Chapter 9: Carbohydrate Metabolism: Glycolysis, Glycogen, Gluconeogenesis, and the Pentose Phosphate Pathway Flashcards
How many glucose transporters are there?
4 - GLUT 1 through 4
GLUT ____ is a low-affinity transporter in hepatocytes and pancreatic cells.
2
After a meal, blood traveling through the ____________ ________ vein from the intestine is rich in glucose. GLUT ____ captures the excess glucose primarily for storage.
hepatic portal; 2
What is Km?
The concentration of substrate when an enzyme is active at half of its maximum velocity
The lower the Km, the higher is what?
the enzyme’s affinity for the substrate
When the glucose concentration drops below the Km for the transporter, much of the remainder of glucose does what?
Bypasses the liver and enters the peripheral circulation
The Km is quite high - what does this mean?
The liver will pick up glucose in proportion to its concentration in the blood.
i.e. The liver will pick up excess glucose and store it preferentially after a meal, when blood glucose is high
In the beta-islet cells of the pancreas, GLUT ____, along with the glycolytic enzyme ____________, serves as the glucose sensor for insulin release.
2; glucokinase
GLUT ____ is in adipose tissue and muscle and responds to the glucose concentration in peripheral blood.
4
The rate of glucose transport in adipose and muscle is increased by ________, which stimulates the movement of additional GLUT ____ transporters to the membrane by a mechanism involving exocytosis.
insulin; 4
The Km of GLUT4 is close to the normal glucose levels in blood. This means that the transporter is saturated when?
When the blood glucose levels are just a bit higher than normal
How do cells with GLUT4 transporters increase their intake of glucose?
Increase the number of GLUT 4 transporters on their surface
Although basal levels of transport occur in all cells independently of insulin, the ________ rate increases in ________ tissue and ________ when insulin levels rise.
transport; adipose, muscle
Muscle stores excess glucose as ____________, and adipose tissue requires glucose to form dihydroxyacetone phosphate (DHAP), which is converted to ____________ ____________ to store incoming fatty acid as ________________.
glycogen, glycerol phosphate, triacylglycerols
All cells can carry out glycolysis. In a few tissues, specifically ____ ________ ________, glycolysis represents the only energy yielding pathway available because they lack mitochondria, which are required for TCA, ETC, oxidative phosphorylation, and fatty acid metabolism (beta-oxidation).
red blood cells
________ is the major monosaccharide that enters the glycolysis pathway, but others like ____________ and ____________ can also feed into it.
glucose; galactose and fructose
Glycolysis is a cytoplasmic pathway that converts ____________ into 2 ____________ molecules. This releases ____________ captured in 2 substrate-level ________________ and 1 ____________ reaction.
glucose; pyruvate
phosphorylations; oxidation
If a cell has mitochondria and oxygen, the energy carriers produced in glycolysis, ________, can feed into the ________ ____________ pathway to generate energy for the cell.
NADH; aerobic respiration
If either mitochondria or oxygen is lacking, like in RBCs or exercising skeletal muscle, then glycolysis can happen ________________, although some available energy is lost.
anaerobically
Glycolysis also provides ________________ for other pathways, e.g. in the liver, glycolysis is part of the process in which excess ________ is converted to fatty acids for storage.
intermediates; glucose
Glucose enters the cell by ____________ diffusion or ________ transport. The enzyme ____________ (or ____________ in the liver) convert glucose to ____________ ____-____________.
facilitated, active; hexokinase, glucokinase; glucose 6-phosphate
Hexokinase is found where? What inhibits it?
Widely distributed in tissues and inhibited by glucose 6-phosphate
Glucokinase is only found in ________ cells and ____________ (beta-islet) cells. It is induced by ________________.
liver, pancreatic; insulin
Hexokinase has a ____ Km, meaning it reaches max velocity at a ____ [glucose].
low; low
Glucokinase has a ____ Km, meaning it acts on glucose proportionally to its concentration.
high
________________-____ is the rate limiting enzyme and main control point in glycolysis.
phosphofructokinase-1
Phosphofructokinase-1 phosphorylates ____________ ____-____________ to ____________ ____-____________ using ________.
fructose 6-phosphate to fructose-1,6 bisphosphate using ATP
PFK-1 is inhibited by ____ and ________, and activated by ____.
ATP and citrate; AMP
Why is PFK-1 inhibited by ATP and citrate?
ATP - because glycolysis is off when the cell has sufficient energy (high ATP)
Citrate - high levels imply cell is producing enough energy
________ stimualtes and ____________ inhibits PFK-1 in hepatocytes.
Insulin; glucagon
Insuling activates ________________-____, which converts ____________ ____-________ to ____________ ____-____________.
phosphofructosekinase-2; fructose 6-phosphate to fructose 2,6-bisphosphate
What activates PFK-1?
