Cellular Homeostasis Flashcards Preview

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Flashcards in Cellular Homeostasis Deck (34):
1

Metabolite homeostasis

glucose uptake
balance between glycolysis and gluconeogenesis

2

GLUT1

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

3

GLUT2

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

4

GLUT3

found in neurons, unregulated, Km 1 mM

5

GLUT4

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

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

6

how does insulin cause expression of GLUT4?

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

7

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 intermediates

8

Franconi 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

9

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"

10

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

11

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

12

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

13

less than 6.1

normal glucose levels during fasting

14

6.1-7

borderline

15

after 2 hours of glucose administration, plasma level should be

less than 7.8

16

between 7.8-11.1

impaired glucose tolerance

17

glucose levels higher than 11.1

diabetes

18

five broadly categorized functions for protein homeostasis

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

19

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

20

PEPCK

Phosphoenolpyruvate Carboxykinase

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

21

Chaperson/Enzymes

help correct folding of new synthesized proteins

22

HSP70

helps in folding new and proteins

23

HSP90

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

24

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

25

post translational modifications (PTMs)

function
regulation
subcellular localization
interaction with other molecules
degradation

26

PTM

acylation

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

27

PTM

glycation and glycosylation

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

28

phosphorylation

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

phosphorylation inhibits some proteins

29

ubiquination

attachment of a small protein called ubiquitin
tags for destruction

30

PTM

extracellular degradation

enzymes are degraded extracellularly by proteolytic enzymes as needed

secreted as inactive precursors *zymogens*

31

Organelle homeostasis

autophagy or autophagocytosis

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

32

Model of autophagy

nucleation of membrane components, and their extension

closure around some cytosol and organelles

fusion with lysosomes

digestion

33

Mitochondria functions

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

34

How does mitochondria maintain homeostasis?

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