Biochemistry Flashcards
What constitutes severe hypoglycemia?
Blood glucose levels of 40mg/100mL and below
What symptoms of hypoglycemia occur with lower and lower blood glucose levels?
Normal levels - no symptoms > Subtle neurological symptoms > Rlease of glucagon, epinephrine > Decreased attention, motor skills, sweating, hunger, drowsiness > Lethargy > coma > convulsions > Permanent damage > death
What are the sources of energy for the brain?
Glucose
Ketone bodies (starting ~4 days into fasting)
What ketone bodies are used as an energy source for the brain?
Acetoacetate
D-ß-Hydroxybutyrate
How does glucose hemostasis work on newborns?
Before birth = glucose comes from mother
At birth = newborn glucose falls –> hormonal stress response
- surge of glucagon, leading to glycogenolysis and gluconeogenesis
- ketogenesis is very active; ketone bodies needed to supplement glucose
How does baby and adult ketone body production differ?
Babies have more active ketone body production and utilization than an adult
even when well fed
What are the three energy systems of muscle and brain?
Immediate: Phosphagens
Short term: anaerobic glycolysis
Long term: aerobic glycolysis
What is the phosphagen system?
phosphocreatine + ADP –> ATP + Creatine
Enzyme: Creatine Kinase
How is the phosphagen system used/recovered?
Used:
Bursts of muscle contraction or pumping of ions across neuron membranes shift the rxn to the right
Recovered:
During periods of rest, or between muscle contractions at lower work levels, the rxn shifts to the left
Why is glucose so important for the body, apart from its use as a source of energy?
Glucose can be used to synthesize metabolic intermediates and neurotransmitters
As blood glucose leels drop and brain glucose levels diminish, synthesis of these NT may be compromised
Examples:
Aspartate
Glutamate
GABA
Glycine
What are the different levels of the blood brain barrier?
- Tight junctions btwn endothelial cells
- Narrow intercellular spaces
- lack of pinocytosis on endothelial cells
- Continuous basement membrane of endothelial cells
- Astrocyte extentions
How do compounds cross the BBB?
Through specific carrier proteins
Note: very lipophilic molecules may pass through all membranes in absence of carriers
What is the BBB permealble/impermeable to?
- *Permeable:**
- *Glucose** via GLUT1 and GLUT3 transporters
Aternative fuels (i.e. ketone bodies, lactate, acetate, pyruvate) via monocarboxylate transporter
Selected amino acids, essential fatty acids (what brain needs, but can’t synthesize)
Impermeable:
Most fatty acids
- fatty acid oxidation is not a significant source of ATP
What is the main excitatory neurotransmitter in the brain?
Glutamate
How does the astrocyte-neuron lactate shuttle work?
At glutamatergic synapses:
1. Glutamate is released into synaptic cleft and depolarizes post-syn. neuron
- This is terminated by efficient glutamate uptake systems (primarily on astrocytes) with a Na+/Glutamate cotransporter
- Increase in Na+ in astrocyte activates Na+/K+ ATPase, which activates glycolysis –> producing lactate
- Lactate can then be taken up by neurons and used as an energy source (made back into pyruvate and taken up by mitochondria)
- The energy produced by lactate then allows for more packaging of glutamate into vesicles to be released, again, into synaptic cleft
*Note glutamate taken up by astrocytes is trafficked back to neurons as glutamine (able to cross plasma membrane) then made back into glutamate in the neuron
How is GABA synthesized?
Produced by decarboxylation of glutamate and the GABA shunt:
