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Biochem Exam 2, part 2
Glycolysis and Gluconeogenesis
81
Biochemistry
Graduate
09/13/2011

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Term
Is pyruvate higher or lower in energy than glucose? Why?
Definition
Lower, because it is in a higher oxidation state
Term
What are the three functions of glycolisis?
Definition
1. Make 2 net ATP
2. Make 2 NADH
3. Make metabolites that are AA precursors
Term
How does glucose get into a cell for glycolysis?
Definition
A GLUT protein is used for facilitated diffusion
Term
Define GLUT 4
Definition
A glucose facilitated transporter that is responsible for insulin-regulated uptake of glucose into skeletal muscle and adipose tissue
Term
What three enzymes in glycolysis are irreversible and therefore regulated?
Definition
1. Hexokinase aka Glucokinase
2. Phosphofructokinase-1
3. Pyruvate kinase
Term
About how many ATP are each NADH worth?
Definition
About 2.5 ATP
Term
In what way does hexokinase irreversibly start glycolysis?
Definition
1. Once a phosphate is on glucose, it can't go back out the GLUT transporter

2. It consumes ATP to phosphorylate
Term
Define glucokinase
Definition
A form of hexokinase in the liver and β-cells of pancreas that has low affinity but high capacity
Term
How does glucokinase prevent hyperglycemia?
Definition
Because it has high capacity, it keeps up with glucose processing in the liver
Term
What effect does fructose-6-phosphate have on glucokinase, and why?
Definition
It inactivates and sequesters glucokinase, because fructose-6-phosphate is high during gluconeogenesis
Term
What does glucokinase do in β-cells of the pancreas?
Definition
It serves as a glucose sensor to help β-cells control insulin output
Term
What enzyme converts D-glucose to Glucose-6-phosphate?
Definition
Hexokinase
Term
What enzyme converts glucose-6-phosphate to fructose-6-phosphate?
Definition
Phosphoglucoseisomerase
Term
What enzyme converts fructose-6-phosphate to fructose-1,6-bisphosphate?
Definition
Phosphofruktokinase-1
Term
What enzyme regulates the most import control point/commitment step in glycolysis?
Definition
Phosphofructokinase-1
Term
Why is Phosphofructokinase-1 the most regulated and commitment step of glycolysis?
Definition
Fructose-1,6-bisphosphate is not used by other pathways
Term
What inhibits phosphofructokinase?
Definition
ATP (an energy-rich signal), citrate (a Krebs intermediate), and glucagon
Term
What activates phosphofructokinase?
Definition
AMP (allosterically), insulin (by pathway), fructose-2,6-bisphosphate
Term
Describe the pathway by which insulin activates phosphofructokinase
Definition

1. High insulin decreases cAMP, reducing protein kinase A


2. This favors dephosphorlated PFK-2/FBP-2 complex


3. This formation (activated PFK-2) favors formation of fructose 2,6-bisphosphate


4. Fructose 2,6-bisphosphate activates phosphofructokinase

Term
What enzyme converts fructose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate?
Definition
Aldolase
Term
What enzyme converts dihydroxyacetone phosphate to glyceraldehyde-3-phosphate?
Definition
Triose phosphate isomerase
Term
What enzyme converts glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate?
Definition
Glyceraldehyde-3-phosphate dehydrogenase
Term
How does Glyceraldehyde-3-phosphate dehydrogenase convert its substrate back to a diphosphate status without using ATP?
Definition
It couples the extraction of two electrons with the installation of a Pi
Term
How does arsenic poisoning inhibit glycolysis?
Definition
Arsenate enters glyceraldehyde-3-phosphate instead of a Pi, then this product is spontaneously hydrolyzed, producing 3-phosphoglycerate and bypassing substrate level ATP generation
Term
What enzyme converts 1,3-bisphosphoglycerate to 3-phosphoglycerate?
Definition
Phosphoglycerate kinase
Term
Why do red blood cells sometimes bypass phosphoglycerate kinase?
Definition
They instead use mutase to produce 2,3-bisphosphoglycerate, an allosteric regulator of hemoglobin
Term
What converts 3-phosphoglycerate to 2-phosphoglycerate?
Definition
Phosphoglycerate mutase
Term
What enzyme converts 2-phosphoglycerate to phosphoenolpyruvate?
Definition
Enolase (dehydrates to form high energy phosphoenolpyruvate)
Term
What converts phosphoenolpyruvate to pyruvate?
Definition
Pyruvate kinase
Term
What are some activators of pyruvate kinase?
Definition
Fructose-1,6-bisphosphate (feedforward regulation)

