When neurons use Glutamate as neurotransmitter, they can’t re-uptake it directly

Astrocytes uptake glutamate through co-transport with 3Na ions

Astrocytes then convert glutamate to glutamine which can be transported into a neuron and be used again to synthesize glutamate in mitochondria within the neuron

Increased intra-astrocytic Na+ leads to activation of the sodium-potassium pump to bring the equilibrium back to the cell AND also stimulates glycolysis whereby LACTATE IS PRODUCED

Astrocytes get glucose from capillaries

Then do glycolysis with it and eventually produce 2 lactates from 1 glucose

The lactate then leaves the astrocytes and neurons are free to pick it up and use it as fuel

The Proposed Astrocyte-Neuron Lactate Shuttle

Pyruvate metabolism via PDC and the TCA cycle leads to the net production of 17 ATPs per lactate

Exchange of lactate between astrocytes and neurons is operated by monocarboxylate transporters (MCTs)

Brain metabolism in the neuron:

Glucose to G-6-P to F-6-P to F-1,6-BP to pyruvate to acetyl-CoA into the TCA Cycle

PFK-1 controlled – activated by: AMP & F-2,6-BP

Brain metabolism in the astrocyte

Glucose to G-6-P to F-6-P to F-1,6-BP to pyruvate to lactate

PFK-1 activity increased by [ATP]

Complete oxidation of 2 lactates produces about__________ATP

2 lactates equivalent to about 1 glucose, so about 34 ATPs

How does lactate get transported between cells?

MCTs are electroneutral and mediate the H+-coupled flux of lactate, pyruvate or other monocarboxylates across cell membranes of most tissues in the body. In the case of lactate, MCTs can operate in either the net inward or net outward direction, depending on the lactate and H+ gradients across the cell membrane. MCTs probably moves lactate OUT of cells that produce lactate by glycolysis and INTO cells that consume lactate.

MCT1 and MCT4 in astrocytes ensure lactate release MCT2 in neurons allows for uptake of the lactate.

Role of glycogenolysis in Astrocytes

In the Figure, reactions occurring in astrocytes but not in neurons are indicated by heavy arrows.

Glycogen breakdown in astrocytes occurs in response to transmitters

Brain turnover of glycogen is increased during activation

Alpha-KetoGlutarate is the precursor of Glutamine which ends up being the source of Glu for neurons (via Glutamine).

In young chickens, inhibition of glycogenolysis interrupts memory consolidation: !

What is cotransported with glutamate from the synaptic cleft?

Na+

The subsequent decrease in ATP in astrocytes activates which enzyme in which pathway?

PFK-1

The metabolism of lactate in neurons has which end products?

CO2

H2O

And lots of ATP: 17

The metabolism of lactate in neurons generates how much ATP?

17

Which enzyme’s activity would limit glycolysis in neurons and what controls that enzyme?