Biochemistry Unit 3 Exam

82 flashcards · Other · by John Mark Webb

Phosphofructokinase-1 Function(s)? Inhibitor(s)? Activator(s)? Reversible?
fructose 6-phosphate phosphorylated to fructose 1,6-bisphosphate using ATP rate-limiting step main control point of glycolysis inhibited by ATP (allosteric) inhibited by citrate (allosteric) activated by AMP activated by *fructose 2,6-bisphosphate* irreversible
Glyceraldehyde-3-Phosphate Dehydrogenase Function(s)? Inhibitor(s)? Activator(s)? Reversible?
catalyzes an oxidation and addition of inorganic phosphate to its substrate, glyceraldehyde 3-phosphate which produces 1,3-bisphosphoglycerate and the reduction of NAD+ to NADH first energy conserving reaction cannot run reaction without NAD+ inhibited by low NAD+ reversible
Phosphoglycerate Kinase Function(s)? Inhibitor(s)? Activator(s)? Reversible?
transfers the high-energy phosphate from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate substrate-level phosphorylation not dependent on oxygen reversible
Pyruvate Kinase Function(s)? Inhibitor(s)? Activator(s)? Reversible?
catalyzes a substrate-level phosphorylation of ADP using the high-energy substrate phosphoenolpyruvate (PEP) activated by fructose 1,6-bisphosphate from PFK-1 reaction feed-forward activation irreversible
What happens in the absence of oxygen?
fermentation
What is the key fermentation enzyme?
lactate dehydrogenase oxidizes NADH to NAD+ replenishes the oxidized coenzyme for glyceraldehyde-3-phosphate dehydrogenase
How does lactate dehydrogenase prevent glycolysis from stopping when all the available NAD+ has been reduced to NADH?
reducing pyruvate to lactate and oxidizing NADH to NAD+
When oxygenation is poor, how is most cellular ATP generated?
anaerobic glycolysis
Lactate production (increases / decreases) when oxygenation is poor and during anaerobic glycolysis.
increases
What are the 4 irreversible enzymes of glycolysis?
hexokinase glucokinase (hexokinase IV; only in liver) PFK-1 pyruvate kinase
What two enzymes are required for the fermentation of glucose to ethanol?
pyruvate decarboxylase alcohol dehydrogenase
Pyruvate Dehydrogenase Complex name of 3 enzymes
E1 - pyruvate dehydrogenase E2 - dihydrolipoyl transacetylase E3 - dihydrolipoyl dehydrogenase overall reaction is the oxidative decarboxylation of pyruvate to acetyl-CoA
What is the difference between NADPH and NADH?
NAD+ acts as a high-energy electron acceptor and is a potent oxidizing agent NADPH primarily acts as an electron donor and is a potent reducing agent
What are the two major functions of the pentose phosphate pathway?
production of NADPH source of ribose 5-phosphate for nucleotide synthesis THIS OCCURS IN THE CYTOPLASM OF ALL CELLS
Glucose 6-phosphate dehydrogenase (part of the PPP) Function(s)? Inhibitor(s)? Activator(s)? Reversible?
converts glucose 6-phosphate to 6-phosphogluconate inhibited by NADPH activated by NADP+ activated by insulin first enzyme of PPP responsible for the production of the first NADPH irreversible
What is the medical importance of NADPH?
it maintains a supply of reduced glutathione to protect against reactive oxygen species (the body's natural antioxidant) it also regulates the entry of glucose 6-phosphate into other pathways
How is the first NADPH synthesized?
glucose 6-phosphate is converted to 6-phosphogluconate and this requires NADP+ to be reduced to NADPH
Regarding the PPP, how are pentose phosphates recycled to glucose 6-phosphate?
Usually in tissues that require NADPH primarily, the nonoxidative phase uses two key enzymes: transketolase and transaldolase
What is the role of biotin in biochemical reactions?
it is a coenzyme; it is a carrier of activated bicarbonate it is a specialized carrier of one-carbon groups in their most oxidized form: CO2 needed for pyruvate carboxylase to turn pyruvate to oxaloacetate
What is the function of the oxidative phase of the pentose phosphate pathway?
produces ribose 5-phosphate and NADPH
What is the function of the nonoxidative phase of the pentose phosphate pathway?
recycles the pentose phosphates to glucose 6-phosphate, allowing continuous production of NADPH with the help of enzymes (transketolase, transaldolase)
Are there any cofactors needed in the pentose phosphate pathway?
YES, TPP is necessary for transketolase in the nonoxidative phase
What are the four primary uses of glucose?
synthesis of complex polysaccharides stored in cells oxidized to 3C compound (pyruvate from glycolysis) to provide ATP oxidized by the PPP to yield ribose 5-phosphate and NADPH (for nucleic acid synthesis and reductive biosynthesis processes, respectively)
Which steps of glycolysis produce ATP?
(7) phosphoglycerate kinase (10) pyruvate kinase
What is meant by the maintenance of a dynamic steady state?
