Term
| What are the major metabolic roles of glycolysis (4)? |
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Definition
1) Entry point of carbohydrates into metabolism
2) Generate energy (ATP) from carbohydrates
3) Supply precursors for amino acid, large lipids, and purine/pyrimidine biosynthesis
4) In times of energy excess, generate precursors for fat and glycogen biosynthesis (the energy storage molecules) |
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Term
| What is the role of glycolysis in the muscle? |
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Definition
| use energy from glycolysis to do work (contraction); generate energy in absence of oxygen |
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Term
| What is the role of glycolysis in the liver? |
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Definition
| Use carbons and energy from carbohydrates to make fat, serum proteins, and other biosynthetic precursors |
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Term
| The Hexokinase reaction- (tell me the details) |
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Definition
Takes glucose and ATP and make glucose-6-phosphate and ADP
1. Group Transfer Reaction
2. Irreversible (energy loss as ATP is hydrolyzed)
3. “Activate” glucose
4. Trap glucose inside the cell as G6P |
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Term
| The Phosphofructokinase-1 Reaction- Tell me the details |
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Definition
Takes Fructose-6-Phosphate and ATP and get Fructose-1,6-bisphosphate and ADP
1. Second activation step, lose energy
2. Mechanism same as HK step
3. Major regulated step of glycolysis
4. Sugars are now committed to the
glycolytic pathway |
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Term
| Refers to the same functional group on different atoms within the same molecule (F 1,6 BP) |
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Definition
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Term
| Refers to two of the same functional groups attached to the same atom of a molecule, or linked together and attached to just one atom of the molecule (ie ADP, has the two phosphates attached to each other, which are then linked to the 5’-carbon of ribose) |
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Definition
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Term
| Which step generates a high energy bond? |
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Definition
Its when G3P (Glyceraldehyde-3-Phosphate) and NAD+ are transformed by Glyceraldehyde-3-phosphate Dehydrogenase to 1,3 BPG (1,3 Bisphosphoglycerate and NADH
1. Carbon 1 of G3P is oxidized (aldehyde to acid)
2. NAD+ is reduced (gains a proton and two electrons to form NADH)
3. The formation of a phospho-anhydride bond generates a high energy bond
4. The enzyme requires an active sulfhydral group |
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Term
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Definition
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Term
| The phosphoglycerate kinase reaction- tell me the details |
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Definition
1,3 BPG and ADP are made into 3PG and ATP
1. Phosphoryl group transfer, and the high energy of the phospho-anhydride bond is conserved as a high energy bond of ATP
2. Reversible reaction; substrate-level phosphorylation
3. Since 1 glucose gives rise to 2 molecules of 1,3 BPG, this step generates 2 ATP molecules per glucose, but the overall yield of glycolysis is zero at this point (due to the two activation steps). |
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Term
| What are the three irreversible steps in glycolysis? |
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Definition
1) Hexokinase (Glucokinase in liver and pancreas)- Glucose + ATP yield G6P +ADP
2) PFK-1 -F6P + ATP yield F1,6BP + ADP
3) Pyruvate Kinase- PEP + ADP yields pyruvate + ATP |
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Term
| What is unique about the three key steps? |
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Definition
| All of these steps involve large energy changes as the reactant is converted to the product. Others steps use ATP or other high energy substances such as NADH, but these are not reversible. |
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Term
| What is the major regulatory enzyme of glycolysis? |
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Definition
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Term
| If energy levels are high, and there is an adequate supply of carbon skeletons, glycolysis is? |
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Definition
| inhibited (use glucose to store energy as glycogen or fat) at least this is what should happen, certain disease can change this |
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Term
| What are the inhibitors of PFK-1? |
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Definition
ATP-high energy available; it is also a substrate for the reaction
Citrate-from the Krebs tricarboxylic acid cycle, and signifies adequate carbon skeletons for biosynthesis |
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Term
| What are the activators of PFK-1? |
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Definition
1) Fructose-2,6-Bisphosphate- which links the regulation of glycolysis to hormonal signals (in the liver only)
2) AMP- indicating low energy levels |
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Term
| Why AMP as an indicator of low energy levels? |
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Definition
| The ratio of [AMP]/[ATP] increases more rapidly than the [ADP]/[ATP] ratio |
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Term
What are some of the enzymes that do this reaction...
