MEDI211 Lecture Notes - Lecture 1: Alpha-Ketoglutaric Acid, Ketogenesis, Hypoglycemia
Week 2 Lecture 1 – Macronutrients storage to fire
Glycogenolysis in the skeletal muscle: glucose liberation:
•Epinephrine (neurotransmitter) is released during low blood glucose levels (BGL)-release
from adrenal medulla
•Epinephrine binds to B-adrenergic receptors (G protein-coupled receptors (GPCRs)) on the
muscle cell wall. This triggers a signal cascade inside the cell which results in the breakdown
of glycogen in glycogenolysis. Glycogenolysis: glycogen —> glucose-1-phosphate —>
Glucose-6-Phosphate—> glycolysis Epinephrine stimulates phosphorylation, whereas insulin
inhibits phosphorylation.
•Glycogenolysis occurs via a G-protein complex pathway, and needs adenylyl cyclase and
protein kinase (PKA).
•Protein Kinase A inhibits glycogen synthase, which is the enzyme needed to create glycogen
from glucose, thus prevents the reverse of glycogenolysis.
Glycogenolysis in the liver:
•Mostly triggered by glucagon —> glucagon receptor is expressed on the hepatocyte cell
wall. -Epinephrine released during low BGL-G-protein complex stimulates same pathway as
in skeletal muscle Glycogenolysis: glycogen —> glucose-1-phosphate —> Glucose-6-
Phosphate—> glucose
•This pathway inhibits glycogen synthase enzyme (cannot create glycogen).
•However in the liver, some glucose-6-phosphate is also transformed back into glucose and
released into the bloodstream so it can be used for the brain.
•After overnight fast, hepatic glucose output it derived from 50% glycogenolysis and 50%
gluconeogenesis
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Week 2 Lecture 1 – Macronutrients storage to fire
Lipolysis in adipocytes:
•driven by epinephrine, released from adrenal medulla; driven by B-adrenergic G-protein
complex.
•Initial pathway is exactly the same as in liver and muscle cells, except the protein kinase
pathway also activates hormone-sensitive lipase (HSL) which leads to lipolysis.
HSL determines how many FA circulate in bloodstream. It hydrolyses triglycerides —> fatty
acid + glycerol = lipolysis.
•In the blood, FA are transported bound to a carrier protein (eg. Albumin) and transported to
the site of demand.
•HSL is activated in response to decreased insulin (insulin inhibits HSL) or
increased epinephrine (as this activated the sympathetic nervous system)
•Growth hormone also stimulates HSL.
•HSL has the exact opposite effect to lipoprotein lipase (LPL), which stimulates the storage of
fat.
Glucagon:
•Main hormone that regulates BGL
•Basic role is to increase blood glucose levels —> opposite to insulin
•Primarily secreted from pancreatic-a cells when insulin is low (whereas insulin is released
from pancreatic-b cells)
•AAs, fasting and low BGL can stimulate glucagon release.
•Releases into bloodstream (like insulin but with opposite effects) so that liver can take it up
and release glucose for brain
•Stimulates glycogenolysis, gluconeogenesis, ketogenesis, lipolysis and proteolysis.
•Glucagon binds to glucagon receptor on hepatocyte; activates adenylyl cyclase pathway and
inhibits glycogenesis (inhibits glycogen synthase)
•Inhibits glycolysis (G-6-P —> pyruvate) by inhibiting enzymes that favour this pathway.
Once glucose is formed it cannot be transformed back into G-6-P.
•Promotes gluconeogenesis by activating enzymes for pyruvate. Any glucose that is stored in
the liver is been used for energy for cells that really need it - brain cells, blood cells through
glycolysis pathway.
•Glucagon promotes ketogenesis, as the hepatocytes must be using fat for their own energy as
all glucose is used for brain and blood cells.
•Directs breakdown of fat for ketosis —> ketone bodies can also be used by the brain to use
ATP once all glucose has already been directed to brain. Glucagon allows the brain to
function during fasting, however in long term situations it can lead to decreased blood
glucose levels and ketoacidosis.
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Epinephrine (neurotransmitter) is released during low blood glucose levels (bgl)-release from adrenal medulla. Epinephrine binds to b-adrenergic receptors (g protein-coupled receptors (gpcrs)) on the muscle cell wall. This triggers a signal cascade inside the cell which results in the breakdown of glycogen in glycogenolysis. Glucose-6-phosphate > glycolysis epinephrine stimulates phosphorylation, whereas insulin inhibits phosphorylation. Glycogenolysis occurs via a g-protein complex pathway, and needs adenylyl cyclase and protein kinase (pka). Protein kinase a inhibits glycogen synthase, which is the enzyme needed to create glycogen from glucose, thus prevents the reverse of glycogenolysis. Mostly triggered by glucagon > glucagon receptor is expressed on the hepatocyte cell wall. Epinephrine released during low bgl-g-protein complex stimulates same pathway as in skeletal muscle glycogenolysis: glycogen > glucose-1-phosphate > glucose-6- This pathway inhibits glycogen synthase enzyme (cannot create glycogen). However in the liver, some glucose-6-phosphate is also transformed back into glucose and released into the bloodstream so it can be used for the brain.
