BCHE4040/LSCI5440-Aspects of

Neuroscience

Section 8: Nutrition and functional

neurochemistry

Kim Hei-Man CHOW, PhD

Assistant Professor
Room 604, Mong Man Wai Building
Biochemistry Program
School of Life Sciences
Email: [email protected]
 Today’s flow
1. Lecture 8’s content
2. Course evaluation (12pm)
Key learning objectives
Part 1: The importance of different nutrients to brain function
1. Brain as a chemical factory
2. Nutrients and their influences on:
A. Neurotransmitter concentration and associated behaviors
B. brain energy reserve
C. Normal neuronal activity
Part 2: Mental disorders and brain chemistry
1. Role of nutrients in mental health
2. Copper (Cu2+) overload
3. Vitamin B-6 deficiency
4. Amino acid imbalances
5. Fatty acid imbalances
6. The interface between Psychiatric Medication and Nutrient Therapy
 The brain is a chemical factory
1. Effective brain function requires a proper
concentration of neurotransmitters in specific area of Serotonin
the brain
2. These complex chemicals are continuously produced
by enzymatic reactions within special brain cells. For
example
I. Serotonin: synthesized in the raphe nuclei along
the brainstem and transported by axons to areas
throughout the brain
II. Dopamine: synthesized in several areas,
including substantia nigra and the ventral Dopamine
tegmental area
3. The primary raw materials for neurotransmitter
synthesis in the brain are nutrients: amino acids,
vitamins, minerals and other natural biochemicals
4. The levels of these ingredients are well-regulated for
most persons, but abnormalities can be resulted from
both deficiency or overload.
Nutrition can influence neurotransmitter concentrations and
associated behaviors
Important neurotransmitters are
synthesized from compounds which are
essential dietary constituents. Examples
are:
A. Norepinephrine—from essential
amino acid tyrosine, obtained from
diet
B. Serotonin—from essential amino
acid tryptophan, obtained from
diet
C. Dopamine—like norepinephrine,
also from essential amino acid
tyrosine, obtained from diet
 Tyrosine Tyrosine Tyrosine Tryptophan

Glutamine Choline Glutamine A small peptide (16-17 a.a.)

 Nutrition can influence brain energy reserve
1. Brain energy is more resistant to changes in fasting or overfeeding than that in liver or muscle.
2. However, brain energy metabolism can be manipulated by diet.

Experimental finding:
1. 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.

2. But a high-carbohydrate diet (78%) low in fat (12%) and low in protein (10%) markedly decreases
brain glucose utilization and increase cerebral concentrations of glucose-6-phosphate (inhibit
glycolysis)

Even marginal protein dietary deficiency when coupled with a carbohydrate-rich diet depresses cerebral
glucose utilization to a degree often seen in metabolic encephalopathies.
 Vitamins can regulate normal neuronal activity
1. Many vitamins function as cofactor in
fundamental pathways e.g. glycolysis, Krebs
cycle, the respiratory chain and amino acid
metabolism
2. Vitamins are particularly important to the brain
because of its high metabolic rates
3. Many of these are B complex vitamins
1. B-1 (thiamine)—cofactor of key enzymes of
the Krebs cycle, e.g. pyruvate
dehydrogenase, a-ketoglutarate
dehydrogenase
2. B-3 (niacin)—synthesis of NAD+
(metabolism), NADP+ (redox regulation)
3. B-6 (pyridoxine)—is necessary for the
biosynthesis of several neurotransmitters,
e.g. glutamate, GABA, serotonin
4. B-9 (folic acid)—plays a key role in the
transfer of one-carbon (active methylene)
groups, including the conversion of serine
to glycine
 Mental disorders
WHO definition:
• They comprise a broad range of problems, with different symptoms.
However they are generally characterized by some combination of
abnormal thoughts, emotions, behavior and relationships with
others.
• Examples are schizophrenia, depression, intellectual disabilities and
disorders due to drug abuse

Causes (Mayo)—a variety of genetic and environmental factors:

1. Intertied traits: more common in people whose blood relatives also
have mental illness. Some genes may increase the risk of
developing mental illness
2. Environmental exposures before birth: toxins, alcohol or drugs to
the fetus while still the womb can sometimes trigger mental illness.
3. Brain chemistry: Neurotransmitters are naturally occurring brain
chemicals that carry signals to other parts of the brain and body.
When the neural networks involving these chemicals are impaired,
the function of nerve receptors and nerve system change, leading
to depression and other emotional disorders
 The decisive role of nutrients in mental health—The repeated
offenders
1. Scientists have realized that there are repeated presence of certain biochemical imbalances in completely different mental
disorders.:
A. Copper overload
B. Vitamin B6 deficiency
C. Amino acid imbalances
D. Fatty acid imbalances

2. These seemingly unrelated factors are common in the sense that: they all have a direct role in the synthesis or functioning
of a major neurotransmitter
3. Sometimes, the situation is complicated since a mental illness may involve more than one imbalance:
1. Antisocial personality disorder associated with criminality usually involves the combination of zinc deficiency,
oxidative overload, undermethylation, folate deficiency and elevated toxic metals.
2. Paranoid schizophrenia usually involves over-methylation, folate deficiency and elevated blood copper.
 Copper (Cu2+) overload
1. In most persons, blood copper levels are kept in
narrow range through the action of metallothionein,
ceruloplasmin and other metal binding proteins.
2. Many people may have a genetic inability to regulate
copper level and results in a serious copper overload
3. Copper: a cofactor in the synthesis of
norepinephrine—a neurotransmitter associated with
several mental illness
4. Norepinephrine—is formed by the addition of a
hydroxyl group to a dopamine molecule, catalyzed by
dopamine-β-hydroxylase (DBH) together with several
Cu2+, vitamin C and O2 cofactors.
5. Cu2+ overload tend to increase norepinephrine level in
the expense of dopamine level
6. Mental disorders associated with
dopamine/norepinephrine imbalances:
1. Paranoid schizophrenia
2. Bipolar disorder 5. Autism
3. Postpartum depression 6. Violent behavior Pleasure Concentration
4. ADHD
 Vitamin B-6 deficiency
Tryphtophan decarboxylase
PLP (Vitamin B-6)

