the process of excitation and
conduction.
When blood flow to the brain stops and absence of oxygen and blood occurs, a loss of
consciousness results in 5-10 seconds.
If the blood flow is not resumed within several minutes, there is permanent brain damage.
During crises, such as cardiac arrest, damage to the brain occurs earliest and is most
decisive in determining the degree of recovery.
The absence of glucose is equally destructive, but the time course resulting in irreversible
damage from hypoglycemia is longer because other substrates can be used.
Glucose metabolism is the major energy source for the brain.
Glucose from the blood enters the brain with help of GLUT-1 transport protein.
Once inside a brain cell, it enters the glycolytic pathway, where it is converted to
pyruvate and then metabolized through the Krebs cycle to generate ATP.
A fraction of ATP molecules is used to generate high energy phosphocreatine molecules.
Under certain conditions, aerobic metabolism of phosphocreatine to maintain normal
function. When brain failure occurs, there is loss of phosphocreatine initially, followed
by ATP depletion, which generally signals severe damage to the brain.
Hypoglycemia, which can result from excessive insulin is associated with changes in
mental state. These changes can be rapidly reversed by glucose administration as during
starvation, the brain can use “ketone bodies” in place of glucose as substrates.
Ketone Bodies, Acetoacetate and D-β-Hydroxybutyrate are formed from catabolism of
fatty acids by the liver.
The ketone bodies are metabolized to generate Acyl-CoA which enters the Tricarboxylic
Acid Cycle (TCA) at a sufficient rate to meet the metabolic demand of the brain.
1
,II. EFFECTS OF NUTRITION ON NEUROTRANSMITTER CONCENTRATIONS AND
ASSOCIATED BEHAVIOURS
Important neurotransmitters are synthesized from compounds which are essential dietary
constituents.
For instance, Nor-Epinephrine (NE) and Serotonin are formed from the essential amino
acids Tyrosine and Tryptophan respectively.
Choline for Acetylcholine (Ach) synthesis can be obtained from either brain choline, the
phosphatidylcholine in the membranes of serum choline.
A. GLUCOSE
Normally provides the acetyl moiety of ACh.
Extensive evidence indicates that relatively modest increases in circulating glucose
concentrations can also increase ACh release and has been claimed to enhance learning
and memory.
Glucose enhances learning and memory in healthy aged humans and improves several
other cognitive functions in subjects with severe cognitive pathologies, including
individuals with Alzheimer’s disease and Down’s syndrome.
Moderate increases in circulating glucose concentrations may have robust and broad
influences on brain functions that span many neural and behavioral measures.
B. TRYPTOPHAN
Tryptophan crosses the blood-brain barrier predominantly by the carrier system for long-
chain neutral amino acids.
Serotonin (5-Hydroxytraptamine, 5-HT) synthesis depends on brain tryptophan, which in
turn depends on blood tryptophan concentrations, which can be manipulated by varying
the diet. Elevating tryptophan in the brain produces physiologically important changes in
the serotonergic system.
2
, Therapeutically, tryptophan has been reported to be useful in treating subgroups of
patients with depression, sleeplessness or hyperactive behaviours.
C. TYROSINE
Tyrosine is the precursor of Nor Epinephrine (NE) and Epinephrine.
Increasing Tyrosine reduces blood pressure in both normotensive and hypertensive
animals.
The action of tyrosine on blood pressure occurs via CNS mechanisms.
The antihypertensive action of tyrosine appears to be mediated by an acceleration in NE
or epinephrine release within the CNS.
Tyrosine induces increased NE and alters NE and α and β receptor densities in
hippocampus, providing further evidence of its physiological role.
III. EFFECTS OF NUTRITION ON BRAIN ENERGY RESERVE
Brain energy metabolism can be manipulated by diet.
A high-fat (90% of caloric value), carbohydrate-free ketogenic diet low in protein (10%)
does not significantly alter regional brain glucose utilization or cerebral concentrations of
glucose, glycogen, lactate or citrate.
A high-carbohydrate diet (78%) low in fat (12%) and low in protein (10%) markedly
decreases brain glucose utilization and increases cerebral concentrations of glucose 6-
phosphate.
Marginal protein dietary deficiency when coupled with carbohydrate-rich diet depresses
cerebral glucose utilization to a degree often seen in metabolic encephalopathies.
IV. REGULATION OF NORMAL NEURONAL ACTIVITY BY VITAMIN
Many vitamins function as cofactors in fundamental pathways, such as glycolysis, the
Krebs cycle, the respiratory chain and amino acid metabolism.
3
I. CEREBRAL METABOLISM
The brain is metabolically one of the most active of all organs in the body.
The brain does not store excess energy and derives almost all of its energy needs from
aerobic oxidation of glucose.
