Brain lipids and myelin synthesis

📌 General Brain Metabolism

🧠 Brain = 2% of body weight but consumes:

20–25% of total body oxygen.

60% of total body glucose.

Main & first fuel = Glucose.

Glucose level effect:

70 mg/dL → all cells work normally.

50 mg/dL → some cells stop functioning.

40 mg/dL → only Brain + RBCs work.

<40 mg/dL → RBCs only continue working.

🖇 Comparison: Muscles vs. Brain vs. RBCs

Muscles:

Can use glucose, fatty acids, glycogen.

Have multiple energy sources & can rest.

Brain:

Cannot rest → must work continuously.

Depends only on glucose & ketone bodies.

RBCs:

Only use glucose (no mitochondria, no nucleus).

Depend on glycolysis + PPP.

Last cells to function at very low glucose.

📌 Brain Structure Notes

Glial Cells: act as insulators like electric wire covering.

Gray Matter: neuronal cell bodies (soma).

White Matter: axons, rich in lipids → white color.

🟠 Energy Sources

-Source Pathway End Product Carbohydrates (Glucose)Glycolysis → Pyruvate → Krebs Cycle → ETC→ATP

-Proteins → amino acids → Gluconeogenesis or Ketogenesis.→ Glucose / Ketone Bodies → Fats → Beta-oxidation → NADH, FADH → ETCATP

🚨 Clinical Note:

Acetone → evaporates in breath → fruity smell in prolonged fasting or uncontrolled diabetes.

Beta-hydroxybutyrate → measured to check for ketoacidosis.→ عشان هو مش متوفر في كل المعامل يستخدموا الاسيتون

📌 Fasting State Sequence

Early Phase:

Body uses Glycogen first.

Liver Glycogen: maintains blood glucose.

Muscle Glycogen: local use only.

Astrocytes: small glycogen store for brain cells.

After 8–14 hours:

Gluconeogenesis (GNG) starts → glucose from non-carbohydrate sources (mainly amino acids).

Maintains blood glucose between 60–115 mg/dL.

Prolonged Fasting:

Ketone bodies production increases → alternative brain fuel.

Types: Acetoacetate, Beta-hydroxybutyrate, Acetone.

🟣 Brain & Lipid Metabolism

Brain does NOT use beta-oxidation for energy.

Lipids in brain are used for:

Myelin sheath.

Cell membranes.

Neurotransmitters.

Special Oxidations (non-energy):

Alpha-oxidation → defect → Refsum Disease.

Peroxisomal oxidation → defect → Zellweger Syndrome.

Brain synthesizes Very Long Chain Fatty Acids (VLCFAs) internally → BBB prevents their entry.

📌 Pentose Phosphate Pathway (PPP)

Glucose-6-phosphate → PPP → produces:

NADPH:

Antioxidant.

Regenerates Glutathione.

Fatty acid synthesis.

Glucuronic acid synthesis.

Ribose-5-phosphate → nucleotide synthesis.

Glucuronic Acid → detoxification & conjugation.

🟠 Hormonal Regulation

State Main Hormone Action Effect Fed Insulin Dephosphorylation → activates enzymes↑ Glycogen synthesis, ↑ Lipogenesis

Fasting Glucagon Phosphorylation → activates catabolic enzymes↑ Glycogenolysis, ↑ Lipolysis, ↑ Ketogenesis

GLUT 1 & GLUT 3 in brain & RBCs are insulin-independent.

🚨 Clinical Importance

Prolonged fasting/uncontrolled diabetes → fruity breath smell (acetone).

Beta-hydroxybutyrate used to monitor diabetic ketoacidosis.

RBCs highly sensitive to glucose shortage → early hypoglycemia signs.

Brain defects:

Refsum Disease → alpha-oxidation defect.

Zellweger Syndrome → peroxisomal defect.