UNIT2_CHO Metabolism NTK Flashcards
In addition to generating ATP, the citric acid cycle generates important molecules for other metabolic pathways:
succinyl CoA is used in _______ synthesis.
heme
In addition to generating ATP, the citric acid cycle generates important molecules for other metabolic pathways:
oxaloacetate is used in process/pathway?
gluconeogenesis
In addition to generating ATP, the citric acid cycle generates important molecules for other metabolic pathways:
oxaloacetate and α-ketoglutarate are used in __________ synthesis
amino acid
In addition to generating ATP, the citric acid cycle generates important molecules for other metabolic pathways:
citrate is involved in the pathway of ________ synthesis
fatty acid
What is the order of the citric acid cycle?
“Citrate Is Krebs’ Starting Substrate For Making Oxaloacetate.”
Citrate Isocitrate α-Ketoglutarate Succinyl CoA Succinate Fumarate Malate Oxaloacetate
For each turn, the citric acid cycle produces how many GTP, ATP, NADH, FADH2, CO2?
For each turn, the citric acid cycle produces:
0 ATP 1 GTP 3 NADH 1 FADH2 2 CO2
For each turn, the citric acid cyclea total of ____ ATP molecules are made per acetyl CoA., due to the electron transport chain.
10-12 ATP
The α-ketoglutarate dehydrogenase complex is one of the three regulated steps of the citric acid cycle. It requires many cofactors, including:
Vitamin B1 (Thiamine) Vitamin B2 (Riboflavin) Vitamin B3 (Niacin) Vitamin B5 (Pantothenic Acid) Lipoic acid
α-ketoglutarate dehydrogenase is inhibited by: (4)
NADH
Succinyl CoA
ATP
GTP
What enzyme converts α-ketoglutarate to succinyl-CoA?
The α-ketoglutarate dehydrogenase complex
During what steps of the TCA cycle are CO2 released?
Isocitrate to α-ketoglutarate
&
α-ketoglutarate to Succinyl-CoA
What enzyme oxidizes malate to oxaloacetate, and the cycle can begin anew?
Malate dehydrogenase
Mitochondrial _________nconverts fumarate to malate
fumarase
FADH2 is produced in the conversion of succinate to fumarate. This reaction is catalyzed by what enzyme?
succinate dehydrogenase
What enzyme is embedded in the inner mitochondrial membrane as complex II of the electron transport?
succinate dehydrogenase
aka Complex II
The __________ enzyme complex catalyzes oxidation of succinate to fumarate.
succinate dehydrogenase
______________ converts succinyl-CoA to succinate and CoA. In the process, substrate-level phosphorylation produces GTP.
Succinyl-CoA synthetase
Succinyl-CoA synthetase converts succinyl-CoA to _________ & _________. In the process, substrate-level phosphorylation produces GTP.
succinate and CoA
What enzyme catalyses that reaction where the 2nd CO2 is released?
α-ketoglutarate dehydrogenase
What enzyme catalyses that reaction where the 1st CO2 is released?
isocitrate dehydrogenase
The α-ketoglutarate dehydrogenase complex converts __________ to succinyl-CoA.
α-ketoglutarate
The ___________ enzyme complex converts α-ketoglutarate to succinyl-CoA.
α-ketoglutarate dehydrogenase
What reaction in the TCA cycle produces GTP?
Succinyl-CoA synthetase converts succinyl-CoA to succinate and CoA.
In the process, substrate-level phosphorylation produces GTP. The entire reaction is:
Succinyl CoA + Pi + GDP ↔ Succinate + CoA + GTP
What reaction in the TCA cycle produces FADH2?
Succinate to Fumarate via
Succinate dehydrogenase. (Complex II on the inner mitochondria membrane in the ETC)
What enzyme concerts PEP to pyruvate?
Pyruvate Kinase
What is formed after GA3P?
1,3-biphosphoglycerate (1,3BPG)
What is the enzyme that sequesters glucose within the cells of skeletal muscles?
Hexokinase
Glucokinase is a high-capacity isoenzyme of hexokinase expressed what organs?