2 ADP-->ATP +AMP |
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Definition
1) myokinase( aka adenylate kinase)- found in the muscle, hence the myo-
extra-credit info -
Two ADK isozymes have been identified in mammalian cells. These specifically bind AMP and favor binding to ATP over other nucleotide triphosphates (AK1 is cytosolic and AK2 is located in the mitochondria). A third ADK has been identified in bovine heart and human cells,[3] this is a mitochondrial GTP:AMP phosphotransferase, also specific for the phosphorylation of AMP, but can only use GTP or ITP as a substrate |
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Term
| So an increase in ADP which leads to a ____ ADP to ATP ratio is proportional to an AMP to ATP ratio of ____ |
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Definition
ADP to ATP 2:1
AMP to ATP 4:1 |
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Term
| The rate of which a product of a reaction is formed? |
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Definition
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Term
| How is F2,6BP an activator for glycolysis? |
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Definition
| reduces substrate concentration required for the enzyme to reach one-half maximal velocity. The maximal velocity does not change, but the amount of substrate required to reach that velocity is decreased (look at slide 15 for pictures to clarify) |
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Term
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Definition
It is regulated by hormones(epinephrine and glucagon). They bind to the outside of the cell and active cAMP. cAMP with a cAMP dependent protein kinase will phosphorylate PFK-2 with ATP, resulting in an inactive PFK-2-P.
As a result, liver will stop using glucose so glucose can be exported. To stop the liver from using glucose, glycolysis is slowed down by reducing F-2,6-BP levels, which reduces PFK-1 activity (liver specific in response to glucagon |
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Term
| When epinephrine and glucagon (hormones) are present will muscle stop using glucose? |
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Definition
| No, skeletal muscle PFK-2 is not phosphorylated (different isozyme – but heart is an exception) |
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Term
| PFK-2 is a bifunctional enzyme, what two activities does it do? |
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Definition
1) It contains a kinase which produces Fructose-2,6-Bisphosphate
2) It contains a phosphatase activity which converts F2,6 BP to F6P and P |
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Term
| When PFK-2 is phosphorylated, what happens? |
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Definition
| The phosphotase activity is activated and the kinase activity is inhibited (this only happens in the liver) |
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Term
| What is one of the main jobs of the liver? |
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Definition
| export glucose when blood glucose levels drop |
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Term
| What is the main job of skeletal muscles? |
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Definition
| to do work, using glucose or fat for energy |
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Term
| Why is the Hexokinase or Glucokinase reaction so important? |
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Definition
| traps glucose inside the cell as G6P |
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Term
| In the liver: When blood glucose levels drop _______ is released, the ______ cascade is activated, ______ is phosphorylated, _____ less active, ________ is slowed, and glucose export can occur |
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Definition
glucagon
cAMP
PFK-2
PFK-1
glycolysis |
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Term
| Is PFK-2 phosphorylated in the muscle when glucagon is released? |
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Definition
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Term
| What will phosphorylate PFK-2 in the heart? |
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Definition
1) insulin-stimulated protein kinase (protein kinase B)
2) an AMP-activated protein kinase |
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Term
| When PFK-2 in the HEART is phosphorylared, what activity is occurring? |
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Definition
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Term
| Why is the strange PFK-2 for the heart so important? |
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Definition
| Glycolysis can still occur in the heart under low energy conditions (high AMP) and also when glucose levels are high (insulin release) |
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Term
| What is an inhibitor of Hexokinase(muscle)? |
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Definition
| increasing levels of G6P(feedback inhibition) |
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Term
| Is Glucokinase inhibited by G6P? |
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Definition
| No, this is because under conditions of high levels GK will be active and can force liver glycolysis to proceed in order to store energy as fat |
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Term
| What are the three forms of Pyruvate Kinase? |
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Definition
L (liver)
M (muscle)
A (other) |
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Term
| What reaction does Pyruvate Kinase do? |
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Definition
