Energy Metabolism in the Brain Flashcards
Why does the brain need energy? (4)
- Energy heavy organ - using 20% oxygen and 25% of circulating glucose
- 15% of body’s total blood flow
- Supply and demand of energy requires dynamic adjustments in cerebral blood flow and glucose
consumption - Brain metabolism is highly compartmentalized and
numerous biochemical processes are involved - analogy: running a marathon all day, everyday
Different energy requirements of the brain (5)
- Glucose is the primary source of energy used by both neurons and astrocytes
- Lactate, a special role as a readily available source of energy
- Ketone bodies eg acetoacetate and β-hydroxybutyrate = essential substrates
- Age and development influences energy demand
- Distribution of energy amongst cell types vary
describe the change in substrate preference in line with development (2)
early brain dev: lactate + ketone - immediate postnatally => coincides w/ high fat content in milk of humans + animals
shift due to availability of substrate + changes in transport proteins = glucose
when else is lactate or ketone used as a substrate other than as a baby? (2)
When glucose isn’t available - ie extreme energy consumption (neuroinflammation)
ketone diets
How do we measure brain energy? (7)
- ATP production (primary energy currency - brain’s energy status, response to stim - norm vs abnorm)
- Rate at which glucose is consumed (brain’s utilisation of glucose)
- Rate of oxygen consumption (energy production)
- Lactate production and uptake (brain;s reliance to lactate)
- Cerebral blood flow (ensures delivery of O2 + gluc to meet energy demands)
- Mitochondrial function (measuring ATP synth, o2 consump. etc)
- Energy metabolism rate (holistic view of brain’s energy metab.)
what does recent evidence show about cell’s energy usage? (3)
major distribution of energy = uncertain how much
oligodendrocytes use less energy/metabolic rates than neutrophil regions eg astrocytes/ neurons
neuronal cell bodies glucose utilisation < astrocytes/ regions rich in synapses
Energy Metabolism def (1)
The set of chemical reactions and processes for acquiring, storing, and utilizing energy from nutrients (carbohydrates, fats, proteins)
Energy Metabolism background (4)
core process: catabolism of nutrients -> ATP
key processes: Glycolysis, TCA cycle (KREBS/citric acid cycle), oxidative phosphorylation, lipolysis etc
location: all cells esp liver, muscles, adipose
importance: Fundamental biological process, responsible for energy production
Energy homeostasis def (1)
The body’s capacity to maintain a stable
balance between caloric intake and
expenditure to maintain overall energy
equilibrium
Energy homeostasis background (4)
core process : Regulatory mechanisms controlling hunger, appetite, satiety + energy expenditure to avoid energy excess/deficiency
key processes: Neural and endocrine control mechanisms, especially involving the hypo
location: organism level - reg entire body energy balance
importance: Essential for maintaining healthy body weight and preventing obesity or excessive weight loss
Describe the makeup of the BBB (4)
metabolic barrier/ neurovascular unit
innermost = Brain capillary lumen
next layer = endothelial cells
3rd layer : basement membrane with pericytes in it
4th layer: astrocytes
What is a pericyte? (2)
specialised cell residing in the walls of capillaries + integral component of neurovasculature - maintains BBB integrity
What is the astrocyte’s role in the BBB? (2)
central role in the uptake of glucose from bloodstream to projections
= serves as a protective barrier b/w blood supply + neuron
Describe the pathway of glucose in the BBB (7)
glucose uptake via GLUT1 from brain interstitial fluid to endo cell
- conversion into pyruvate
- conversion into lactate
transport via MCT1/5 into BM
transport via MCT12 into pericyte
- lactate -> pyruvate conversion
- TCA cycle = ATP
CVO background (5)
organs w/o BBB + instead highly permeable capillaries (highly vascularised)
lining 3rd + 4th v of brain
act as windows of the brain
either sensory or secretory (or both)
serve as homeostatic monitoring centres = closely observing any systematic circulatory changes -> releasing neuropeptides into circulation
Explain the difference b/w secretory + sensory CVO’s (2)
sec: some release directly into bloodstream or CSF
sen: equipped to monitor the peripheral circulation + adapt accordingly to nay detected changes
Name the 2 main glucose transporter in brain metabolism + the differences b/w astrocytes + neurons (2 + 2)
- SLC2 family – Glucose transporters (Glut) - Na+ independent
- SLC16 family – MCT transporters - crucial role in facilitating glu + monocar acids into brain
A: (SLC2A1) GLUT1 + MCT 1/4
N : (SLC2A3) GLUT3 + MCT 2
why does glucose need transporters? (1)
because it’s hydrophilic
Discuss the change in transporter proteins in line w/ development in the Astrocytes + neurons (2)
During brain development:
there is high numbers of MGLUT1 but even higher numbers of MCT1 in the brain: due to lactate + ketone substrate preference + availability
during brain maturation + synaptogenesis:
switch to increase exponentially the number of MGLUT1 transporters and decrease in the number of MCT1 transporters due to the change in fuel pref to glucose
Is there a diff in the amount of glucose uptake in neurons + astrocytes? (1)
no - despite diff transport proteins, they take up approx equal proportions
How does the brain sense blood
glucose? (2)
Glucose sensing is achieved in 2 ways:
o Sensing blood glucose in tight capillaries via tanycytes - send projections into nuclei
o CVOs with leaky capillaries via neurons and tanycytes
where are tanycytes found? (1)
lie at interface b/w ventricles + ventricular CSF - mostly on floor of 3rd v
Name the anabolic pathways (1)
Biosynthesis: Several enzymatic pathways lead to the synthesis of biological molecules eg more enzymes or structures like hair
Name the catabolic pathways (2)
eg Glycolysis + Cellular respiration: Several enzymatic pathways break down small molecules eg sugars into even smaller molecules to release ATP
digestion: Several enzymatic reactions occur in our digestive tract to breakdown food into smaller molecules that can easily be absorbed into the
blood stream and into our cells
State the approx total energy use of teh brain (3)
- 21µmol ATP/g/min
– approx 75% = signalling
– approx 25% = maintaining non-signalling activity eg protein syn + degrad, nucleotide and phospholipid turnover, axoplasmic transport and mitochondrial proton leak
Why glucose? (4)
- Dynamic energy source = glycogen (glycolysis)
- glycolysis = Energy production & biosynthesis of:
Carbohydrates
Amino sugars
Neuromodulators
Amino acids
-pentose phosphate shunt pathway = NADPH formation + Nucleotide biosynthesis
- TCA cycle = Amino acids + neurotransmitters
Describe the steps of glycolysis (5)
1) glucose - 1ATP
—hexokinase—
2) glucose -6- phosphate
3) fructose -6- phosphate - 1 ATP
— phosphofructokinase 1—
4) Fructose-1,6 - bisphosphate
either anaerobic (+) or aerobic resp
- ana:
then aerobic
then TCA cycle/ kreb cycle
- aer:
malate- aspartate shuttle
then electron transport chain
then oxidative phosphorylation
What happens with glucose in the
brain - neurons vs astrocyte glucose metab (2)
- Neurons rely on oxidative metabolism ( or via lactate given by astrocytes via bloodstream)
- Astrocytes predominantly metabolizing glucose via glycolysis