1. Vitamin B-6 concentrations in the brain are about 100 times higher
than levels in the blood important for mental functioning.
2. Involved in more than 80 biochemical reactions in the body, B-6
deficiency can result in a wide variety of symptoms (insomnia, Mood
nervousness, muscle weakness etc.) that are often vague and DOPA decarboxylase
difficult to diagnose PLP (Vitamin B-6)

3. There are 3 different chemical forms of B-6, the most common

being pyridoxine hydrochloride, which converts to pyridoxal-5-
phosphate (PLP/P5P), the active form of B-6
4. PLP is a strong aldehyde that enables the removal of carboxyl
(COOH) groups from molecules Pleasure
5. B-6 is required by efficient synthesis of:
A. Serotonin Glutamate decarboxylase
PLP (Vitamin B-6)
B. Dopamine
C. GABA
6. Severe deficiency of B-6 has been associated to:
A. Serotonin (clinical depression, OCD)
B. Dopamine and GABA (ADHD, depression, anxiety and sleep Calming effect
disorders)
 Amino acid imbalances
1. A number of amino acids have important roles in
brain chemistry.
2. Most of the people receive ample amounts of
these amino acids from dietary protein and have
proper concentrations in the brain. However,
genetic errors at different levels may alter the
amounts of these amino acids in the brain thus
adversely impact mental functioning.
3. Examples:
A. Tryptophan—serotonin synthesis
B. Phenylalanine/tyrosine—dopamine and nor-
epinephrine synthesis
C. Glutamine—for glutamate and GABA synthesis
D. Histidine—for histamine synthesis
 Fatty acid imbalances

1. There are more than 300 different types of fat species in the human brain
2. The brain has a very high fat content (about 65%)
3. Unsaturated fatty acids are especially important as they provide fluidity to cell membranes and assist
synaptic vesicle formation.
4. At brain synapses, four types of fats make up more than 90% of the lipid content:
1. Docosahexaenoic acid (DHA)—omega-3 FA
2. Eicosapentaenoic acid (EPA)—omega-3 FA
3. Arachidonic acid (AA)—omega-6 FA
4. Dihomo-gamma-linolenic acid (DGLA)—omega-6 FA
5. DHA is found in highest concentration and appears to have the greatest impact on brain function,
deficiency is associated with: depression, ADHD, schizophrenia, bipolar disorder and dementia.
The interface between Psychiatric Medication and Nutrient
Therapy
Psychiatric Medication:
Most patients (e.g. schizophrenic) are taking psychiatric mediation at the time of first appointment and express
a desire to discontinue the drugs
1. Medications: fast, instant (within a few hours or days)
2. Example: SSRI anti-depressants quickly bind to transporters, resulting in a rapid increase in serotonin
activity at the synapse
3. But low compliance due to side effects (drowsiness, restlessness, nausea, diarrhea, sex problems etc.), and
short lasting (once off, the effect will be gone)

Nutrient Therapy:
1. Can have powerful impact on mental functioning, but several weeks or months are usually needed to
achieve full effect
2. Example: elimination of copper overloads in the blood usually requires about 60 days; zinc deficiency
usually can be corrected again in 60 days
Important concepts
1. Effective brain function requires a proper concentration of neurotransmitters in specific area
of the brain and this depends on proper nutrition.
2. Nutrition can influence neurotransmitter concentrations and associated behaviors, brain
energy reserve and neuronal activity.
3. Different amino acids act as the raw substrate for the synthesis of various neurotransmitters.
4. High fat versus high carbohydrate diet and their effect towards brain energy reserves.
5. Vitamin B complexes are important in maintaining normal neuronal function
6. Mental disorders is an umbrella term for a broad range of problems, with different
symptoms in the brain, the causes could be genetic, environment and altered brain
chemistry.
7. Repeated presence of certain biochemical imbalances in completely different mental
disorders: Copper overload, vitamin B6 deficiency, amino acid imbalances, fatty acid
imbalances and glucose dysregulation; and the reason why they are disturbing brain
functions
8. The pros and cons between psychiatric medication and nutrient therapy
Concept check (T/F)
1. Norepinephrine and dopamine are formed from tryptophan
2. Serotonin is form from tyrosine
3. Our brain energy reserve is more affected by high-fat diet over high carbohydrate diet
4. Vitamins are important because they can be serving as cofactor in fundamental fuel metabolic pathways
5. B-1 (thiamine) facilitates the synthesis of NAD+ and NADP+
6. B-6 (pyridoxine) is necessary for the biosynthesis of several neurotransmitters, e.g. glutamate, GABA,
serotonin, because it serves as the substrate
7. Mental disorders are solely due to genetic mutations
8. Copper overload can cause paranoid schizophrenia because it over produce norepinephrine from
dopamine
9. Vitamin B-6 helps to add a carboxyl group to glutamate, thus making more GABA
10.Glutamine can be used as the substrate for the synthesis of glutamate and GABA
11.Unsaturated fatty acids are especially important as they provide fluidity to cell membranes and assist
synaptic vesicle formation
12.Loss of omega-6 fatty acids appears to have the greatest impact on brain function
13.Nutrient therapy is good in long terms as it helps to correct the underlying dyshomeostasis of nutrients,
although time required to take effect is much longer than traditional psychiatric medication