PEP + ADP to Pyruvate + ATP
...this rxn is not spontaneous |
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Term
| Liver Pyruvate Kinase is activated by... |
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Definition
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Term
| Liver Pyruvate Kinase is inhibited by... |
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Definition
1) ATP
2) alanine
3) it can also be phosphorylate by cAMP dependent protein kinase-this inhibiting its activity |
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Term
| Increase levels of cAMP cause what to happen in the liver? |
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Definition
| switches to glucose export and glucose production via gluconeogenesis |
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Term
| Allosteric controls of glycolysis is related to what state of the cell? |
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Definition
| Energy State, hence all that ATP and AMP and other precursors |
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Term
| Covalent modification (phosphorylation) is linked to? |
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Definition
| hormonal signals- epinephrine, glucagon, insulin- these monitor blood glucose levels |
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Term
When blood glucose levels are low, the liver...
When blood glucose levels are low, the skeletal muscles... |
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Definition
in the liver- supply other tissues with glucose
in the muscle- use glucose from own stores or from the blood |
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Term
In the liver when blood glucose levels are high-
In the muscle, when blood glucose levels are high- |
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Definition
liver- convert excess glucose to energy storage form
muscle- store glucose as glycogen in the muscle |
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Term
| Which cycle forms lactate in the muscle regenerates NAD+, which allows glycolysis to continue? |
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Definition
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Term
| What can we do with lactate? |
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Definition
| send it to the liver, it can be used for glucose production |
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Term
| What competes with substrate for binding to the active site? |
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Definition
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Term
| What binds to a site distinct from the substrate binding site and induces conformational change, which reduces enzyme activity? |
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Definition
| non-competitive inhibitor |
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Term
| What enzyme deals with fructose? |
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Definition
| fructokinase, active in the liver uses ATP to make F1P |
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Term
| What are the assumptions of enzyme kinetics analyses? |
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Definition
1) The production of product is linear with time during the time interval used.
2) The concentration of substrate vastly exceeds the concentration of enzyme. This means that the free concentration of substrate is very close to the concentration you added, and that substrate concentration is constant throughout the assay.
3) A single enzyme forms the product.
4) There is negligible spontaneous creation of product without enzyme
5) No cooperativity. Binding of substrate to one enzyme binding site doesn't influence the affinity or activity of an adjacent site.
6) Neither substrate nor product acts as an allosteric modulator to alter the enzyme velocity. |
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Term
What enzyme does this rxn:
Fructose + ATP -->F-1-P + ADP |
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Definition
| Fructokinase- this rxn happens very quickly, so a if you have too much fructose, such as in an IV you will cause a lot of problems |
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Term
What enzyme does this rxn:
F-1-P ---> DHAP + Glyceraldehyde |
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Definition
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Term
What enzyme does this rxn:
Glyceraldehyde + ATP --> G3P + ADP |
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Definition
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Term
What enzyme does this rxn:
DHAP --> G3P |
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Definition
| TPI (Triose Phosphate Isomerase) |
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Term
| Can HK phosphorylate Fructose in addition to Glucose? |
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Definition
| Yes, but rarely see since the Km is so high. |
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Term
| Hereditary fructose intolerance is caused by a defect in what? |
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Definition
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Term
| Increases in F1P results in? |
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Definition
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Term
| Galactose after going through some changes will enter into Glycolysis as and after having used how many ATP? |
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Definition
| Galactose will enter as G6P, after having used 1 ATP (just skips the Hexokinase or Glucokinase step) |
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Term
Elevated levels of galactose in the blood is called?
