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Biochem intercellular signals metabolism of glucose
KYCOM Block 3
92
Biochemistry
Graduate
10/12/2012

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Term
What is intracellular signaling
Definition
Signals arise within the cell due to allosteric regulation and substrate concentrations
Term
What is intercellular signaling
Definition
Signaling between differs cells, coordinate developmental and survival activities
Term
What are the types of intercellular signaling
Definition
Direct contact, synaptic signaling, endocrine signaling
Term
What occurs during direct contact signaling
Definition
Signals sent between layers of cells at periphery of tissues via gap junctions
Term
When is direct contact signaling used
Definition
Wen cells are not in good contact with vessels
Term
What does direct contact signaling share with the other cells
Definition
mRNA, cell cycle regulators, evidence of pathogen invasion, etc
Term
What occurs in synaptic signaling
Definition
Signaling is carried out using neurotransmitters
Term
What occurs in endocrine signaling
Definition
Hormone is released in one location and travels to a receptor in another location
Term
War is the function of endocrine signaling
Definition
Coordinate multiple tissues, regulate and coordinate metabolism
Term
I general, what is a g-protein coupled receptor classified as
Definition
Integral membrane protein
Term
What is a g-protein coupled receptor specific
Definition
Because it can only interact with one ligand
Term
How is a g-protein coupled receptor structured? How many units does it have?
Definition
It has 7 transmembrane domains
Term
What does it mean when said that a g-protein is heterochromatic
Definition
It has 3 subunits: alpha, beta, gamma
Term
Wen is the G protein alpha subunit located when it is inactive
Definition
At the beta gamma subunit docking station
Term
How can G protein be stimulatory or inhibitory?
Definition
It can interact with the G protein coupled receptor to inhibit the process (Gi) or it can interact with the adenylyl cyclase to stimulate the process (Gs)
Term
When the Alpha subunit binds adenylyl cyclase, where does it bind
Definition
On the guanosine nucleotide
Term
What qualifies the alpha subunit of the G protein to be stimulator or inhibitor
Definition
If it is working with a stimulating G protein it is stimulating (Gas) when working with a inhibiting G protein it is and inhibitor (Gai)
Term
Once protein kinase A is activated, how does it actually effect the cell
Definition
It phosphorlyates target proteins which regulates flow of ions across membranes, regulates metabolic pathways using enzymes, acts as DNA binding protein and promotes or inhibits gene expression
Term
What are the steps in the first path we learned to initiate cellular response to intercellular signals
Definition
1. Ligand binds G protein coupled receptor
2. Receptor changes conformation on its inner cellular surface
3. G protein that is interacting with the receptor changes conformation
4. G protein changes GDP to GTP
5. G protein alpha subunit dissociates from the beta gamma dock
6. Alpha subunit changes conformation of adenylyl cyclase
7. Adenylyl cyclase generates cAMP using free ATP
8. cAMP activates protein kinase A by binding to its 2 regulatory subunits and release the two catalytic subunits
9. Protein kinase A phosphorlyates target proteins
10. Alpha subunit hydrolysis GTP to GDP
11. Alpha subunit dissociates from adenylyl cyclase
12. Alpha subunit docks with beta gamma dock
Term
In general, what is a adenylyl cyclase considered to be
Definition
An integral membrane enzyme
Term
In general, what is cAMP considered to be
Definition
Secondary messenger
Term
When a ligand binds a G protein coupled receptor, what changes occur in the G protein
Definition
It changes conformation changing GDP to GTP, the alpha subunit dissociates from the beta gamma subunit dock and goes off to find adenylyl cyclase
Term
What tools do adenylyl cyclase need to generate cAMP
Definition
G protein alpha subunit, ATP
Term
How does cAMP activate protein kinase a
Definition
It binds to its two regulatory subunits and causes the release of its two catalytic subunits
Term
What hydrolysis GTP back to GDP
Definition
G protein alpha subunit
Term
Way are the three ways to stop the first path of intercellular signaling
Definition
Remove the hormone (or other extra cellular signaling molecule), dephosphorlyate proteins, hydrolysis of cAMP
Term
What do protein phosphatses do
Definition
Hydrological lay cleave phosphate esters and remove effector proteins that are phosphorlyated by protein kinase
Term
What do cAMP phosphodiesterases do
Definition
Hydrolysis of cAMP, cleaves the phosphodiester bond turning it into 5'-AMP which is inactive
Term
Wy is removing the extra cellular signaling molecule not the most effective way of stopping a intercellular signaling chain
Definition
The effect can still keep going inside the cell
Term
Explain the process of cholerae infection
Definition
1. It enters the gut and releases cholera toxin
2. Toxin enters the epithelium and is endocytosed, only the elephant subunit enters the cell
3. Alpha subunit is clipped
4. Alpha subunit interacts with ADP ribosylation factor
5. The factor activates adenylyl cyclase permanently
6. Lots of cAMP is made so lots of protein kinase is made
7. Ca is released from the ER opening Cl channels
8. Cl drags positive ions (Na) and water out of the cell into large intestines
9. This much water cannot be absorbed so it causes dirreaha and denydration
Term
How is a cholerae infection treated
Definition
Water and electrolytes to replace the water lost, there isn't a problem absorbing the water just retaining it
Term
What causes the build up of water in the intestines in a cholerae infection
Definition
Ca release opens Cl channels and drags after and positive ions and water into the large intestines
Term
What are the steps in the second path we learned to initiate cellular response to intercellular signals
Definition
1. Ligand binds receptor
2. Receptor conformation changes activates Gq protein
3. Gq protein releases GDP and binds GTP
4. Gaq subunit detaches and activates phospholipid C
5. Phospholipid c cleaves the lipid bi layer into IP2, IP3, DAG
6. IP3 binds ER activating Ca channels releasing Ca into cytosol
7. DAG stays in the membrane, activating protein kinase C with the help of Ca
8. Ca and protein kinase C work together as a secondary messenger to turn on phosphorylation proteins
Term
Where is phospholipase C located
Definition
In the cell membrane
Term
What does phospholipase C do when activated
Definition
Cleaves the lipid bi layer into IP2, IP3, and DAG
Term
If in the liver and the ligand is epinephrine, what intracellular signaling process is activated, how does it happen
Definition
Glycogen degradation when epinephrine binds a1 adrenic receptor. Calcium binds cal moulin, this new complex changes conformation of enzymes in metabolism
Term
how do organs of metabolism communicate
Definition
nervous system, circulating substrates, hormones
Term
in metabolism, what do hormones signal for
Definition
to store or use energy
Term
what is coordination of the metabolism primairly regulated by
Definition
insulin and glucagon
Term
what is coordination of the metabolism secondairly regulated by
Definition
epinepherine and norepinepherine
Term
where is insulin produced
Definition
beta cells of the islets of langerhan in the pancreas
Term
what is insulin stored in
Definition
secretory granules
Term
where is glucagon produced
Definition
alpha cells of the islets of langerhan in the pancreas
Term
what type of effetor is insulin
Definition
anabolic
Term
what type of effector is glucagon
Definition
catabolic
Term
in general what does insulin affect, what does this cause
Definition
it affects glycogen, TAGs, and proteins. promotes glucose uptake
Term
in general, what does glucagon affect, what does this cause
Definition
affects glucose release from the liver. it causes gluconeogenesis and glycogenolysis
Term
what stimulates insulin to be released
Definition
increased blood glucose, amino acids, peptide hormones, glucagon decreases
Term
what do peptide hormones have to do with insulin
Definition
when produced due to response to food ingestion, they cause insulin to be released
Term
what stimulates glucagon
Definition
decreased amino acids, epinepherine
Term
what inhibits insulin
Definition
decrease in glucose or amino acids (fasting), increase in epinepherine
Term
what can causes increases in epinepherine in the body
Definition
stress, trauma, exercise
Term
what effect does epinepherine have on the body
Definition
increases glucagon, decreases glucose, affects mobilization of glucose from the liver and fatty acids from adipose
Term
in general, what inhibits glucagon
Definition
increasing glucose or insulin levels
Term
what are the types of glucose receptors
Definition
insulin sensitive and insulin insensitive
Term
what type of tissues are insulin insensitive receptors located
Definition
in tissues that require uptake of glucose but do not have a role in blood sugar regulation
Term
what tissues have insulin insensitive receptors and use active transport
Definition
epithelia of intestine, renal tubules, choroid plexus,
Term
what tissues have insulin insensitive receptors and use facilitative transport
Definition
RBC, WBC, lens of eye, cornea, liver, brain
Term
what type of transport do tissues with insulin sensitive receptors use
Definition
facilitated
Term
what tissues have insulin sensitive receptors
Definition
most tissues: skeletal muscle, adpipose..