For each metabolic reaction in a pathway, the substrate is provided by the preceding reaction at the same rate at which it is converted to product. Thus, although the rate (v) of metabolite flow, or flux, through this step of the pathway may be high and variable, the concentrations of the substrate, S, remains constant. A >v1> S >v2> P When v1 = v2 you can assume [S] is constant. This is homeostasis at the molecular level.
What is flux?
the rate (v) of metabolite flow
What is the flux control coefficient (C)?
it represents the relative contribution of each enzyme to setting the rate at which metabolites flow through the pathway
What is the elasticity coefficient (ε)?
expresses quantitatively the responsiveness of a single enzyme to changes in the concentration of a metabolite or regulator
What is the response coefficient (R)?
expresses the change in pathway flux when P ([insulin]) changes expresses the effect of an outside controller on flux through a pathway
How are the three coefficients (R, C, ε) related?
The responsiveness (R) of a pathway to an outside factor that affects a certain enzyme is a function of (1) how sensitive the pathway is to changes in the activity of that enzyme (the flux control coefficient, C) and (2) how sensitive that specific enzyme is to changes in the outside controlling factor (the elasticity, ε)
What are transcription factors?
nuclear proteins (proteins in the nucleus) that can be activated so that will bind to specific DNA regions (response elements) near a gene's promoter (transcriptional starting point) and activate or repress the transcription of that gene, leading to increased or decreased synthesis of the encoded protein
How can you tell if reactions are at equilibrium, if given Q and K'eq?
if they are within 1 to 2 orders of magnitude of each other, the reaction is near equilibrium
What is AMP-activated protein kinase (AMPK)?
probably the most important mediator of regulation by AMP responds to an increase in [AMP] by phosphorylating key proteins and thus regulating their activities increases glucose transport, activates glycolysis/fatty acid oxidation suppresses energy-requiring processes: synthesis of fatty acids, cholesterol, and protein
Why are some steps of glycolysis far from equilibrium?
under cellular conditions, the process is exergonic because the reaction is so far from equilibrium so it tends to go in the forward direction it is held far from equilibrium because, under prevailing cellular condition of substrate, product, and effector concentrations, the rate of conversion of fructose 6-phosphate to fructose 1,6-bisphosphate is limited by the activity of PFK-1, which is itself limited by the number of PFK-1 molecules present and by the actions of allosteric effectors, this…
What is the difference between control and regulation?
control is when regulated enzymes control the flux through a pathway regulation is when other regulated enzymes rebalance the level of metabolites in response to the change in flux
What glycolytic intermediate causes hexokinase IV (liver) to be drawn back into the nucleus when concentration is high?
fructose 6-phosphate
Why would hexokinase IV be released into the cytosol of a hepatocyte?
high [glucose]
What does hexokinase IV do in hepatocytes?
releases glucose to blood when blood glucose is low uptake and metabolism of glucose when blood glucose is high
An increase in [F26BP] would stimulate _____ and inhibit _____.
glycolysis; gluconeogenesis
An decrease in [F26BP] would stimulate _____ and inhibit _____.
gluconeogenesis; glycolysis
Why is phosphofructokinase rather than hexokinase the pacemaker of glycolysis?
glucose 6-phosphate is not solely a glycolytic intermediate Glucose 6-phosphate can also be converted into glycogen or it can be oxidized by the pentose phosphate pathway (Section 20.3) to form NADPH
What regulates pyruvate kinase?
low blood-glucose levels the glucagon-triggered cyclic AMP cascade leads to its phosphorylation
Phosphoprotein phosphatase
activated by the hormone insulin (indicates that there is a high concentration of glucose in the blood) The enzyme then acts to dephosphorylate other enzymes, such as phosphorylase kinase, glycogen phosphorylase, and glycogen synthase.
What allosterically inhibits pyruvate kinase?
ATP
What are the two fates of pyruvate?
converted to glucose and glycogen via gluconeogenesis oxidized to acetyl-CoA for energy production
What is a positive allosteric modulator of pyruvate carboxylase and a negative modulator of pyruvate dehydrogenase complex, through stimulation of a protein kinase that inactivates the dehydrogenase?
Acetyl-CoA
ChREBP (carbohydrate response element binding protein) Location(s)? Function(s)? Phosphorylated? Turns on what important protein?
liver, adipose tissue, kidney coordinates synthesis of enzymes needed for carb/fat synthesis inactive when phosphorylated (twice) dephosphorylated once to enter nucleus, again to join with partner protein, Mlx, to turn on pyruvate kinase
SREBP-1c, a member of the family of sterol regulatory element binding proteins
turns on synthesis of pyruvate kinase stimulated by insulin depressed by glucagon suppresses gluconeogenic enzymes: glucose 6-phosphatase PEP carboxykinase FBPase-1 DOES NOT SUPPRESS PYRUVATE CARBOXYLASE
CREB (cyclic AMP response element binding protein)
turns on the synthesis of... glucose 6-phosphatase PEP carboxykinase ...in response to the increase in [cAMP] triggered by glucagon
FOXO1 (forkhead box other)
stimulates synthesis of gluconeogenic enzymes suppresses synthesis of glycolysis, PPP, triacylglycerol synthesis
What is Xylulose 5-phosphate and what does it do?
an intermediate of the pentose phosphate pathway, activates phosphoprotein phosphatase PP2A, which dephosphorylates several target proteins, including PFK-2/FBPase-2, tilting the balance toward glucose uptake, glycogen synthesis, and lipid synthesis in the liver.
