Maintaining Glucoes- Lecture 9/20/21 Flashcards
Adrenergic response
Response to hypoglycemia, minor symptoms including trembling, palpitations, sweating etc
Neuroglycopenic response
Severe hypoglycemia (<54 mg/dL), more severe symptoms including confusion weakness drowsiness
Glucagon synthesis
In alpha pancreatic cells
Glucagon target tissues
Liver and adipose signals
Insulin made in
Beta cells of the pancreas
Insulin targets
Liver, adipose tissue, skeletal muscle
Glycogen
stored poly glucose, sustains blood levels for a few hours after meal
Glucose o genesis
De novo glucose synthesis, many days after eating
Hours after eating dominant form
Food glucose to about 4 hours, glycogen glucose from 4-16, gluconeogenesis from 16+
(Glycogen runs out after about a day(
Glycogen structure
Linked alpha 1-4 with 1-6 branches
Phosphoglucomutase
Rearranges glucose-6-phosphate to glucose-1-phosphate
Glycogenin
Initiates glycogen synthesis by self-glycosylating
Glycogen synthase
Adds single nucleotide glucoses to the growing chain, major regulated enzyme of glycogen synthesis
Branching enzyme
Takes 7 glucoses off of the growing chain and transferred to 1-6 linkages
Glycogen phosphorylase
Cleaves a glucose of the glycogen during breakdown, product is glucose-1-phosphate, major regulated step, can’t cleave within 3 glucoses of a branch
Debranching enzyme
Cleaves three off a branch and puts it on another chain 1-4 linkages, cleaves the last one to free glucose
enzyme differences in muscle and liver
Muscle lacks glucose-6-phosphatase, can’t export glucose uses it for itself
Insulin effect on glycogen
Stimulates synthesis
Glucagon effect on glycogen
Stimulates break down
Phosphorylase kinase
Phosphorylates glycogen phosphoryalase, more active when phosphorylated,
Phosphorylase kinase regulation
“A”form is more active because it is phosphorylated by phosphorylase kinase, glucagon istimulates and insulin inhibits
Phospho-glycogen synthase
Less active, protein kinase stimulated by glucagon
Cellular locations of gluconeogenesis
Mitochondria: Pyruvate carboxylase rxm
Cytoplasm: Most rxns
ER: glucose-6- phosphatase rxn
Pyruvate carboxylase
Pyruvate to oxaloacetate
PEP carboxylase
Oxaloacetate to PEP
Biotin
Cofactor for PEP carboxylase,
Oxaloacetate shuttle
Turned to malate or aspartate in mitochondrial matrix, shuttled out and regenerated, (making an NADH in the cytoplasm needed for gluconeogenesis)
Fructose 1,6 bishosphatase
fructose 1,6 bisphsphate to fructose 6 phosphate, highly regulated, inhibited by fructose 2 6 bisphoshate
Regulators for glucose oxidation
Stimulators: Insulin, F2,6 BP, AMP
Inhibitors: AMP
Regulators of Glucose synthesis
Stimulants: Glucagon, epinephrine, cortisol, Acetyl-CoA, Citrate
Inhibitors: F 2,6 BP, AMP
Regulators of Fructose 1,6 bisphosphatase
Inhibitors: AMP, F2,6, BP
Activators: Citrate
Cori cycle
Lactate (and alanine) created in muscle can be transported into the liver and made into glucose (for muscle)
Von Gierke disease
Type one GSD, Defect in glucose-6-phosphatase, can’t export glucose
Cori’s disease
Debranching enzyme defect, like van gierke but milder
McArdle disease
Skeletal muscle glycogen phosphorylase defect, usually seen in adulthood and does not effect liver