2nd Unit / Ch Glycolysis Flashcards
Catabolic Pathways 8.1
What common product of protein, carbohydrate, and fat catabolism is represented by the red question mark?
Acetyl CoA , the common product of protein, carbohydrate, and fat catabolism, is represented.
Catabolic Pathways 8.1
Catabolic pathways are usually oxidative in that their intermediates donate e - . What coenzymes accept the e - ?
The coenzymes that accept the e - from oxidative reactions in catabolic pathways are NAD+ that gets reduced to NADH + H+ and FAD that gets reduced
to FADH2 .
Catabolic Pathways 8.1
How are these coenzymes used in ATP generation required by anabolic pathways?
The coenzymes NADH and FADH 2 will transfer e - to the mitochondrial ETC. As e - move through the ETC, H+ are pumped across the inner mitochondrial membrane. This creates a H+ gradient that is used by ATP synthase to generate the ATP required by anabolic pathways .
Metabolism Regulation 8.2
Upon ligand binding to (and activation of) the receptor, what happens to the trimeric G S protein shown?
Upon ligand binding, a conformational change in the activated receptor (a GPCR ) causes the GDP bound to the
subunit of the trimeric GS protein to be replaced by GTP. The subunit then dissociates from the B and y subunits and stimulates Adenylyl cyclase to produce cAMP. With time, the subunit hydrolyzes the bound GTP to GDP by itsinherent GTPase activity and is inactivated.
Metabolism Regulation 8.2
- What is a second messenger?
- What second messenger is generated by activation of the receptor shown? How does it activate cellular pathways in the cell?
- A second messenger is an intracellularly generated molecule that links the original extracellular message (ligand binding) and the intracellular effects.
- The second messenger generated by activation of the receptor shown is cAMP, which binds to the regulatory
subunits of PKA , causing the release and activation of the catalytic subunits. PKA phosphorylates target proteins, either activating or inactivating them.
Metabolism Regulation 8.2
What is the effect of cholera toxin on G s proteins in intestinal epithelial cells?
Cholera toxin causes ADP ribosylation of th alpha subunit of G s proteins, thereby inhibiting the proteins’ inherent
GTPase activity, which constitutively activates the proteins.
[ Note: PKA phosphorylates and activates the CFTR
protein, a Cl - channel. H2O, Cl- , Na+ , K+ , and HCO3+ are secreted into the intestinal lumen, causing cholera’s
characteristic watery diarrhea and dehydration.]
Glucose Transport and Phosphorylation 8.3
This figure depicts _____ glucose transport through the cell membrane by a GLUT that functions _____as a. The GLUT abundant in muscle and adipose tissue is the insulin-dependent______
This figure depicts facilitated glucose transport through the cell membrane by a GLUT that functions as a uniporter (in that it transports one specific molecule). The GLUT abundant in muscle and adipose tissue is the insulin-dependent GLUT-4.
[Note: Glucose transport by GLUTs is down a concentration gradient. In contrast, SGLTs are energy-requiring transporters that move glucose against its concentration gradient in the intestine, kidney, and choroid plexus.]
Glucose Transport and Phosphorylation 8.3
How does the cell ensure that the glucose taken in by a GLUT remains inside rather than diffusing back out?
Hexokinases irreversibly catalyze the phosphorylation of intracellular glucose to glucose 6-P, thereby trapping it inside the cell because no cell membrane transporter exists for phosphorylated sugars.
[ Note: There are four isoforms of hexokinase . Hexokinases I–III are found in most tissues. Hexokinase IV
( glucokinase ) is found in the liver and pancreatic B cells.]
Glucose Transport and Phosphorylation 8.3
Why might inactivating mutations in glucokinase result in diabetes?
Glucokinase acts as a glucose sensor in pancreatic B cells and helps regulate insulin secretion. Inactivating mutations can impair insulin secretion, resulting in
maturity-onset diabetes of the young ( MODY ). [Note: In contrast to the other hexokinases, glucokinase has a high Km (it functions only when glucoseconcentration is high), a high Vmax (it functions effi ciently when glucose concentration is high), and is not directly inhibited by glucose 6-P.]
Fructose 6-Phosphate Phosphorylation 8.4
What are the positive and negative allosteric effectors of the enzyme PFK- 1 shown at the top of the figure?
AMP and fructose 2,6-bisP are positive allosteric effectors (activators) and ATP and citrate are negative allosteric effectors ( inhibitors ) of PFK-1, the enzyme that irreversibly phosphorylates fructose 6-P.
Fructose 6-Phosphate Phosphorylation 8.4
How does insulin signaling affect the activity of PFK-1?
Insulin signaling activates PFK-1 activity as shown above.
Fructose 6-Phosphate Phosphorylation 8.4
PFK-1 is a tetramer composed of different combinations of L and/or M subunits in different tissues. RBCs express both subunits. Patients with Tarui disease have a genetic defect in the M subunit and display muscle fatigue with exertion and myoglobinuria. What should
be true about the ability of their RBCs to perform glycolysis?
Because any PFK-1 tetramer with an M subunit will be inactive, the RBCs in Tarui disease will contain only one functional form of the enzyme (L 4 ) and will, therefore, have limited ability to perform glycolysis, their sole source of ATP. Impairment of RBC glycolysis leads to hemolysis.
Glyceraldehyde 3-Phosphate Oxidation 8.5
What is the signifi cance of the 2,3-BPG generation shown
2,3-BPG is an important allosteric effector of Hb. It decreases the affinity of Hb for O2 , thereby increasing O2 delivery to tissues. The mutase - catalyzed reaction that produces 2,3-BPG occurs to a
significant extent only in RBCs.
Glyceraldehyde 3-Phosphate Oxidation 8.5
What is the fate of the NADH generated by glyceraldehyde 3-P oxidation?
The NADH generated by glyceraldehyde 3-P oxidation is either oxidized by LDH as pyruvate is reduced to lactate, or its reducing equivalents are shuttled to the mitochondrial ETC. [Note: In skeletal muscle, NADH production during intense exercise can exceed ETC oxidative capacity, resulting in an elevated NADH/NAD ratio that favors lactate production.]
Glyceraldehyde 3-Phosphate Oxidation 8.5
How can arsenate (pentavalent arsenic) poisoning prevent net ATP production by glycolysis without inhibiting the pathway itself?
Arsenate can compete with Pi as a substrate for glyceraldehyde 3-P dehydrogenase, forming a complex that spontaneously hydrolyzes to produce 3-phosphoglycerate. Consequently, the substrate-level phosphorylation reaction of glycolysis catalyzed by phosphoglycerate kinase is bypassed, decreasing the net yield of ATP from the pathway without inhibiting the pathway itself.
Pyruvate Kinase 8.6
What pancreatic hormone bound to its receptor causes the cascade of events shown?
The pancreatic hormone is glucagon. Binding to its GPCR initiates the cascade that results in phosphorylation and inactivation of the hepatic isoform of PK .
[Note: A protein phosphatase can remove the phosphate group and reactivate PK .]