What five coenzymes are required by the pyruvate dehydrogenase complex?
CoA-SH NAD+ TPP lipoate FAD
What is a synthase?
catalyzes synthesis of a biological compound without the use of ATP
What is a synthetase?
synthesizes biological compounds using ATP
What is a ligase?
catalyzes the joining of two large molecules by forming a new chemical bond, usually with hydrolysis
What is a lyase?
catalyzes the breakdown of chemical bonds by means other than hydrolysis and oxidation
What is a kinase?
transfers phosphate groups from high-energy donor molecules (like ATP) to specific substrates
How does the cell limit substrate cycling between glycolysis and gluconeogenesis?
the two pathways are under reciprocal allosteric control, mainly achieved by the opposing effects of fructose 2,6-bisphosphate on PFK-1 (+) and FBPase-1 (-)
How is gluconeogenesis regulated?
at the level of... pyruvate carboxylase (which is activated by acetyl-CoA) and FBPase-1 (which is inhibited by fructose 2,6-bisphosphate and AMP)
How does glucagon or epinephrine decrease [fructose 2,6-bisphosphate]?
by raising [cAMP] and bringing about phosphorylation of the bifunctional enzyme PFK-2/FBPase-2
How does insulin increase [fructose 2,6-bisphosphate]?
by activating a phosphoprotein phosphatase that dephosphorylates and thus activates PFK-2
Where is the pyruvate dehydrogenase complex found?
located in the mitochondria of eukaryotic cells and in the cytosol of bacteria
In the formation of citrate, where happens to the liberated CoA? (step 1 of CAC)
recycled to participate in oxidative decarboxylation of another molecule of pyruvate by the PDH complex
Why is the large, negative standard free-energy change of the citrate synthase reaction is essential to the operation of the Krebs cycle?
the concentration of oxaloacetate is normally very low
How is the energy of oxidation of alpha-ketoglutarate conserved?
by the formation of the thioester bond of succinyl-CoA
The genes for an enzyme with one substrate specificity give rise, during evolution, to closely related enzymes with different substrate specificities but the same enzymatic mechanism is a clear case of what?
divergent evolution
The formation of ATP (or GTP) at the expense of the energy released by the oxidative decarboxylation of alpha-ketoglutarate is a substrate-level phosphorylation, like the synthesis of ATP in the glycolytic reactions catalyzed by what enzymes?
glyceraldehyde 3-phosphate dehydrogenase pyruvate kinase
What is the net result of the activity of either isozyme of succinyl-CoA synthetase? (step 5 of CAC)
the conservation of energy as ATP there is no change in free energy for the nucleoside diphosphate kinase reaction; ATP and GTP are energetically equivalent
What is the total number of molecules yielded in the citric acid cycle?
2 ATP, 6 NADH, 2 FADH2, 4 CO2, and 6 H+ (this is doubled because of 2 pyruvate molecules)
How many ATP does NADH correspond to?
each NADH yields about 2.5 ATP
How many ATP does FADH2 correspond to?
each FADH2 yields about 1.5 ATP
What are anapldrotic reactions?
reactions that replenish intermediates of the CAC when they are removed to serve as biosynthetic precursors
Who uses the glyoxylate cycle?
germinating seeds of some plants certain microorganisms that can live on acetate as the sole carbon source
What is the function of the glyoxylate cycle?
allows plants and some microorganisms to grow on acetate because the cycle bypasses the decarboxylation steps of the citric acid cycle
Aconitase is considered to be a "moonlighting" protein. What does this mean?
it acts both as an enzyme and as a regulator of protein synthesis
In the presence of oxygen, what is pyruvate converted to?
acetyl-CoA
Lactate dehydrogenase requires continuous supply NADH, which is obtained from what glycolytic step?
conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate by the enzyme glyceraldehyde 3-phosphate dehydrogenase NADH is then oxidized to NAD+ to be used in lactate dehydrogenase
How many molecules of inorganic phosphate are needed for one glucose?
two
What is the role of niacin in glycolysis?
required for the synthesis of NAD+
What is the cost of ATP when transforming glucose to pyruvate and then pyruvate back to glucose?
four (4)
Why is it important that gluconeogenesis is not the exact reversal of glycolysis?
Gluconeogenesis would be highly endergonic because glycolysis is highly exergonic making it very unfavorable. It would also be impossible to separately regulate the two pathways.
Why is the concentration of lactate not zero during the resting state?
cells containing lactate dehydrogenase are always favorable in the synthesis of lactate