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60 Cards in this Set
- Front
- Back
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How does a cell trap glucose?
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phosphorylates the glucose molecule within the cell
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what enzymes are used to trap glucose inside the cell?
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Enzymes in the LIver & Pancreas: Glucokinase
Most other cells use: Hexokinase |
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What enzyme does the brain and kidney use to trap glucose?
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Hexokinase I
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what enzyme does skeletal muscle use to trap glucose in the cell?
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Hexokinase II
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what enzyme does the spleen, lymphocytes, and fetal development use to trap glucose within the cell?
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Hexokinase III
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how is the process of trapping glucose inside the cell regulated?
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both competitive and allosteric regulation through product feedback (the phosphorylated G6P is the product)
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what regulates the process of trapping glucose in the cells of the pancreas and the liver?
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There is no feedback inhibition
Fructose-6-phosphate from glycolysis can regulate Also Glucokinase Reg Protein (GKRPT) can regulate Glucokinase |
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What can be done with glucose-6-phosphate?
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can be used to form:
Glycogen (Storage) Pyruvate (ATP production) Ribose-5-Phosphate (for DNA/RNA) |
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True or False
Glucose-6-Phosphate is one of the three key junction metabolites |
True
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what is a key junction metabolite?
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a key junction metabolite is something that a cell can process many different ways to get many different products
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What is glycolysis?
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Pathway of breakdown of glucose and yields energy and pyruvate
the free energy is used to form ATP and NADH |
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Where does glycolysis occur?
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in the cytoplasm of cells
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What cells have the glycolysis pathway and what does this pathway do?
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Every cell in the body
breakdown glucose |
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What are the two phases of glycolysis?
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Phase 1: Energy investment phase (5 steps)
Phase 2: Energy yielding phase (5 steps) |
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Describe what is happening in Phase 1 on glycolysis
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Energy investment phase
- 1 ATP is used to trap glucose - 2 ATP used to split glucose into 2-three carbon molecule |
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Describe what is happening in Phase 2 of glycolysis
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Energy Yielding Phase
- 0 ATP used, 4 ATP Produced - 2 NADH produced - Final product of PYRUVATE |
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what is the 2,3 BPG shunt and why is it important?
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Pathway that takes 15-25% of glucose being metabolized and shunts it out of glycolysis and uses 2,3 BPG Mutase to convert it.
It is important because 2,3 BPG acts to bind hemoglobin to help offload oxygen |
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what is the net yield of ATP for anaerobic glycolysis?
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2 ATP
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what is the net yield of ATP for Aerobic glycolysis?
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6-8 ATP
(2 direct ATP, 4-6 ATP from electrons on NADH) |
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what is substrate level phosphorylation?
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using glycolysis to generate sudden burst of ATP without oxygen by using glucose and glycogen to form ATP and lactate acid.
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what two enzymes in glycolysis perform substrate level phosphorylation?
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Phosphoglycerate kinase
Pyruvate kinase |
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what two high energy compounds are used by Phosphoglycerate kinase/pyruvate kinase to form ATP?
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1,2 bisphosphoglycerate
Phosphoenolpyruvate |
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what can be done with pyruvic acid (pyruvate)?
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form:
ethanol (anaerobic in yeast) Acetyl-CoA (aerobic) Lactate (anaerobic in humans) Oxaloacetic acid (needed in TCA cycle) |
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what is an isoenzyme?
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enzymes that differ in amino acid sequence but catalyze the same chemical reactions
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what enzyme forms lactic acid?
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Lactate Dehydrogenase
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How many different isoenzymes are there of Lactate Dehydrogenase?
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5
LDH1: HHHH LDH2: HHHM LDH3: HHMM LDH4: HMMM LDH5: MMMM |
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how is the activity of Lactate dehydrogenase regulated?
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product of glycolysis "Fructose-6-bisphosphate" which is formed by the rate limiting step of glycolysis and oxygen play a role
If F-1,6-BPH is high and Oxygen is low > acid If both are high, oxygen will inhibit Lactate dehydrogenase |
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What is lactic acidosis?
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excess lactic acid which inturn causes metabolic acidosis
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what causes lactic acidosis?
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renal failure, ketoacidosis, liver failure, low oxygen, salicylates
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how does the anion gap help with differential diagnosis of lactic acidosis?
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formula of the difference between sodium concentration and the sum of bicarb and Chlorine levels
- if Anion Gap is = 12 +/- 2 > NORMAL |
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how do you treat a patient with lactic acidosis?
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giving the patient bicarbonate (not so good) and experimental agent Carbicarb
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how is fructose fed into glycolysis?
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can be converted into glucose, triglycerides, or lactic acid.
can be phosphorylated and fed into glycolysis after the rate limiting step Trapping enzyme: Fructokinase & Hexokinase |
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how is galactose fed into glycolysis?
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Galactose is typically converted to glucose by named enzymes and sent into glycolysis
Trapping enzyme: Galactokinase & hexokinase |
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how is mannose fed into glycolysis?
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Mannose is converted to M6P which is an epimer of glucose
Phosphomannose isomerase converts M6P into F6P and then is inserted into glycolysis after the rate limiting step Trapping enzyme: Hexokinase Conversion: Phosphomannaose iosmerase |
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What is fructose intolerance?
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Fructose intolerance is when fructose reaches toxic levels and becomes damaging to the liver
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what is the hereditary fructose intolerance?
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defect in aldolase B
any level of fructose can be damaging and must be avoided Mutation in Glut-5 which uptakes fructose in gut, causing malabsorption of Fructose |
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how often does fructose intolerance occur
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1/20,000 for hereditary FI
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Why does fructose intolerance occur?