AMP
Term
What are some inhibitors of pyruvate kinase?
Definition
ATP and glucagon
Term
Where do most of the rare genetic defects of glycolytic enzymes occur?
Definition
Pyruvate kinase (PK deficiency disease)

4% in phosphoglucose isomerase
Term
Why are red blood cells in danger of hemolytic anemia?
Definition
They lack mitochondria and are thus highly dependent on glycolysis
Term
What does lactate dehydrogenase do?
Definition
Catalyzes formation of lactate from pyruvate, regenerates NAD+
Term
What can circulatory collapse cause?
Definition
Global acidosis, which can be used as a measure of O2 debt
Term
Define Cori cycle
Definition
The cycle by which lactate enters the bloodstream, is recovered by hepatocytes for gluconeogenesis, and then sent back to muscle
Term
What does pyruvate decarboxylase do?
Definition
In yeast, it anaerobically converts pyruvate to CO2 and Ethanol
Term
Why would yeast want to produce ethanol?
Definition
It may be beneficial as a poison to competitors
Term
Define fermentation
Definition
Metabolism that results in no net oxidation or reduction of the nutrient
Term
Define the Pasteur effect
Definition
In low O2, cells consume higher levels of glucose (to make up for lack of oxidative phosphorylation)
Term
Define the Warburg effect
Definition
Tumor cells have a higher glycolytic rate than normal cells
Term
How long does allosteric activation/inhibition take?
Definition
Minutes to hours
Term
How long do hormones take to work?
Definition
If they are acting transcriptionally, hours to days
Term
Would diabetes cause high or low glycolytic activity?
Definition
Low- lots of sugar to the blood, and little insulin
Term
What is the ΔG for the entire reaction of glycolysis?
Definition
About -63kJ/mol, so the reaction would take place without enzymes, just much slower
Term
How can cancer cells be analyzed using glycolysis?
Definition
Radiography can observe injected flourescently labled flouro-2-glucose that becomes visible after hexokinase
Term
What areas of the body are naturally excessively glycolytic?
Definition
Brain, kidney, and bladder
Term
In what condition do hepatocytes need to be in before gluconeogenesis can occur?
Definition
Low glucose, but high amino acids and fatty acids
Term
What enzyme(s) bypass pyruvate kinase in gluconeogenesis?
Definition
Pyruvate carboxylase and PEP-carboxykinase
Term
What enzyme bypasses PFK-1 in gluconeogenesis?
Definition
fuctose 1,6-bisphosphatase
Term
What enzyme bypasses glucokinase in gluconeogenesis?
Definition
Glucose 6-phosphatase
Term
What tissues are glucose dependent?
Definition
Brain, red blood cells, kidney medulla,s lens & cornea, testes, exercising muscle
Term
Define gluconeogenesis
Definition
Anabolic process by which glucose is produced from precursors such as pyruvate, lactate, glycerol, and α-ketoacids
Term
Where does gluconeogenesis occur?
Definition
Liver, and to a lesser extent the kidney cortex
Term
How does pyruvate carboxylase add a carbon to pyruvate?
Definition
First, pyruvate carboxylase activates CO2 by attaching it to its biotin group. Then it transfers to CO2 to pyruvate, forming oxaloacetate.
Term
What enzyme converts pyruvate to oxaloacetate?
Definition
Pyruvate carboxylase
Term
What is an activator of pyruvate carboxylase?
Definition
Acetyl CoA, since it signifies lipolysis
Term
What can happen to oxaloacetate after pyruvate carboxylase generates it?
Definition
It can be used as a TCA cycle intermediate or it can be converted to phospholenolpyruvate
Term
What enzyme converts oxaloacetate to phospholenolpyruvate?
Definition
PEP carboxykinase
Term
Where does gluconeogenesis take place in a cell?
Definition
Pyruvate to oxaloacetate takes place in the mitochondria, then oxaloacetate is converted to Malate to get into the cytosol
Term
What sort of energy investment does PEP carboxykinase require?
Definition
One GTP
Term
How does glucagon discourage phosphoenolpyruvate from a glycolytic fate?
Definition
Glucagon inactivates pyruvate kinase by causing its phosphorylation
Term
What enzyme converts fructose-1,6-bisphosphate to fructose-6-phosphate?
Definition
Fructose-1,6-bisphosphatase
Term
What are some activators of fructose 1,6-bisphosphatase?
Definition
ATP
Term
What are some inhibitors of fructose 1,6-bisphosphatase?
Definition
AMP, fructose-2,6-bisphosphate
Term
Describe the pathway by which high glucagon activates fructose-1,6-bisphosphatase
Definition

