Cellular Homeostasis Flashcards
Metabolite homeostasis
glucose uptake
balance between glycolysis and gluconeogenesis
GLUT1
ubiquitous
found in rbcs, cornea, brain, cancer cells, placenta
Km 1 mM
unregulated
GLUT2
found in liver, pancreas, proximal convoluted tubules
unregulated/unresponsive to insulin
Km 10 mM
GLUT3
found in neurons, unregulated, Km 1 mM
GLUT4
found in skeletal muscle, adipose tissue, heart
regulated by insult
surface expression of GLUT4 dependent on insulin
km 5 mM, normally 50% saturated
how does insulin cause expression of GLUT4?
GLUT4 in microvesicles in cell, insultin signaling causes fusion of these vesicles to membrane
Glucose supply
dietary (galactose/fructose/glucose)
glycogenolysis (glycogen breakdown)
gluconeogenesis (de novo):
made from
1. lactate
2. Glycerol
3. glucogenic amino acids
4. TCA cycle intermediatesFranconi Bickel Syndrome
arises because of a deficiency in GLUT2 transporter in liver, pancreatic beta cells, and proximal convoluted tubule
glucose not detected, so insulin not released.
two outcomes: glucose/galactose is not cleared from plasma after meals, and glucose generated in the liver is not released during fasting.
children/infants
outcomes:
hepatomegaly due to accumulation of glycogen in liver
dwarfism due to vitamin D depedent hypophosphatemic rickets due to proximal tubular nephropathy
vitamine D supplementation
GLUT2 in Glucose sensing
What they do, where they’re located, what they are “considered”
Located in the Pancreatic beta cells
Purpose is to maintain equilibrium between intracellular and extracellular glucose levels
uses facilitated diffusion
high capacity but low affinity for glucose
considered the “glucose sensors”
GLUT2 in Glucose sensing
how they actually work (the mechanism)
glucose is metabolized once in the cell to create ATP
ATP increase causes potassium channels to close
closing of potassium channels causes depolarization
depolarization causes voltage gated calcium channels to open
calcium influx causes release of insulin
calcium influx also causes activates cAM kinase which causes synthesis of insulin
Glucose tolerance test
tests for type II diabetes:
administration of glucose followed by 8-12 hours of fasting period
tests blood before administration and then during intervals
Glucose tolerance test
Glucose plasma levels (5)
less than 6.1 mM is the normal fasting level
6.1 - 7 mM is borderline
after 2 hours, plasma glucose should be less than 7.8 mM
between 7.8-11 mM- impaired glucose tolerance
larger than 11.1 mM indicates diabetes
less than 6.1
normal glucose levels during fasting
6.1-7
borderline
after 2 hours of glucose administration, plasma level should be
less than 7.8
between 7.8-11.1
impaired glucose tolerance
glucose levels higher than 11.1
diabetes
five broadly categorized functions for protein homeostasis
proper synthesis folding post translational modifications transport clearance/degradation of damaged proteins
Regulation of protein synthesis at the transcriptional level
transcription factors
trans-acting proteins that regulate gene transcription
have DNA binding domain
promote or repress transcription of target genes, which eventually regulates translation
PEPCK
Phosphoenolpyruvate Carboxykinase
key enzyme in the synthesis of glucose in the liver and kidney?
Chaperson/Enzymes
help correct folding of new synthesized proteins
HSP70
helps in folding new and proteins
HSP90
helps in folding new subset of proteins (???)
Transport of proteins to their final destination: mitochondria example
protein precursor binds to TOM complex which inserts protein into outer memberane, and TIM complex inside translocates it into innter mito membrane
