Brain Metabolism Flashcards
Fatty acids found in the brain
- Cerebrosides, ganglisides, plasmalogens, very long-chain fatty acids
- lots of long chain stuff for myelisn sheath–>very high turnover (lost during endocytosis for NT re-uptake)
- tight packing of myelin sheathsl achieved by using very long chains that stack well, ptotolopid protein, myeline basic protein
Sources of energy for brain
- well fed absorbtive state–>glucose from diet
- fasting: glcogenolysis and gluconeogenesis
- starvtion: ketone bodies
Glucose transporters in brian
GLUT-1: cross endothelisal membranes (high affinity)
GLUT-3: enter neurons
neither is responsive to insulin, glucose uptake constant
Moncarboxylate trasnporter
-transports ketone bodies, pyruvate, lactate, and acetate across blood/brain barrier
Substances that can cross blood/brain barrier
- passive diffusion: O2, H2O, CO2, N2O, NH2, hydrophobic drugs including EtOH, nicotine, diazepam (phenobarbitol does cross barrier but slower than expected because is bound to albumin in blood)
- Essential fatty acids and vitamins (specific transporters)
- some proteins (insulin, growth factors: receptor-mediated endocytosis)
- large neurtral amino acids (most are essential): L, V, I, M, H, W, F, Y, L-DOPA (share facilitative transporter)
- amino acids that are also neurotransmitters are blocked (Glu, Asp, GABA, Dopamine (remember DCC will act on L-DOPA so if you want to give it you also have to give a DCC inhibitor so it stays as dopa and can get through the barrier))
Amino acids that are neurotransmitors
- glutamine
- glutamate & aspartate (main excitatory neurotransmitters)
- Glycine and GABA (main inhibitory neurotransmitters)
- L-DOPA
Amino acids that are precursors to NTs
Y–>catecholamines
W–>serotonin
H–>histamine
Q–>GABA
usually involves decarboxylation of amino acid forming an amine: B6 (pyridoxal) dependent
Sources of ammonium in brain for gluatamine syntesis
- astroglial cells have glutamine synthetase to make Q from E and NH4+
- tranamination of aa (α-Kg)
- deamination of aa (aspariginase, glutamate dehydrognease, glutaminase although that would be uselesss sort of)
- purine nucleotide cycle (AMP)
- neurons turn glutamine to glutamate to GABA
- glutamine also use to transport excess NH4+ to the blood from brain
Synthesis of Glutamine and GABA in brain
- Astroglial cell takes up BCAA
- Use BCAA transaminase (with α-Kg) to get Glutamate (and BCKA)
- Use glutamine synthetase to get glutamine (NH4+ from blood or purine nucleotide cycle in neurons or glutaminase)
- Glutaminase used to make glutamate and NH4+
- Glutamate decarboxylase (PLP) makes GABA
GABA Cycle
- glial cells do the major uptake of GABA; they lack glutamate decarboxylase
- converted to glutamine using GABA shunt (convert GABA into krebs cycle intermediate til to get to α-Kg I guess) and then GDH
- glutamine goes back to neurons, back to beginning
Glutamate de novo synthesis in brain
- transamination of α-Kg (α-Kg from TCA, NH3 from BCAA)
- Glutamate dehydrogenase (here using NADPH) (reductive amination)
- Glutaminase (deamination, also produces NH4+)
Epilepsy
- associated with low GABA (amongst other causes)
- treated with GABA analogs or GABA reuptake inhibitors
Benzodiazepines
(eg. valium)–>binds GABA recpeptor and has a cooperative effect on GABA binding–>receptor hyperpolarizes membrane increasing firing threshold
- reduces anxiety
Phencyclidine
- PCP
- NMDA (glutamate) receptor antagonist
Acetylcholine
- excitatory NT
- requires choline from diet
- or PE metylated to PC by SAM (THF and B12 needed to recycle SAM)
- Phospholipase D cleaves choline from PC
- Phospholipase C clease phospholpase from PC
- also need Acetyl-CoA (from glucose metabolism)