It is induced by insulin and is a key component of insulin’s hypoglycemic effect.
in the liver and pancreas
What is the RDS of Glycolysis?
F6P is phosphorylated to fructose-1,6-bisphosphate (F1,6BP) by phosphofructokinase-1 (PFK-1)
In what cellular compartment does glycolysis occur?
Cytosol
What are the key enzymes that regulate Glycolysis?
- Hexokinase
- Glucokinase
- Phosphofructokinase-1 (PFK-1)
- Pyruvate Kinase
Is Hexokinase or Glucokinase inhibited by G-6-P? Why is this important?
Hexokinase is inhibited by G-6-P.
The regulation of Hexokinase by G6P prevetns the over consumption of ATP during the rxn.
What is the Km and V_max of Hexokinase?
What is the Km and V_max of Glucokinase?
What does this mean?
Hexokinase: Low Km=High Affinity & low capacity=low V_max
Glucokinase: High Km=Low affinity & high capacity=high V_max.
Also peripheral tissue to get glucose even in a fasted state.
Is Hexokinase or Glucokinase STIMULATED by insulin? Why is this important?
Glucokinase is stimulated by insulin!
What is MODY and what enzyme is defective?
Glucokinase genetic mutationson chromosome 7 may result in maturity-onset diabetes of the young (MODY).
Glucokinase, within the beta-cells of the pancreas, acts as a glucose sensor, thus when a mutation is present, impaired glucose sensation occurs leading to persistant hyperglycemia and impaired insulin secretion.
Glucokinase is further regulated by fructose-6-phosphate. Explain how?
F6P binds to the same receptor as glucokinase regulatory protein (GKRP), thereby enhancing GKRP’s ability to inhibit glucokinase.
Phosphofructokinase-1 activity is increased in the presence of what molecule? What type of regulation is this?
AMP
&
fructose-2,6-bisphosphate (F2,6BP)
which act as allosteric activators.
Phosphofructokinase-1 activity is decreased in the presence of what molecule?
Citrate and ATP (high energy state)
Phosphofructokinase-2 (PFK2) / fructose-2,6-bisphosphatase (F26BPase) is a bifunctional enzyme regulating phosphofructokinase-1. PFK2 is favored under the following pathway: (6)
- High blood glucose causes insulin secretion
- Insulin activates protein phosphatase
- Protein phosphatase dephosphorylates PFK2
- PFK2 then predominates over F26BPase
- PFK2 synthesizes fructose-2,6-bisphosphate from fructose-6-phosphate
- F26BP is a potent activator of PFK-1
Phosphofructokinase-2 / fructose-2,6-bisphosphatase is a bifunctional enzyme regulating phosphofructokinase-1. F26BPase is favored under the following pathway: (5)
- Low blood glucose elevates glucagon secretion
- Glucagon secretion causes phosphorylation of PFK-2 via cAMP pathway
- F2,6BPase activity now predominate
- F26BPase synthesizes fructose-6-phosphate from fructose-2,6-bisphosphate
- Lower concentrations of F26BP decreases the activity of PFK-1
What increases Pyruvate Kinase activity?
presence of F1,6BP and PEP
How is Pyruvate Kinase inhibited?
Allosterically, by ATP & Alanine
Pyruvate kinase may also be inhibited by low blood glucose levels, allowing for PEP to enter gluconeogenesis via the following pathway: (4)
- Low Glucose levels detected.
- INcreased glucagon secretion.
- Increased cAMP and PKA activity
- Phosphorylation leads to inactivation of pyruvate kinase
What molecule results from the carboxylation reaction of pyruvate?
Oxaloacetate
via Pyruvate carboxylase
The majority of pyruvate is metabolized to lactate by lactate dehydrogenase in the following tissues:(6)
- Cornea
- Lens
- Red blood cells
- White blood cells
- Kidney medulla
- Testes
What enzyme converts pyruvate to alanine and what is the cofactor that is needed?
alanine aminotransferase (ALT)
Transamination rxn.
Cofactor is Pyridoxal phosphate (vitamin B6 .