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Accumulation of Fructose-1-PHosphate damages the liver and is toxic
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what are the signs and symptoms of Fructose intolerance? treatment?
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liver damage and avoidance of fructose
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What is galactosemia?
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hereditary disorder involving galactokinase, galactose-1-phosphate uridylytransferase, or UDP galactose-4-epimerase enzymes
Leads to an accumulation of galactose causing galacitol build-up Leads to tissue damage in eyes and the brain and liver |
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how often does galactosemia occur?
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1/40,000-60,000
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what problems does galactosemia cause and how is it treated?
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presents first weeks after birth
poor feeding weight loss vomit lethargy Hepatosplenomegaly renal tubular disease Jaundiced Treatment: eliminate lactase from the diet |
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what is the rate limiting step of glycolysis?
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the step converting Fructose-6-Phosphate to Fructose-1,6-Biphosphate
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what is the rate limiting enzyme of the rate limiting step of glycolysis?
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Phosphofructokinase-1 catalyzes the conversion of Fructose-6-Phosphate to Fructose-1,6-Biphosphate
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How does CITRATE regulate glycolysis?
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Citrate is an allosteric inhibitor of PFK-1 enzyme
This is the enzyme that catalyzes the rate limiting step of glycolysis |
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why is citrate important in the fasting state?
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1. LIver: Citrate shuttle to cytoplasm and inhibits fatty acid synthesis and glycolysis
2. LIver uses fatty acids for energy in fasting state Liver Doesn't need Glycolysis -Other tissues Citrate inhibits glycolysis in peripheral tissues to allow more blood glucose for the brain |
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why is citrate important in the feeding state?
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In the feeding state a large amount of material is going through glycolysis producing excess citrate which must be rid of to prevent negative feedback
-insulin increases Citrate Lysase levels -Citrate Lyase can cleave citrate to form Acetyl CoA to feed into Fatty acid synthesis and Cholesterol synthesis |
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what tissues have fructose 1,6 bisphosphate activity?
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Primarily the Kidneys and LIver
Also found in the muscle, intestines, and lung tissue |
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why is the presence of Fructose 1,6 bisphosphate important in the kidneys, liver, intestines, muscle, and lung tissue?
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Converts fructose 1,6 bisphosphate back to fructose 6 phosphate (reversing the rate limiting step of glycolysis)
Allows for GLUCONEOGENESIS |
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Why are there two different phosphofructokinase enzymes?
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They have the same substrate but produce different products
PFK-1: rate limiting step in glycolysis PFK-2: forms fructose-2,6-bisphosphate which regulates glycolysis via hormone control |
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Is PFK-2 found in glycolysis?
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NO
PFK 2 forms fructose 2,6 bisphosphate which regulates glycolysis via hormone control |
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How is PFK-1 regulated?
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Stimulated:
1. AMP: low energy state stimulates 2. Fructose 2,6 bisphosphate: intercellular signaling Inhibitory: 1. ATP: high energy state inhibits 2. Citrate: slow glycolysis to slow pyruvate movement into TCA cycle |
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Why is there completely different effect of Epinephrine on PFK-2 in heart muscle vs. liver tissue?
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Liver: Epinephrine increases cAMP activity > Phosphorylates PFK-2 Phosphatase enzyme > Less F-2,6-BP
Heart: Epinephrine increases cAMP activity > phosphorylates PFK-2 Kinase > More F-2,6-BP different isoenzymes of PFK-2 in different tissues since the heart is a consumer > Epinephrine increases glycolysis LIver functions in Gluconeogenesis so Epinephrine inhibits |
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How is PFK-2 regulated?
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PFK-2 has a kinase and a phosphatase
Agents that regulate it are: 1. Insulin 2. Glucagon 3. Fructose-6-Phosphate |
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How does insulin affect PFK-2
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super charges glycolysis by dephosphorylating PFK-2 putting it into the active Kinase stage to signal to increase glycolysis
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how does glucagon affect PFK-2
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slows glycolysis by phosphorylating the PFK-2, activating the phosphatase, to slow glycolysis
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how does fructose-6-phosphate affect PFK-2
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stimulates Phosphoprotein phosphatase to activate PFK-2 Kinase and deactivate PFK-2 phosphatase causing a feed forward stimulation to promote increased rate of PFK-1 which increases glycolysis
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How is pyruvate kinase regulated?
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THIS IS THE LAST REGULATED ENZYME IN GLYCOLYSIS
1. Insulin: stimulates > puts PK into a more active unphosphorylated state 2. Glucagon: inhibits > promotes cAMP-dependent kinase to phosphorylate PK making it LESS active 3. F-1,6-BP: stimulates (allosteric activator) 4. Acetyl-CoA: inhibits (allosteric inhibitor) 5. ATP: inhibits (allosteric inhibitor) 6. Alanine: inhibits (allosteric inhibitor) |
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How does insulin increase the level of enzymes that are involved in glycolysis and what enzymes are involved?
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Insulin changes the level of protein factors which act as transcription factors for specific DNA sequences to modify certain protein populations
Some specific transcription factors: Forkhead Transcription Factor, Sterol response element binding protein, Carbohydrate response element binding protein Insulin raises: 1. Hexokinase II in muscle 2. Hexokinase IV in LIver 3. PFK-2 levels increase (regulate glycolysis via hormone control) 4. Pyruvate kinase levels increase |
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How does glucose increase the level of pyruvate kinase?
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1. glucose increases the level of xyulose-5-phosphate
2. X-5-P regulates the PFK-2 activity and also a phosphoprotein phosphatase to remove phosphate from ChREBP so it can bind to DNA 3. ChREBP binds the DNA to activate the Pyruvate Kinase protein production |