It requires a continuous supply of glucose and oxygen to meet its energy requirements.
Most of the brain’s energy consumption is used for active transport of ions to sustain and
restore the membrane potentials discharged during the process of excitation and
conduction.
When blood flow to the brain stops and absence of oxygen and blood occurs, a loss of
consciousness results in 5-10 seconds.
If the blood flow is not resumed within several minutes, there is permanent brain damage.
During crises, such as cardiac arrest, damage to the brain occurs earliest and is most
decisive in determining the degree of recovery.
The absence of glucose is equally destructive, but the time course resulting in irreversible
damage from hypoglycemia is longer because other substrates can be used.
Glucose metabolism is the major energy source for the brain.
Glucose from the blood enters the brain with help of GLUT-1 transport protein.
Once inside a brain cell, it enters the glycolytic pathway, where it is converted to
pyruvate and then metabolized through the Krebs cycle to generate ATP.
A fraction of ATP molecules is used to generate high energy phosphocreatine molecules.
Under certain conditions, aerobic metabolism of phosphocreatine to maintain normal
function. When brain failure occurs, there is loss of phosphocreatine initially, followed
by ATP depletion, which generally signals severe damage to the brain.
Hypoglycemia, which can result from excessive insulin is associated with changes in
mental state. These changes can be rapidly reversed by glucose administration as during
starvation, the brain can use “ketone bodies” in place of glucose as substrates.
Ketone Bodies, Acetoacetate and D-β-Hydroxybutyrate are formed from catabolism of
fatty acids by the liver.
The ketone bodies are metabolized to generate Acyl-CoA which enters the Tricarboxylic
Acid Cycle (TCA) at a sufficient rate to meet the metabolic demand of the brain.
1
,II. EFFECTS OF NUTRITION ON NEUROTRANSMITTER CONCENTRATIONS AND
ASSOCIATED BEHAVIOURS
Important neurotransmitters are synthesized from compounds which are essential dietary
constituents.
For instance, Nor-Epinephrine (NE) and Serotonin are formed from the essential amino
acids Tyrosine and Tryptophan respectively.
Choline for Acetylcholine (Ach) synthesis can be obtained from either brain choline, the
phosphatidylcholine in the membranes of serum choline.
A. GLUCOSE
Normally provides the acetyl moiety of ACh.
Extensive evidence indicates that relatively modest increases in circulating glucose
concentrations can also increase ACh release and has been claimed to enhance learning
and memory.
Glucose enhances learning and memory in healthy aged humans and improves several
other cognitive functions in subjects with severe cognitive pathologies, including
individuals with Alzheimer’s disease and Down’s syndrome.
Moderate increases in circulating glucose concentrations may have robust and broad
influences on brain functions that span many neural and behavioral measures.
B. TRYPTOPHAN
Tryptophan crosses the blood-brain barrier predominantly by the carrier system for long-
chain neutral amino acids.
Serotonin (5-Hydroxytraptamine, 5-HT) synthesis depends on brain tryptophan, which in
turn depends on blood tryptophan concentrations, which can be manipulated by varying
the diet. Elevating tryptophan in the brain produces physiologically important changes in
the serotonergic system.
2
, Therapeutically, tryptophan has been reported to be useful in treating subgroups of
patients with depression, sleeplessness or hyperactive behaviours.
C. TYROSINE
Tyrosine is the precursor of Nor Epinephrine (NE) and Epinephrine.
Increasing Tyrosine reduces blood pressure in both normotensive and hypertensive
animals.
The action of tyrosine on blood pressure occurs via CNS mechanisms.
The antihypertensive action of tyrosine appears to be mediated by an acceleration in NE
or epinephrine release within the CNS.
Tyrosine induces increased NE and alters NE and α and β receptor densities in
hippocampus, providing further evidence of its physiological role.
III. EFFECTS OF NUTRITION ON BRAIN ENERGY RESERVE
Brain energy metabolism can be manipulated by diet.
A high-fat (90% of caloric value), carbohydrate-free ketogenic diet low in protein (10%)
does not significantly alter regional brain glucose utilization or cerebral concentrations of
glucose, glycogen, lactate or citrate.
A high-carbohydrate diet (78%) low in fat (12%) and low in protein (10%) markedly
decreases brain glucose utilization and increases cerebral concentrations of glucose 6-
phosphate.
Marginal protein dietary deficiency when coupled with carbohydrate-rich diet depresses
cerebral glucose utilization to a degree often seen in metabolic encephalopathies.
IV. REGULATION OF NORMAL NEURONAL ACTIVITY BY VITAMIN
Many vitamins function as cofactors in fundamental pathways, such as glycolysis, the
Krebs cycle, the respiratory chain and amino acid metabolism.
3
