Biochemistry · MU Pleven

69. Metabolism in Nerve Tissue. Synthesis and Degradation of Neurotransmitters: Acetylcholine, Dopamine, GABA.

Covers how neurons obtain energy from glucose and, during prolonged fasting, ketone bodies, and where ATP is spent in nerve tissue. It then takes acetylcholine, dopamine and GABA in turn, setting out each one's synthesis, storage and release, and breakdown, with the enzymes and cofactors involved. Clinical links are noted for each, such as myasthenia gravis, Parkinson's disease and epilepsy.

Inside: 3 sections · 6 labelled pictures · 10 flashcards · 3 min

Topic 69 of 76 in the MU Pleven syllabus for Biochemistry (Medicine, Year 2). The free AceMed note covers it in 3 sections, about 357 words (3 min of reading), with 10 flashcards.

In this note

  1. Metabolism in Nerve Tissue. Synthesis and Degradation of Neurotransmitters: Acetylcholine, Dopamine, GABA.
  2. Metabolism in Nerve Tissue
  3. Synthesis and Degradation of Neurotransmitters

Metabolism in Nerve Tissue

  • Nervous tissue is highly specialized and has unique metabolic needs.
  • Neurons depend mainly on glucose for ATP. They have very limited glycogen stores, so they rely on a continuous blood supply. In prolonged fasting, they begin using ketone bodies as an alternative fuel, which helps spare muscle protein from being broken down for gluconeogenesis.
  • ATP in neurons is mainly used to maintain ion gradients (Na⁺/K⁺ ATPase pumps), neurotransmitter synthesis, axonal transport, and vesicle release.

Synthesis and Degradation of Neurotransmitters

Acetylcholine (ACh)

Made in cholinergic neurons.

Synthesis

  • Formed from Choline + Acetyl-CoA
  • Enzyme: Choline Acetyltransferase
  • Acetyl-CoA comes from glucose metabolism in neurons
  • Choline is taken up from the synaptic cleft by active reuptake transporters

Storage & Release

  • Stored in synaptic vesicles
  • Released when Ca²⁺ enters the neuron during depolarization

Degradation

  • Enzyme: Acetylcholinesterase (AChE) located in the synaptic cleft
  • Breaks ACh into Choline + Acetate
  • Choline is recycled back into the neuron

Clinical relevance

  • AChE inhibitors (e.g., neostigmine, physostigmine) ↑ ACh levels
  • Used in myasthenia gravis and reversal of anesthesia
  • Organophosphate poisoning causes dangerous accumulation of ACh

Dopamine (DA)

Made in dopaminergic neurons in substantia nigra and ventral tegmental area.

Synthesis (Amino acid precursor: Tyrosine)

  • Tyrosine → DOPA (enzyme: Tyrosine Hydroxylase, rate-limiting)
  • DOPA → Dopamine (enzyme: DOPA Decarboxylase)

Cofactors

  • Tyrosine hydroxylase requires BH4
  • DOPA decarboxylase requires Vitamin B6 (Pyridoxal phosphate)

Storage & Release

  • Stored in vesicles using VMAT transporter
  • Released upon nerve stimulation

Metabolism / Inactivation

  • Enzymes: MAO (monoamine oxidase) and COMT (catechol-O-methyl transferase)
  • Breakdown products eventually excreted in urine as VMA and HVA

Clinical relevance

  • Parkinson’s: loss of dopaminergic neurons → treat with L-DOPA
  • Schizophrenia: ↑ dopamine signaling → treat with dopamine antagonists
  • MAO and COMT inhibitors are used to boost dopamine in PD

GABA (Gamma Aminobutyric Acid)

Primary inhibitory neurotransmitter in the CNS.

Synthesis (from Glutamate)

  • Glutamate → GABA
  • Enzyme: Glutamate Decarboxylase (GAD)
  • Cofactor: Vitamin B6 (Pyridoxal Phosphate)

Storage & Release

  • Stored in inhibitory synaptic vesicles
  • Released to hyperpolarize postsynaptic membranes via Cl⁻ influx

Degradation

  • Enzyme: GABA transaminase
  • End product: Succinic semialdehyde → enters TCA cycle

Clinical relevance

  • B6 deficiency → ↓ GABA → seizures
  • Benzodiazepines and barbiturates enhance GABAergic activity
  • Vigabatrin inhibits GABA transaminase → ↑ GABA levels (used in epilepsy)

Continue reading free

The whole note, all 3 sections, is free with an AceMed account, with its 10 flashcards. Premium adds flashcard recall, highlights and Ask AI.

Start freeAlready a member? Open the note