F26BP
____________ inhibits PFK-2, which lowers ____________, which ultimately inhibits PFK-1.
F26BP; glucagon
________ is found mostly in the liver. By activating PFK-1, it allows cells to do what?
PFK-2; allows cells to keep doing glycolysis even if the cell is satisfied, that way the metabolites can be used for production of glycogen, fatty acids, and other storage molecules, rather than just be used for ATP production
What enzyme catalyzes the oxidation and addition of Pi to glyceraldehyde 3-phosphate?
glyceraldehyde-3-phosphate dehydrogenase
Once glyceraldehyde 3-phosphate is phosphorylated, it produces what high-energy intermediate? What is also reduced?
1,3-bisphosphoglycerate; NAD+ to NADH
If glycolysis is aerobic, the NADH reduced by glyceraldehyde-3-P dehydrogenase can be used for what?
Oxidized by the mitochondrial ETC to provide energy for ATP synthesis by oxidative phosphorylation
____-____________ ________ transfers the high-energy phosphate from ____-____________ to ADP, which forms what two things?
3-phosphoglycerate kinase; 1,3-bisophosphoglycerate; ATP and 3-phosphoglycerate
Pyruvate kinase phosphorylates ADP using ________________. It is activated by what enzyme?
phosphoenolpyruvate; F16BP
Without oxygen, ____________ will occur. The key enzyme here is ____________ ________________.
fermentation; lactate dehydrogenase
Lactate dehydrogenase oxidizes ________ to ________, replenishing the oxidized coenzyme for ________________-____-____ ________________.
NADH to NAD+, glyceraldehyde-3-phosphate dehydrogenase
Without mitochondria and oxygen, glycolysis would stop when all the available ________ has been reduced to ________. By reducing pyruvate to ________ and oxidizing NADH to NAD+, lactate dehydrogenase prevents this problem.
NAD+, NADH; lactate
________________ ________ (DHAP) is used in hepatic and adipose tissue for ____________ synthesis. It is formed from what?
dihydroxyacetone phosphate; fructose 1,6-bisphosphate
DHAP can be isomerized to ________ ____-________, which can then be converted to ____________, the backbone of triacylglycerols.
glycerol 3-phosphate; glycerol
Which two intermediates are used to generate ATP by substrate-level phosphorylation? These are the only ATP gained in anaerobic respiration.
- 1,3-bisphosphoglycerate
- phosphoenolpyruvate
Which 3 enzymes catalyze reactions that are irreversible in glycolysis?
- glucokinase or hexokinase
- PFK-1
- pyruvate kinase
In RBCs, ____________ glycolysis is the only pathway for ATP production, yielding a net ____ ATP per glucose.
anaerobic; 2
RBCs have ________________ ________, which produces ____-________ from ____-________ in glycolysis.
bisphosphoglycerate mutase; 2,3-BPG from 1,3-BPG
What do mutases do?
Move a functional group from one place in a molecule to another (in this case phosphate)
____-________ binds allosterically to the beta-chains of hemoglobin A and ____________ its affinity for oxygen.
2,3-BPG, decreases
An important source of galactose is ____________.
lactose
Lactose is hydrolyzed to galactose and glucose by ____________.
lactase
Once transported into tissues, galactose is phosphorylated by ________________.
galactokinase
Galactose 1-phosphate is converted to ____________ ____-________ by ____________ and what enzyme?
glucose 1-phosphate; epimerase, galactose-1-phosphate uridyltransferase
Epimerases are enzymes that catalyze the conversion of what to what?
One sugar epimer to another
Epimers are ____________ that differ where?
Diastereomers, differ at exactly 1 chiral carbon
Galactokinase does what?
Phosphorylates galactose to galactose 1-phosphate (ATP to ADP)
________ is found as part of the disaccharide sucrose.
Fructose
The liver phosphorylates fructose using ____________ to trap it in the cell.
fructokinase
Once fructose is phosphorylated into fructose 1-phosphate, it is cleaved into ________________ and ________ by what enzyme?
glyceraldehyde, DHAP; aldolase B
Pyruvate from ____________ glycolysis enters mitochondria, where it may be converted to ________-________ for entry into the cirtic acid cycle IF ATP is needed, or for ________ ________ synthesis if sufficient ATP is present.
aerobic; acetyl-CoA; fatty acid
The ____________ ________________ ________ reaction is irreversible and cannot be used to convert acetyl-CoA to pyruvate or to glucose.
pyruvate dehydrogenase complex
Pyruvate dehydrogenase in the liver is activated by ____________, whereas in the nervous system, the enzyme is not responsive to hormones. This makes sense because high insulin levels signal to the liver that the individual is what?
insulin; well-fed
When well-fed, the liver should not only burn glucose for energy, but shift the fatty acid equilibrium toward what instead of what?
production/storage instead of oxidation
What are the 3 possible fates of pyruvate?
