Term
| What is the storage form of glucose? |
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Definition
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Term
| Where is glycogen primarily synthesized? |
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Definition
| liver(highest concentration) and muscle(greatest amount overall) |
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Term
| Muscle uses glycogen for? |
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Definition
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Term
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Definition
| raising blood glucose levels in response to glucagon |
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Term
| Glycogen synthesis will occur in direct response to? |
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Definition
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Term
| Why are the branches in glycogen, a(1,6), so important? |
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Definition
-They increase the overall solubility of glycogen.(W/o direct damage to our muscle and liver will occur.)
-Allow for rapid synthesis and degradation |
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Term
| What side are glucose residues added to? |
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Definition
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Term
| Muscle has no glucagon receptors, so it has no response to its release. Does muscle,however, respond to insulin release? |
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Definition
| Yes, it responds by taking glucose from the blood and it will also synthesize glucagon under these conditions. |
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Term
| What two enzymes degrade glycogen? |
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Definition
1) glycogen phosphorylase (only can work up to 4 residues away from a branch point)
2) debranching enzyme |
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Term
| What two enzymes synthesize glycogen? |
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Definition
1) glycogen synthase
2) branching enzyme |
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Term
| What enzyme regulates glycogen phosphorylase activity? |
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Definition
| (Glycogen) Phosphorylase kinase |
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Term
| What are the regulatory enzymes of importance to glycogen metabolism? |
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Definition
1) Glycogen Phosphorylase Kinase
2) cAMP dependent protein kinase
3) Protein phosphatase I- dephosphorylates proteins
4) Protein Inhibitor- regulates the phosphatase |
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Term
| What enzyme uses ATP to make G6P from glucose? |
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Definition
| hexokinase or glucokinase |
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Term
| What enzyme is reversible and can make Glucose-1-Phosphate from G6P? |
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Definition
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Term
| What enzyme does the irreversible reaction of making UDPG from G1P? |
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Definition
UDP-Glucose Pyrophosphorylase
Or glucose 1-phosphate
uridylyltransferae |
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Term
| Where do the phosphates comes from in UDPG? |
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Definition
| One phosphate in UDP-glucose is from G-1-P; the other is the a phosphate of UTP. |
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Term
| What is the role of glycogenin? |
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Definition
-It is the initiator of glycogen synthesis.
-Glycogen Initiator Synthetase, an activity of glycogenin adds the first six glucose residues to itself (glycogenin). Glycogen synthase and branching enzyme can then use this as a primer to fully synthesize glycogen. |
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Term
| How much ATP is required to add a glucose residue starting from glucose to an existing glycogen chain. |
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Definition
| 2 ATP or 1 ATP if you start from G6P |
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Term
| What cofactor does Glycogen Phosphorylase require? |
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Definition
| Vit B6 aka pyridoxal phosphate |
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Term
| What adds one glucose residue from UDP-glu to non-reducing end of existing glycogen chain? |
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Definition
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Term
| What transfers residues from one chain to create an a (1,6) bond and a new non-reducing end. Increases glycogen solubility and enzyme access rate to the ends? |
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Definition
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Term
| What degrades glycogen at non-reducing ends one residue at a time via a phosphorolysis reaction? Will only work up to four residues of a branch point. |
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Definition
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Term
| What removes 3 glucosyl residues from a non-reducing end and adds to another chain? Removes a (1,6) linkages by a hydrolysis reaction. |
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Definition
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Term
| cAMP Dependent Protein Kinase does what in terms of glycogen metabolism? |
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Definition
It Phosphorylates both
1) Glycogen synthase- goes from a/I(active to b/D(inactive
2) Phosphorylase Kinase- goes from inactive to active form
then this phosphorylates- Phosphorylase(inactive) b to Phosphorylase a(active) |
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Term
| What can active Glycogen Synthase after it has been phosphorylated and this inactivated? |
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Definition
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Term
| What can allosterically activate Glycogen Synthase D? |
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Definition
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Term
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Definition
1) Glycogen Synthase D- activates
2) UDP-glucose D form (decreases Km and Vmax)-activates
3) Hexokinase- inactivates |
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Term
| What inhibits Phosphorylase a(active) in the liver and muscle? |
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Definition
Phosphorylase(liver)- Glucose
Phosphorylase(muscle)- Creatine-phosphate |
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Term
| Thus Phosphorylase b in the liver have any allosteric modifiers? If yes what? |
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Definition
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Term
| Thus Phosphorylase b in the muscle have any allosteric modifiers? If yes what? |
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Definition
Activator- AMP
Inhibitor- ATP, G6P |
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Term
| Phosphorylase kinase which is activated by PKA, also can be activated partially by what? |
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Definition
| Ca2+ (it binds to the delta subunit) |
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Term
| What is the delta subunit in Phosphorylase Kinase also called? |
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Definition
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Term
| What regulates Protein Phosphatase I? And what activates this? |
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Definition
| Protein phosphatase inhibitor I- regulated by PKA(activated via phosphorylation)- when activated it binds to and blocks Protein Phosphatase I |
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Term
| What else regulates Phosphtase I? |
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Definition
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Term
| What happens when glucagon is released? |
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Definition
1) Glucagon binds to receptors on the cell
2) Gs activated, binds GTP
3) Adenylate cyclase activated, cAMP levels increase, the cascade is initiated
4) PKA(cAMP dependent protein kinase activity increases)
5) Phosphorylase kinase is phosphorylated and activated
6) Protein inhibitor-1 phosphorylated, activated, and binds to protein phosphatase 1 to block phosphatase activity
7) Phosphorylase kinase activates phosphorylase, converting it from the b to the a form
8) Phosphorylase a converts glycogen to G-1-P, which is isomerized(by Phosphoglucomutase) to G-6-P, and then exported as glucose
9) Glucose is exported because glycogen synthase has been phosphorylated and inactivated by the cAMP dependent protein kinase (or phosphorylase kinase, or a calcium activated kinase)
10) As G-6-P levels increase, G6Pase produces glucose, which is in levels below the Km for glucokinase, so rephosphorylation does not occur
11) Protein kinase A has also inhibited PFK-2 and PK in the liver, stopping glycolysis
12) This aids liver glucose export |
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Term
| Epinephrine has two receptors alpha and Beta, when it binds to this receptor the same cascade occurs as when glucagon binds? |
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Definition
| Beta receptor for epinephrine |
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Term
| What happen epinephrine binds to the alpha receptor? |
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Definition
1) Generates second messengers based on phosphatidylinositol
a- Diacylglycerol(DAG) and IP3 are released
b- DAG activated Protein Kinase C
c- IP3 stimulates calcium entry into the hepatocyte
2) The calcium binds to, and activates, phosphorylase kinase (also another calcium dependant kinase, via calmodulin)
3) PKC also phosphorylates, and inactivates, glycogen synthase |
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Term
Glycogen Storage Disease: Type 0
What is lacking and what are the symptoms? |
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Definition
Lacks: liver glycogen synthase
Symptoms: Fasting hypoglycemia. Liver has very low, if any, glycogen.
Treatment- frequent small meals |
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Term
Glycogen Storage Disease: Type I (von Gierke's disease)
What is lacking and what are the symptoms? |
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Definition
Lacks- glucose-6-phosphatase
Symptoms- Enlargement of liver, severe hypoglycemia. Increased glycogen in liver, of a normal structure.
Treatment- frequent small meals |
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Term
| Type I Glycogen Storage Disorder is also known as? |
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Definition
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Term
Glycogen Storage Disease: Type IV (Anderson's disease)
What is lacking and what are the symptoms? |
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Definition
Lacks- branching enzyme
Symptoms- Fatal disease. Liver has low levels of non-branched glycogen, which presents solubility problems. Cirrhosis develops.
Treatment- liver transplant |
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Term
| Type IV Glycogen Storage Disease is also known as |
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Definition
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Term
Glycogen Storage Disease: Type V (McArdle's disease)
What is lacking and what are the symptoms? |
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Definition
Lacks- muscle phosphorylase
Symptoms- Weakness and cramping after exercise; inability to use muscle glycogen as energy source.
Treatment- pt can still makes ATP from fatty acids, more of an inconvenience |
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Term
| Type V Glycogen Storage Disease is also called? |
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Definition
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Term
| What does MODY stand for? |
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Definition
| Maturity onset diabetes of the young |
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Term
| How do you get MODY and what problems are associated with it? |
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Definition
-Inheritable(in one case, mapped to glucokinase/other case transcription factors are mutated)
- Glucokinase is only expressed in liver and pancreatic B-cels
-Normally B-cells release insulin in response to glucose
-MODY pt doesn't release insulin properly
-this suggests that a metabolite of glucose signals the b-cell to release insulin, since glucokinase is the defective enzyme |
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Term
| What makes Glucokinase an effective glucose sensor for the pancreatic B-cells as apposed to Hexokinase? |
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Definition
Glucokinase has a higher Km than Hexokinase, so it will only work when glucose levels are high
Hexokinase with its lower Km will always be sensitive to glucose even low levels |
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Term
| What drug is given to type II diabetics? They bind to and close the potassium channels on the surface of the beta cells. This increases calcium movement into the beta cell, leading to insulin release. |
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Definition
| Sulfonylurea-based drugs (Glipizide) |
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Term
| What is the critical metabolite for releasing insulin from the B-cell? |
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Definition
| ATP (it inhibits the K+ channel/ Ca2+ keeps flowing in and then once a critical level is hit- insulin goes out) |
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Term
What is the influence of these factors on insulin release?
1) glucose
2) amino acids
3) neural input
4) gut hormones
5) epinephrine |
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Definition
1) positive
2) minor- positive
3) minor- positive
4) minor- positive
5) negative |
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Term
| Are neural signals(vagus nerve) required for insulin release? |
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Definition
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Term
| What released after food ingestion also stimulates insulin release(minor)? |
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Definition
| Gastric Inhibitory Peptide |
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Term
| Does a MODY pt develop the same longterm problems that a Type I diabetic has? |
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Definition
| No, because insulin is still being produced, GK has been altered and is not making G6P as well and not enough ATP to stimulate proper release of insulin. |
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