Pyruvate can be converted to the following molecules and enter their associated pathways: (4 rxns)
1) acetyl-CoA → citric acid cycle
2) oxaloacetate → TCA cycle or gluconeogenesis
3) alanine → glucose-alanine cycle
4) lactate → Cori cycle (hepatic gluconeogenesis from lactate)
How can pyruvate enter the Cori Cycle?
Pyruvate –> Lactate
via lactate dehydrogenase (LDH)
Can pyruvate be made to enter the Pentose Phoshate pathway?
NO!
Pyruvate can only enter the following pathways:
1) acetyl-CoA → citric acid cycle
2) oxaloacetate → TCA cycle or gluconeogenesis
3) alanine → glucose-alanine cycle
4) lactate → Cori cycle (hepatic gluconeogenesis from lactate)
Overall, how many ATP are consumed for each round of the Cori cycle? What is the result?
4 net ATP.
therefore, there is a metabolic shift to the liver.
Glycolysis and anaerobic metabolism in the muscle cells generate 2 ATP per glucose; gluconeogenesis in the liver consumes ___ ATP to generate one glucose from two lactate.
6 ATP
Glucose-6-phosphatase catalyzes this reaction, which occurs in the _______________ of the cell. The sequestration of this enzyme assures it does not compete with glucokinase/hexokinase during glycolysis.
smooth endoplasmic reticulum
What inhibit fructose-1,6-bisphosphatase? (2)
Fructose-2,6-bisphosphate and AMP
As the rate-limiting step of gluconeogenesis, fructose-1,6-bisphosphatase has many allosteric activators and inhibitors. What are the activators?
Citrate, ATP, and acetyl-CoA allosterically activate fructose-1,6-bisphosphatase, as they are indicative of a heavily glycolytic environment.
What is the RDS reaction in Gluconeogenesis?
The conversion of fructose-1,6-bisphosphate to fructose-6-phosphate.
catalyzed by fructose-1,6-bisphosphatase.
___________ is transported to the cytosol using the malate shuttle.
Oxaloacetate
The 2nd reaction of gluconeogenesis: Oxaloacetate → Phosphoenolpyruvate (PEP).
What enzyme catalyzes this reaction?
PEP carboxykinase catalyzes this reaction, which occurs in the cytosol.
excess __________ is indicative of a need for a shift from glycolysis to gluconeogenesis.
acetyl-CoA
__________ is a cofactor of the pyruvate → oxaloacetate reaction catalyzed by pyruvate carboxylase.
Biotin
The 1st reaction of gluconeogenesis: Pyruvate → Oxaloacetate.
What enzyme catalyzes this reaction?
Pyruvate carboxylase catalyzes this reaction, which occurs in the mitochondria.
What metabolites has an entry point that is the furthest upstream among the non-pyruvate substrates?
All triacylglycerides (TAGs) can be metabolized to form glycerol, which can enter gluconeogenesis through several reactions resulting in the formation of DHAP.
What non-pyruvate substrae enters gluconeogenesis thru multi-step conversion to OAA?
Metabolites of fatty Acid Metabolism enter Gluconeogenesis as PROPIONYL-CoA
ODD-number fatty acids only! even-chain fatty acids do not produce propionyl-CoA.
What two carbon substrates can enter gluconeogenesis thru DIRECT conversion to PYRUVATE?
Alanine & Lactate
What step in gluconeogenesis is 2 GTP per glucose consumed?
OAA –> PEP
via PEP caroxykinease
Where is the cell does Pyruvate Carboxylase work?
Mitochondria:
Pyruvate –> OAA
Where is the cell does G6P dephosphorylation occur?
Smooth ER
Muscle cells cannot raise blood glucose via gluconeogenesis because they lack ____________. Because phosphorylated glucose is unable to exit the cell, glucose remains trapped in the myocytes.
glucose-6-phosphatase
What substrates inhibit fructose-1,6-bisphosphatase? (2)
Fructose-2,6-bisphosphate
&
AMP
What stimulates Pyruvate Carboxylase to convert pyruvate to OAA?
acetyl-CoA
In gluconeogenesis:
Fructose-1,6-bisphosphate → Fructose-6-phosphate
is catalyzed by what enzyme?
Fructose-1,6-bisphosphatase;
occurs in the cytosol.
In glycogen, the linear bonds are ___________ linkages whereas the branching bonds are __________ linkages.
Linear bonds: α-(1,4) glycosidic
Branching bonds: α-(1,6) glycosidic
Glycogen is synthesized and stored primarily where?
in the cytoplasm of hepatocytes and skeletal muscle cells.
__________ is a highly branched (branching every ~10 glucosyl residues) glucose polymer used as the main storage form of glucose in the body.
Glycogen
The first step in glycogenesis is:
Glucose + 1 ATP → Glucose-6-Phosphate + ADP
This reaction requires what cofactor?
magnesium
What is the second step of glycogensis?
What is the enzyme involved?
glucose-6-phosphate is isomerized (“mutated”) to glucose-1-phosphate in a reversible reaction.
phosphoglucomutase
What is phosphoglucomutase?
The enzyme that isomerizes (“mutates”) glucose-6-phosphate to glucose-1-phosphate.
What is he third step of glycogenesis?
What is the enzyme involved?
glucose-1-phosphate + UTP → UDP-glucose + 2Pi
glucose-1-phosphate uridylyltransferase (aka UDP-glucose pyrophosphorylase)
What is the RDS rxn in glycogen synthesis?
the addition of UDP-glucose to a pre-existing glycogen chain via a α(1,4)-glycosidic linkage.
The enzyme that catalyzes the addition of UDP-glucose to an existing glycogen molecule is ____________.
glycogen synthase
glycogen synthase is activated by:
glycogen synthase is inhibited by:
glycogen synthase is activated by: insulin and glucose.
glycogen synthase is inhibited by: Glucagon and epinephrine
Branching enzyme makes branch points in a linear glycogen molecule using α-(1,6) glycosidic bonds, about every ____________.. What does this allow for?
10 glucosyl residues.
allows for more compact storage of a greater number of glucose molecules.
What is the enzyme that catalyzes the rate-determining step of glycogenolysis?
glycogen phosphorylase.
What enzyme removes the phosphate from glucose-6-phosphate to create free glucose?
Glucose 6-phosphatase
What is the possible fates of glucose-6-phosphate? (3)
- Glycolysis
- Pentose phospahte pathway (aka hexose monophosphate shunt)
- converted to free glucose in the liver.
What provides the energy for creating the proton gradient in the electron transport chain?
the flow from (e-), provided from NADH and FADH2, thru the ETC provide the energy to pump protons into the INNER MITOCHONDRIAL inter-membrane space to create the E-C proton gradiant
What is thermogenin w.r.t. the ETC?
Thermogenin in brown fat is an uncoupling agent that disrupts the proton gradient. This is physiologically used to generate heat in infants, who possess brown fat.
What are the two shuttles used to transport NADH across the inner mitochondrial membrane?
Which one is more energy efficient?
- Malate-aspartate shuttle; more efficient!
2. G3P shuttle
Complex II is also what same enzyme of the citric acid cycle?
succinate dehydrogenase
What is Complex V of the ETC also known as? What powers this complex?
ATP Synthase (Complex V): uses the electrochemical proton gradient created by the ETC to produce ATP from ADP and Pi.
As a toxin, what enzyme in the ETC does Carbon Monoxide bind to?
Cytochrome C Oxidase.
CN (Cyanide) also binds to this enzyme.
both consume O2 and deprives the mitochondria of its final (e-) acceptor.
Which toxin of the ETC binds to and inhibits ATP synthase?
Oligomycin
Which toxin transports protons across the mitochondrial membrane, inhibiting the electron transport system?
2,4-DiNitroPhenol
2,4-Dinitrophenol and increased doses of aspirin increase the permeability of the inner mitochondrial membrane leading to a _____1_____ proton gradient and _____2_____ oxygen consumption. Heat is generated instead of ATP (this explains the fever generated following toxic doses of aspirin.)
- decreased proton gradient
2. increased O2 consumption
What are the mobile (e-) carriers of the ETC?
Coenzyme Q & Cytochrome C