- conversion to acetyl-CoA by pyruvate dehydrogenase
- conversion to lactate by lactate dehydrogenase
- conversion to oxaloacetate by pyruvate carboxylase
Pyruvate dehydrogenase is inhibited by what?
Its product, acetyl-CoA
Glycogen stored in the liver is mobilized when? How about muscle glycoen?
Between meals to prevent low blood sugar; for muscle contraction
Plants also store excess glucose in long alpha-linked chains of glucose called ____________.
starch
____________ is the synthesis of glycogen granules. It begins with a core protein called ____________.
glycogenesis; glycogenin
Glucose addition in glycogenesis begins with ____________ ____-____________, which is converted to ____________ ____-________.
glucose 6-phosphate to glucose 1-phosphate
Glucose 1-phosphate is activated by coupling to a molecule of ____________ ________________, which permits its integration into the glycogen chain by ________________ ____________.
uridine diphosphate; glycogen synthase
Glucose 1-phosphate’s activation occurs when it interacts with ____________ ____________ to form UDP-glucose and a ________________.
uridine triphosphate; pyrophosphate
____________ ____________ is the rate-limiting enzyme of glycogen synthesis.
Glycogen synthase
What inhibits glycogen synthase?
Epinephrine and glucagon
____________ ____________ is responsible for introducing alpha-1,6-linked branches into the glycogen granule as it grows.
branching enzyme
________________ is the process of breaking down glycogen using what enzyme?
Glycogenolysis; glycogen phosphorylase
In contrast to a hydrolase, a phosphorylase breaks bonds using what instead of what?
inorganic phosphate, water
Glycogen phosphorylase breaks what type of bonds and releases what?
alpha-1,4 glycosidic bonds, releases glucose 1-phosphate
Glycogen phosphorylase is activated by ____________ in the liver, so that glucose can be provided for the rest of the body. In skeletal muscle ,it is activated by ________ and ____________, which signal that the muscle is active and requires more glucose. It is inhibited by ________.
glucagon; AMP and epinephrine; ATP
Debranching enzyme is a 2-enzyme complex that deconstructs the branches in glycogen that have been exposed by what enzyme?
glycogen phosphorylase
The liver maintains glucose levels in blood during fasting through either ____________ or ________________.
glycogenolysis or gluconeogenesis
What promotes glycogenolysis and gluconeogenesis?
- Glucagon
- Epinephrine
What inhibits gluconeogenesis and glycogenolysis?
Insulin
Glucogenic amino acids (except leucine and lysine) can be converted into intermediates that feed into ________________, while ketogenic amino acids can be converted into ____________ ____________, an alternative fuel.
gluconeogenesis; ketone bodies
Pyruvate carboxylase is a mitochondrial enzyme activated by ____________-________. The product, ________________, is a citric acid cycle intermediate that cannot leave the mitochondrion. Instead, it is reduced to ____________, which can then leave.
acetyl-CoA; oxaloacetate, malate
Once in the cytoplasm, malate can be oxidized to ________________.
oxaloacetate
____________________ ________________ is induced by glucagon and cortisol, which generally act to raise blood sugar levels. It converts OAA to PEP in a reaction that requires ________.
phosphoenolpyruvate carboxykinase; GTP
________________________ in the cytoplasm is a key control point of gluconeogenesis and represents the rate-limiting step of the process. It reverses the action of PFK-1 (the rate limiting step of ____________) by removing phosphate from F16BP to produce F6P.
fructose-1,6-bisphosphatase; glycolysis
F16BP is activated by ____ and inhibited by ____ and ________.
ATP; AMP, F26BP
____________________ is found only in the lumen of the ER in liver cells.
glucose 60phosphatase
What are the 2 major functions of the pentose phosphate pathway?
- produce NADPH
- produce ribose 5-phosphate for nucleotide synthesis
PPP begins with ____________ ____-____________, ends with ____________ ____-____________, and is irreversible
glucose 6-phosphate, ribulose 5-phosphate
The production of ribulose 5-phosphate produces ________ and involves an important rate-limiting enzyme, what is it?
NADPH; glucose-6-P dehydrogenase
In the cell, ________ acts as a high-energy electron acceptor. It is a potent oxidizing agent (and reduces itself in the process).
NAD+
________ produced from the reduction of NAD+ can then feed into the ETC to indirectly produce ________.
NADH, ATP
Conversely, ____________ primarily acts as an electron donor in a number of biochemical reactions. It is a potent reducing agent (and is oxidized itself during the process).
NADPH