Term
what is the general cause of hypoglycemia
Definition
low glucose causes elevated glucagon and epinepherine and low insulin
Term
what are the adrenergic symptoms of hypoglycemia
Definition
anxiety, papitation, sweating, tremor
Term
what causes the adrenergic symptoms of hypoglycemia
Definition
epinepherine, ACTH, and growth hormone release from the hypothalamus in response to decreased glucose levels
Term
what are the neuroglycopenia symptoms of hypoglycemia
Definition
headache, confusion, slurred speech, seizures, coma, death
Term
what causes the neuroglycopenia symptoms of hypoglycemia
Definition
impaired delivery of glucose to the brain
Term
what is the treatment of hypoglycemia
Definition
resolved in minutes of glucose intake
Term
what is the main worry of someone who is experiencing hypoglycemia
Definition
CNS only fuel is glucose, without glucose for too long nerves die, could cause death
Term
what does transient hypoglycemia cause
Definition
cerebral dysfunction
Term
what are the types of hypoglycemia
Definition
insulin injected, postparandial, fastine
Term
what type of patients usually have insulin injected hypoglycemia
Definition
diabetes patients
Term
what are symptoms of insulin injected hypoglycemia
Definition
unconsious, no coordiinated swallow reflex
Term
how do you treat insulin injected hypoglycemia
Definition
subcutanous or intramuscular glucagon injection
Term
what is the second most common hypoglycemia
Definition
postparandial
Term
what causes postparandial hypoglycemia
Definition
exaggerated insulin release following a meal
Term
how do you treat postparandial hypoglycemia
Definition
auto corrects itself, eat frequent small meals
Term
what is the most rare hypoglycemia
Definition
fasting
Term
what are the most serious symptoms involved in fasting hypoglycemia
Definition
neuroglycopenia
Term
what causes fasting hypoglycemia
Definition
low liver glucose production, fasting and alcohol, pancreatic tumors that make lots of insulin
Term
what are the three paths you could take to try and inhibit glucagon signaling
Definition
regulate glyconeogenesis, increase glycogen storage, decrease glycogen storage
Term
how can glycogenesis be regulated to stop glucagon signaliing
Definition
dephosphorlyate glycogen synthase
Term
how can glycogen storage be increased to stop glucagon signaliing
Definition
add insulin which decreases cAMP with phosphodiesterase and activates protein phosphatase 1. dephosphorlyate glycogen synthase to activate it
Term
how can glycogen storage be decreased to stop glucagon signaliing
Definition
glycagon and epinepherine induce cAMP production, protein kinase A phosphorlyates glycogen synthase, phosphorlyated glycogen synthase is inactivated
Term
in gulcagon signaling once the associated enzymes are phosphorlyated, what occurs in the liver
Definition
break don of glycogen and increased gluconeogenesis, ketogenesis, amino acid uptake to make carbon skeletons for gluconeogenesis
Term
in gulcagon signaling once the associated enzymes are phosphorlyated, what occurs in the adipose
Definition
activation of lipolysis, free fatty acids are used by the liver to make acetyl coenzyme A to do ketogenesis
Term
what are the steps of glucagon signaliing
Definition
1. glucagon binds glucagon receptor
2. receptor activates g-protein which activates adenylyl cyclase
3. adenylyl clcyase generates cAMP
4. protein kinase phosphorlyates and activates metabolic enzymes
Term
what are the steps of insulin signaling
Definition
1. insulin binds receptor tyrosine kinase on the insulin receptor
2. tyrosine kinase phosphorlyates beta subunit of insulin receptor and insulin receptor substrates
3. substrates promote activation of protein kinases and phosphatases
4. proteins affect gene expression, cell metabolism, and cell growth
Term
once insulin binds to the membrane, what changes occur in the membrane
Definition
insulin promotes recruitment of insulin sensitive glucose transporters in so more transporters come to the membrane and increase insulin mediated glucose uptake
Term
what changes occur in the membrane after insuliin levels are reduced
Definition
glucose transporters are taken out of the membrane and stored in the cell as endosome
Term
after signaling, what does insulin cause to happen to carbohydrate metabolism (explain what goes on in each tissue)
Definition
glycogen synthesis in the liver, increases glucose transporters in muscle (GLUT-4), in adipose it causes glycerol-3-phosphate synthesis for TAG production
Term
after signaling, what does insulin cause to happen to lipid metabolism
Definition
takes fatty acids out of the blood to increase TG synthesis in adipose, uses glucose to make glycerol-3-phosphage and FA for TAG synthesis
Term
after signaling, what does insulin cause to happen to protein metabolism
Definition
stimulates amino acid uptake by most tissues and protein synthesis
Term
How do beta cells sense changes in glucose levels, explain the process
Definition
Sugar is phosphorlyated by glucokinase and converted to ATP, the increase in ATP closes K channels, depolarizing the membrane, calcium voltage gated ion channels open, calcium flows in, fusion and secretion of insulin granules that are inside the cell
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