Cellular Homeostasis

Question 1

Metabolite homeostasis

Answer 1

glucose uptake

balance between glycolysis and gluconeogenesis

Question 2

GLUT1

Answer 2

ubiquitous
found in rbcs, cornea, brain, cancer cells, placenta
Km 1 mM
unregulated

Question 3

GLUT2

Answer 3

found in liver, pancreas, proximal convoluted tubules
unregulated/unresponsive to insulin
Km 10 mM

Question 4

GLUT3

Answer 4

found in neurons, unregulated, Km 1 mM

Question 5

GLUT4

Answer 5

found in skeletal muscle, adipose tissue, heart
regulated by insult

surface expression of GLUT4 dependent on insulin
km 5 mM, normally 50% saturated

Question 6

how does insulin cause expression of GLUT4?

Answer 6

GLUT4 in microvesicles in cell, insultin signaling causes fusion of these vesicles to membrane

Question 7

Glucose supply

Answer 7

dietary (galactose/fructose/glucose)
glycogenolysis (glycogen breakdown) 
gluconeogenesis (de novo): 
      made from 
            1. lactate 
            2. Glycerol 
            3. glucogenic amino acids 
            4. TCA cycle intermediates

Question 8

Franconi Bickel Syndrome

Answer 8

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

Question 9

GLUT2 in Glucose sensing

What they do, where they’re located, what they are “considered”

Answer 9

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”

Question 10

GLUT2 in Glucose sensing

how they actually work (the mechanism)

Answer 10

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

Question 11

Glucose tolerance test

Answer 11

tests for type II diabetes:

administration of glucose followed by 8-12 hours of fasting period

tests blood before administration and then during intervals

Question 12

Glucose tolerance test

Glucose plasma levels (5)

Answer 12

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

Question 13

less than 6.1

Answer 13

normal glucose levels during fasting

Question 14

6.1-7

Answer 14

borderline

Question 15

after 2 hours of glucose administration, plasma level should be

Answer 15

less than 7.8

Question 16

between 7.8-11.1

Answer 16

impaired glucose tolerance

Question 17

glucose levels higher than 11.1

Answer 17

diabetes

Question 18

five broadly categorized functions for protein homeostasis

Answer 18

proper synthesis 
folding 
post translational modifications 
transport 
clearance/degradation of damaged proteins

Question 19

Regulation of protein synthesis at the transcriptional level

transcription factors

Answer 19

trans-acting proteins that regulate gene transcription
have DNA binding domain
promote or repress transcription of target genes, which eventually regulates translation

Question 20

PEPCK

Answer 20

Phosphoenolpyruvate Carboxykinase

key enzyme in the synthesis of glucose in the liver and kidney?

Question 21

Chaperson/Enzymes

Answer 21

help correct folding of new synthesized proteins

Question 22

HSP70

Answer 22

helps in folding new and proteins

Question 23

HSP90

Answer 23

helps in folding new subset of proteins (???)

Question 24

Transport of proteins to their final destination: mitochondria example

Answer 24

protein precursor binds to TOM complex which inserts protein into outer memberane, and TIM complex inside translocates it into innter mito membrane

Question 25

post translational modifications (PTMs)

Answer 25

function
regulation
subcellular localization
interaction with other molecules
degradation

Question 26

PTM

acylation

Answer 26

attachement of an acyl group (eg fatty acids)

example: acylation of G proteins with palmitic acid or myristic acid affects their attachment to subcellular membranes

Question 27

PTM

glycation and glycosylation

Answer 27

nonenzymatic attachment of glucose. glycation: or enzymatic attachment of a number and variety of sugars (glycosylation)

glycation- nonenzymatic attachment of sugars
glycosylation- enzymatic attachment of sugars

example: glycosylation of erythrocyte membrane proteins defines an individual’s blood type

Question 28

phosphorylation

Answer 28

attachment of a phosphate group (PO4) via an ester bond

phosphorylation inhibits some proteins

Question 29

ubiquination

Answer 29

attachment of a small protein called ubiquitin

tags for destruction

Question 30

PTM

extracellular degradation

Answer 30

enzymes are degraded extracellularly by proteolytic enzymes as needed

secreted as inactive precursors zymogens

Question 31

Organelle homeostasis

Answer 31

autophagy or autophagocytosis

breaks down dysfunctional proteins
ensures synthesis, degradation, and recycling of cellular components

Question 32

Model of autophagy

Answer 32

nucleation of membrane components, and their extension

closure around some cytosol and organelles

fusion with lysosomes

digestion

Question 33

Mitochondria functions

Answer 33

beta-oxidation of fats
TCA cycle
Urea cycle
storage of Ca2+

Question 34

How does mitochondria maintain homeostasis?

Answer 34

fission: to create new mitos
fusion: helps mitigate damage caused by dysfunctional mitos