1. Serotonin (5-HT)
Synthesis:
Step 1: Conversion to 5-Hydroxytryptophan (5-HTP):
Enzyme: Tryptophan hydroxylase
Process: The enzyme tryptophan hydroxylase catalyzes the hydroxylation of tryptophan, an essential amino acid, converting it into 5-hydroxytryptophan (5-HTP).
Cofactors Required: Tetrahydrobiopterin (BH4) and oxygen.
Mechanism: BH4 acts as a cofactor, donating electrons, while oxygen adds a hydroxyl group (-OH) to the benzene ring of tryptophan, forming 5-HTP.
Step 2: Conversion to Serotonin:
Enzyme: Aromatic L-amino acid decarboxylase (also known as DOPA decarboxylase).
Process: 5-HTP is decarboxylated to form serotonin (5-hydroxytryptamine, 5-HT).
Cofactor Required: Pyridoxal phosphate (vitamin B6).
Mechanism: The enzyme removes a carboxyl group (-COOH) from 5-HTP, resulting in the formation of serotonin.
Significance:
Mood Regulation: Serotonin is crucial for maintaining mood balance and is often called the "feel-good" neurotransmitter. Low levels are associated with depression.
Appetite Control: It helps regulate hunger and satiety.
Sleep: Serotonin influences sleep cycles and is a precursor to melatonin.
Cognitive Functions: It aids in learning, memory, and cognitive processing.
Gastrointestinal Motility: Serotonin helps control bowel movements and functions.
Vasoconstriction: It causes the narrowing of blood vessels, which helps regulate blood flow.
Clinical Relevance:
Psychiatric Disorders: Imbalances in serotonin levels are linked to conditions such as depression, anxiety, and obsessive-compulsive disorder (OCD).
2. Melatonin
Synthesis:
Step 1: Conversion to N-acetylserotonin:
Enzyme: Arylalkylamine N-acetyltransferase (AANAT).
Process: Serotonin is acetylated to form N-acetylserotonin.
Mechanism: AANAT transfers an acetyl group from acetyl-CoA to serotonin, producing N-acetylserotonin.
Step 2: Conversion to Melatonin:
Enzyme: Hydroxyindole-O-methyltransferase (HIOMT).
Process: N-acetylserotonin is methylated to form melatonin.
Mechanism: HIOMT transfers a methyl group from S-adenosylmethionine (SAMe) to N-acetylserotonin, producing melatonin.
Significance:
Sleep-Wake Cycle: Melatonin regulates the sleep-wake cycle by signaling to the body when it's time to sleep, aligning the internal clock with external light-dark cycles.
Antioxidant Properties: Melatonin has antioxidant effects, protecting cells from oxidative stress.
Immune Function: It supports the immune system and has anti-inflammatory properties.
Clinical Relevance:
Sleep Disorders: Melatonin supplements are used to treat conditions like insomnia, jet lag, and circadian rhythm disorders.
3. Dopamine
Synthesis:
Step 1: Conversion to L-DOPA:
Enzyme: Tyrosine hydroxylase.
Process: Tyrosine is hydroxylated to form L-dihydroxyphenylalanine (L-DOPA).
Cofactors Required: Tetrahydrobiopterin (BH4) and oxygen.
Mechanism: BH4 acts as a cofactor, and oxygen adds a hydroxyl group to the benzene ring of tyrosine, forming L-DOPA.
Step 2: Conversion to Dopamine:
Enzyme: Aromatic L-amino acid decarboxylase.
Process: L-DOPA is decarboxylated to form dopamine.
Cofactor Required: Pyridoxal phosphate (vitamin B6).
Mechanism: The enzyme removes a carboxyl group from L-DOPA, resulting in the formation of dopamine.
Significance:
Movement Regulation: Dopamine is crucial for the coordination of voluntary movements.
Motivation and Reward: It plays a key role in the brain's reward system, influencing motivation, pleasure, and reinforcement learning.
Basal Ganglia Function: Dopamine is essential for the proper functioning of the basal ganglia, a brain region involved in movement control.
Clinical Relevance:
Parkinson's Disease: Characterized by low levels of dopamine in the brain, leading to movement disorders.
Schizophrenia: Linked to dysregulation of dopamine pathways.
Addiction: Dopamine pathways are involved in the mechanisms of addiction and reinforcement of addictive behaviors.
4. Noradrenaline (Norepinephrine)
Synthesis:
Conversion from Dopamine:
Enzyme: Dopamine β-hydroxylase.
Process: Dopamine is hydroxylated to form noradrenaline (norepinephrine).
Cofactor Required: Ascorbic acid (vitamin C).
Mechanism: The enzyme adds a hydroxyl group to the β-carbon of dopamine, converting it into noradrenaline.
Significance:
Attention and Alertness: Noradrenaline enhances focus and response to stimuli.
Fight-or-Flight Response: It activates the sympathetic nervous system, increasing heart rate, blood pressure, and blood glucose levels in response to stress.
Clinical Relevance:
Stress Response: Noradrenaline plays a critical role in how the body reacts to stress and emergencies.
5. Adrenaline (Epinephrine)
Synthesis:
Conversion from Noradrenaline:
Enzyme: Phenylethanolamine N-methyltransferase (PNMT).
Process: Noradrenaline is methylated to form adrenaline (epinephrine).
Cofactor Required: S-adenosylmethionine (SAMe) as a methyl donor.
Mechanism: The enzyme transfers a methyl group from SAMe to the amine group of noradrenaline, producing adrenaline.
Significance:
Acute Stress Response: Adrenaline enhances the body's fight-or-flight response by increasing heart rate, blood pressure, blood glucose levels, and airflow to the lungs, preparing the body for rapid action.
Clinical Relevance:
Emergency Situations: Adrenaline is crucial during acute stress or danger, helping the body respond quickly to threats.