And in the urine it is called? |
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Definition
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Term
Classic type galactosemia results from an inactive?
What are some of the problems associated with this? |
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Definition
Lack of Gal-1P uridylyl transferase
Have an accumulation of galactose and its alchohol form galactitol, which leads to cataract formation and irreversible mental retardation.
Also hypoglycemia also results from from galactose-1-phosphate inhibition of phosphoglucomutase |
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Term
Non-classical galactosemia results from?
And causes what problems? |
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Definition
Loss of galactokinase
Cataract formation results from galactitol formation, but no mental retardation or hypoglycemia |
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Term
| What is present in many tissues; in seminal vesicles it leads to the production of fructose for sperm motility? Its function is other tissues is not as clear. |
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Definition
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Term
| In the lens of the eye, aldose reductase will... |
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Definition
| glucose to sorbitol and galactose to galactitol |
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Term
| If sorbitol(diabetes) or galactitol(galactosemia) accumulates, then? |
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Definition
| cataracts will result from the osmotic imbalance which is created as these sugar alcohols accumulate within the lens, as well as non-enzymatic glycosylation of lens proteins |
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Term
| Tell me more about starch (single chained), what are the subunits and what type of bonds? |
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Definition
| Made from repeating units of glucose aka amylose, alpha (1,4) bonds |
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Term
| Tell me more about starch(branch chained), what are the subunits and what type of bonds? |
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Definition
| When branched it forms alpha 1,4 linkages in addition to alpha 1,6 linkages, this unit is called amylopectin |
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Term
| Tell me more about lactose, what are the subunits and what type of bonds? |
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Definition
| disaccharide made from galactose Beta (1,4) glucose |
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Term
| Tell me more about sucrose, what are the subunits and what type of bonds? |
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Definition
| It is a disaccharide made from glucose alpa(1,2) fructose |
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Term
| Digestion of the starch begins where and with what and what is created? |
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Definition
| Starch digestion begins in the mouth with salivary amylase, which is a endoglycosidase, which cleaves internal a (1,4) bonds forming dextrins |
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Term
| What neutralizes the acidity in the intestine? |
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Definition
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Term
| What enzyme degrades starch in the intestine? |
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Definition
pancreatic alpha-amylase
the end products are...
maltose-disaccharides with alpha (1,4) bonds
isomaltose- disaccharides with alpha (1,6) bonds
dextrins- of 6-8 residues, with both types of bonds |
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Term
| What four enzymes are found on the brush border membranes of intestinal epithelial cells? |
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Definition
1) sucrase-maltase
2) glucoamylase complex
3) lasctase, or Beta-glcosidase
4) Trehalase |
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Term
| What does sucrase-isomaltase hydrolyze? (3 things) |
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Definition
1) maltose (a 1,4)
2) isomaltose (a 1,6)
3) sucrose (glu a 1,2 fructose) |
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Term
| What does glucoamylase complex do? |
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Definition
| It is a exoglycosidase for a(1,4) bonds (maltose, dextrins) |
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Term
| Combination of what two enzymes will hydrolyze starch to glucose? |
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Definition
| sucrase-isomaltase and glucoamylase complex |
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Term
| What is specific for the gal beta (1,4) glu bond found in lactose? |
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Definition
| lactase or Beta-glycosidase |
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Term
| What cleaves glucose alpha (1,1) glucose? Its found in muschrooms. |
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Definition
| Trehalase it cleaves trehalose |
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Term
| In the intestinal lumen, what two type of transporters are found there and what do they transport? |
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Definition
Facilitative transporter- fructose and glucose
Na-Glucose Transporter- glucose and galactose |
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Term
| What forces glycolysis forward, liver makes fat from glucose (due to high blood glucose levels; non-alcoholic steatohepatitis- NASH)? |
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Definition
