Glycolysis Flashcards
*Be able to describe the process of glycolysis.
Glycolysis- process of breaking down glucose.
Converting one molecule of glucose to 2 molecules of pyruvate with generation of 2 net molecules of ATP
*What does hexokinase do?
Hexokinase- transfer phosphoryl group from ATP to glucose to form Glucose 6-phosphate (at expense of ATP)
Hexokinase- requires Mg^2+ or Mn^2+ as a cofactor, catalyzes the reaction.
Hexokinases also employ substrate-binding induced fit to minimize hydrolysis of ATP (increases specificity, decreases chance of becoming indiscriminate ATPase)
upon entering cell through specific transport protein, glucose phosphorylated into G6P.
*Understand the two stages of glycolysis and what is consumed and produced at each stage.
Stage 1: TRAPS glucose in the cell and modifies it so it can be cleaved into pair of phosphorylated 3-carbon compounds (HIGH PHOSPHORYL TRANSFER POTENTIAL), no ATP produced yet. (you used up 2 ATP). (investment)
Stage 2: Oxidizes the 3 carbon- compounds to pyruvate while generating 2 molecules of ATP (Pay off stage)
*Understand what substrate-level phosphorylation is.
Substrate-level phosphorylation- process of forming ATP from ADP through a phosphoryl donor that is a substrate with HIGIHER PHOSPHORYL TRANSFER POTENTIAL than ATP.
Ex: 1,3 Bisphosphoglycerate (Phosphate donor, with higher PTP than ATP) reactis with ADP to form 3-phosphoglycerate and ATP.
*Know where ATP is utilized and synthesized and where NADH is generated in the steps of
glycolysis.
ATP is utilized in 1st and 3rd steps of glycolysis:
-Glucose to form Glucose 6-phosphate
- Fructose 6-phosphate to form fructose 1, 6-bisphosphate.
ATP is synthesized in 2 steps
1. in 1,3 Bisphosphogylcerate to form 3-phosphogylcerate (1,3 BPG to 3PG) using phosphoglycerate kinase.
2. Phosphoenolpyruvate to form pyruvate (through pyruvate kinase)
NADH is generated in 6th step:
Glyceraldehyde 3-phosphate forms 1,3 bisphosphoglycerate (using G3P DH)
*Understand table 16.1 in terms of the free-energy changes
a
*What are the enzymes that catalyze the three irreversible steps in glycolysis?
hexokinase, phosphofructokinase, pyruvate kinase
*Be able to describe the three fates of pyruvate. What does the conversion of pyruvate to
lactate or ethanol actually do for the cell?
3 fates:
- pyruvate can be converted into acetyl CoA, with presence of both Oxygen and mitochondria. (3c to 2c)
- Pyruvate can be converted to Lactate (absence of oxygen), oxidizing NADH to NAD+ (3c to 3c)
- Pyruvate can be converted to ethanol through oxidation of NADH to NAD+ (absence of Oxygen, 2c to 2c)
*Understand how galactose and fructose enter into glycolysis.
Fructose from table sugar or high fructose and galactose (milk sugar) are converted into glycolytic intermediates.
They are both metabolized in the liver.
Galactose reacts with ATP to from glucose-1 phosphate (which can then be converted to glucose 6-phosphate by phosphoglucomutase.
In liver, fructose is metabolized by fructose 1-phosphate pathway.
other tissues, such as adipose tissue, fructose is directly phosphorylated to hexokinase.
*How is glycolysis regulated in skeletal muscle? Why is glycolysis regulated differently in
the liver? How is it regulated in the liver?
a
*What is aerobic glycolysis?
a
*Become familiar with the family of glucose transporters (Table 16.3)
GLUT1-5 facilitate the movement of glucose.
GLUT 1- all mammalian tissues; basal glucose uptake in BRAIN-BARRIER
GLUT 2- acts as glucose sensor. in PANCREAS beta cells, regulates insulin; in LIVER remove excess glucose from blood (insulin dependent)
GLUT 3- in all mammalian tissues, basal glucose uptake in NEURONS, WBC.
GLUT 4- MUSCLE and FAT cells, insulin sensitive/dependent. The am amount in muscle PM increases with endurance training
GLUT 5 - in small intestine, transporter for fructose
Why is glucose such a prominent fuel in all life forms?
- Glucose may have been available for primitive biochemical systems, because it can form under prebiotic conditions
- Glucose is the most stable hexose
- Glucose has a low tendency to non-enzymatically glycosylate proteins.
What is the rate limiting step in glycolysis?
converting fructose-6-phosphate into fructose 1, 6 bisphosphate using PHOSPHOFRUCTOKINASE (PFK). irreversible step
What are the three enzymes that catalyze irreversible reactions in metabolic pathways, and serve as potential control sites?
The three enzymes that have irreversible reactions:
- Hexokinase
- phosphofructokinase
- pyruvate kinase
What facilitates them movement of glucose across the cell membrane?
A family of 5 glucose transporters called GLUT1-5 facilitate the movement of glucose.
What kind of isoforms do pyruvate kinase have?
What happens to pyruvate kinase, with low blood glucose?
L form- Liver
M form- Muscle
allosteric regulation is similar for both forms except alanine (only L form affected)
Only L form controlled by phosphorylation/dephosphorylation.
Low blood glucose:
-Glucagon triggers cAMP cascade that leads to phosphorylation of pyruvate kinase (LOWERS ACTIVITY) minimizes liver from consuming glucose, when it is needed by brain and muscle.
Which compounds are key regulators of phosphofructokinase in the liver?
CITRATE (reports on status of citric acid cycle) and FRUCTOSE-2, 6 BISPHOSPHATE.
Citrate INHIBITS phosphofructokinase, while 2,6, bisphosphate is POWERFUL ACTIVATOR (overriding other molecules)
What is the cause of lactose intolerance, or HYPOLACTASIA?
Lactose intolerance, occurs because most adults lack the enzyme to degrade lactose. (they do not have lactase that will convert lactose to glucose and galactose).
What are pathological conditions caused by excess fructose consumption?
What enzyme gets bypassed in the liver and why?
Excess fructose consumption linked to obesity, fatty liver, and development of type 2 diabetes.
Due to manner in which fructose is processed in liver, PFK (key regulatory enzyme of glycolysis) is bypassed in liver
-excess acetyl COA is then synthesized and converted to fats.
What must be present for Glycolysis and ATP synthesis to continue? How is NAD+ regenerated?
Conversion of glucose into pyruvate generates ATP, but for ATP synthesis to occur, NADH must be REOXIDIZED to NAD+.
NAD+, coenzyme is derived from vitamin B3 (NIACIN).
NAD+ can be regenerated by further oxidation of pyruvate to CO2, or by formation of ethanol and lactate from pyruvate.
What is the net reaction for glycolysis?
1 glucose molecule + 2 ADP and 2 Pi + 2 NAD+ will form 2 pyruvate + 2 ATP +2 NADH + 2H and 2 H20.
How is PEP (Phosphoenolpyruvate) formed? What makes this a special compound and why? What happens after this compound made?
- 3-phosphoglycerate is converted into 2-phosphoglycerate by phosphoglycerate mutase.
- Then a dehydration reaction catalyzed by ENOLASE, results in production of phosphoenol pyruvate (PEP).
PEP is special because it is HIGH phosphoryl-transfer compound due to the presence of phosphate trapping the compound in unstable enol tautomer.
ADP is then phosphorylated at expense of PEP, generating ATP and pyruvate, catalyzed by pyruvate kinase.
What compounds and enzyme are used to form fructose 6-phosphate in glycolysis?
Glucose 6-phosphate will convert to fructose 6-phosphate using PHOSPHOGLUCOSE ISOMERASE ENZYME.
reaction is readily reversible.