1. High glucagon causes increased cAMP and therefore increased protein kinase A


2. This leads to phosphorylation of the PFK-2/FBP-2 complex, FBP-2 is active


3. fructose 2,6-bisphosphatase production is impeded


4. fructose 2,6-bisphosphatase normally inhibits fructose-1,6-bisphosphatase, therefore F(1,6)BPase is now activated

Term
What enzyme transfers glucose-6-phosphate into the lumen of the ER?
Definition
Glucose 6-phosphate translocase
Term
What enzyme converts glucose-6-phosphate to D-glucose?
Definition
Glucose 6-phosphatase
Term
Where is glucose-6-phosphatase found?
Definition
It is compartmentalized inside the ER lumen of the liver and kidney
Term
How does D-glucose get out of the ER lumen and back into the bloodstream after gluconeogenesis?
Definition
Glucose transporters T2 (on lumen) and GLUT2 (on plasma membrane) transport it
Term
What does a deficiency of Glucose 6-phosphatase cause?
Definition
Type 1a glycogen storage disease and severe fasting hypoglycemia
Term
What is the energy cost to form a glucose from 2 pyruvates?
Definition
6 ATP equivalents, and oxidation of 2 NADH (about 5 ATP)
Term
What is the ΔG of gluconeogenesis?
Definition
-17kJ/mol (with all of the ATP expense)
Term
Describe the energy charge concept
Definition
A concept that represents availability of ATP to sustain homeostatic functions. For example, ATP can be formed from two ADPs if needed by use of adenylate kinase.
Term
Define adenylate kinase
Definition
An enzyme that forms ATP (and AMP) from 2ADPs, and vice versa with no energy change
Term
Define nucleoside diphosphate kinase
Definition
An enzyme that can introconvert various nucleoside triphosphates to create NTPs needed for their respective enzymes
Term
What products does ethanol consumption lead to?
Definition
Acetate and excess NADH
Term
How can ethanol consumption lead to hypoglycemia?
Definition
The excess NADH produced from ethanol oxidation can lead to the reduction of pyruvate and oxaloacetate, limiting their availability for gluconeogenesis
Term
How can ethanol consumption lead to lactic acidosis and hyperuricemia?
Definition
The NADH generated from ethanol oxidation can cause pyruvate to be reduced to lactate, causing lactic acidosis

Hyperuricemia can result if lactate competes with urate for kidney excretion
Term
Define Disulfram
Definition
An inhibitor of alcohol dehydrogenase, it is a "learning experience" deterrent for alcohol consumption because accumulation of acetaldehyde can lead to flushing, tachycardia, hyperventilation, nausea
Term
What enzyme catalyzes the oxidation of ethanol to acetate?
Definition
Alcohol dehydrogenase
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