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Term
| When liver only sees glucagon, it will only digest fat, if this happens for too long? |
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Definition
| You will get a fatty liver |
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Term
| What two reactions are required to reverse the PK (Pyruvate Kinase) rxn? |
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Definition
| Pyruvate Carboxylase and PEP Carboxykinase |
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Term
| What rxn does Pyruvate Carboxylase do? |
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Definition
| Pyruvate + ATP + CO2 (w/Biotin) --> Oxaloacetate + ADP, Pi |
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Term
| What rxn does PEP Carboxykinase do? |
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Definition
| Oxaloacetate + GTP --> PEP + CO2 + GDP |
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Term
| What reaction reverses PFK-1 (Phosphofructokinase-1)? |
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Definition
| Fructose 1,6 Bisphosphatase takes F1,6BP and makes F6P +Pi |
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Term
| What reaction reverses Glucokinase? |
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Definition
| Glucose-6-Phosphatase takes G6P and makes Glucose (only found in the liver and kidney) |
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Term
| The 4 major enzymes of gluconeogenesis aresplit between the matrix and cytoplasm, where will I find which ones? |
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Definition
Mitochondria matrix- Pyruvate Carboxylase
Cell cytoplasm- PEP Carboxykinase, Fructose 1,6 Bisphosphatase, and Glucose-6-Bisphosphatase |
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Term
What are the activators and inhibitors of PFK-1?
What are the activators and inhibitors of Fructose 1,6 Bisphosphatase?
What does this prevent? |
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Definition
PFK-1
Activator: AMP and F2,6BP
Inhibitor: ATP and Citrate
Fructose 1,6 Bisphosphatase
Activator: ATP and citrate
Inhibitor: AMP and F2,6BP
It prevents a futile cycle. |
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Term
| When PFK-2 is dephosphorylated, what of its two rxns is active? What else should you know? |
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Definition
| Its kinase activity is active making F2,6BP and promoting glycolysis. Insulin levels are high and glucagon is low because the blood sugar levels are high. |
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Term
| When blood sugar is low, what happens? |
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Definition
1) Glucagon is released
2) cAMP increase and protein kinase A is active
3) PFK-2 is phosphorylated and the kinase activity is inactive, but the phosphatase activity is active
4) F2,6BP levels drop and PFK-1 is inactive and Fructose-1,6-Bisphosphatase is active
5) Thus gluconeogenesis is promoted in the liver |
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Term
| What are the 3 domains of a signal transductor receptor? |
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Definition
1) extracellular (hormone binding)
2) cytoplasmic ("tranduces" the signal)
3) transmembrane part |
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Term
| If the receptor is not present on the cell surface, then? |
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Definition
| a cell is not responsive to that hormone |
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Term
| Mutant receptors where the signal is always active leads to... |
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Definition
| some cancers, esp if the receptor promotes cell growth |
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Term
| The alpha part of the insulin receptor... |
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Definition
| is in the extracellular space and binds to insulin |
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Term
| The beta part of the insulin receptor... |
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Definition
| is a transmembrane protein and binds to alpha in the extracellular space and has a kinase activity in the cytoplasm |
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Term
| What holds the four segments of the insulin receptor together? |
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Definition
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Term
| What is required for insulin action to be effective? |
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Definition
| phosphorylation of the beta domain and presence of IRS-1 (Insulin Receptor Substrate) |
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Term
| The Glucagon and Epinephrine receptors are similar in that they both? |
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Definition
1) Class of receptor which span the membrane 7 times
2)Also known as “serpentine receptors”
3) No intrinsic kinase activity
4)Linked to “G” protein |
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Term
| What is a heterotrimeric protein, which is important in signal cascades? |
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Definition
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Term
| The alpha subunit binds both GDP and GTP, what does each one mean? |
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Definition
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Term
| What are the two major types of G proteins? |
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Definition
Gi- Inhibitory G protein (when activated it actively inhibits its target protein)
Gs- stimulatory G protein |
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