Lecture Exam 1

Question 1

What is a beta-granule? What protein is at the core?

Answer 1

-Beta Granule: cytosolic granules that vary in size, structure, and subcellular location that appear as electron-dense particles
-Glycogenin is the protein at the core

Question 2

What forms the initial primer for glycogen?

Answer 2

Glycogenin

Question 3

What enzymes are involved in building glycogen and what are their roles?

Answer 3

-Phosphoglucomutase: converts glucose-6-phosphate into glucose-1-phosphate
-UDP-glucose pyrophosphorylase: converts glucose 1-phosphate to UDP-glucose
-Glycogenin: the primer on which new chains are assembled and the enzyme that catalyzes the assembly of glycogen
-Glycogen Synthase: catalyzes the transfer of the glucose residue from UDP-glucose to a nonreducing end of a branched glycogen molecule, forming an alpha 1-4 linkage
-turned on when dephosphorylated by PP1; turned off when phosphorylated
-Glycogen Branching enzyme: catalyzes the formation of tha alpha 1-6 bonds found at the branch points of glycogen

Question 4

What factors/hormones regulate the synthesis of glycogen? How does this differ between the liver and the muscle?

Answer 4

-Liver:
-High Blood Sugar: insulin is high; glycogen synthesis increases; glycogen breakdown decreases; increase PP1; decrease GSK-3
-Low Blood Sugar: decrease Glycogen Synthase; decrease glycogen synthesis; increase FBPase-2
-Muscle:
-Insulin: increase glycogen synthesis
-Glucagon: increases release of glucose (primarily acts on liver)
-Epinephrine: activates glycogenolysis to provide ATP
-The liver will shut down glycolysis if they dont need energy, but the muscle will not

Question 5

What enzymes are involved in breaking down glycogen? What are their roles?

Answer 5

-Glycogen Phosphorylase: catalyzes phosphorylytic cleavage at the nonreducing ends of glycogen chains
-Debranching Enzyme: transfers branches onto main chains and releases the residue at the alpha 1-6 branch as free glucose
-Phosphoglucomutase: converts glucose-1-phosphate into glucose-6-phosphate

Question 6

What happens to glucose released from glycogen in muscle vs. liver?

Question 7

What factors/hormones regulate glycogen break down? How does this differ between the liver and the muscle?

Question 8

How do CKII and GSK3 cooperate to activate glycogen synthase?

Answer 8

-GSK3 cannot phosphorylate glycogen synthase until casein kinase II has phosphorylated the glycogen synthase on a nearby residue (a priming event)

Question 9

What is phosphoprotein phosphatase 1 (PP1) and what is its role in regulating glycogen metabolism?

Answer 9

-PP1: removes phosphoryl groups from phosphorylase a, converting it to the less active form, phosphorylase b; also inactivates Glycogen Synthase b by adding a phosphate to glycogen synthase a

Question 10

What does the pyruvate dehydrogenase complex (PDH) do? Where is it located?

Answer 10

-PDH oxidizes pyruvate to acetyl-CoA and CO2
-It is located in the mitochondrial matrix

Question 11

What coenzymes are used by the PDH?

Answer 11

-Thiamine pyrophosphate (TPP)
-Lipoate
-Coenzyme A (CoA, CoA-SH)
-Flavin adenine dinucleotide (FAD)
-Nicotinamide adenine dinucleotide (NAD)

Question 12

What are the roles of the E1, E2, and E3 enzymes of the PDH?

Answer 12

-E1 enzyme: pyruvate dehydrogenase, E1, with bound TPP catalyzes:
step 1: decarboxylation of pyruvate to the hydroethyl derivate rate-limiting step step 2: oxidation of the hydroethyl derivate to an acetyl group electrons and the acetyl group are transferred from TPP to the lipoyllysyl group of E2
-E2 enzyme: dihydrolipoyl transacetylace catalyzes Step 3: esterification of the acetyl moiety to one of the lipoyl-SH groups, followed by transesterification to CoA to form acetyl-CoA
-E3 enzyme: catalyzes Step 4: electron transfer to regenerate the oxidized form of the lipoyllysyl group; Step 5:electron transfer to regenerate the oxidized FAD cofactor, forming NADH

Question 13

What does the citric acid cycle do? What purpose does it play in energy generation?

Answer 13

-Citric Acid Cycle: a hub of metabolisim, with catabolic pathways leading in and anabolic pathways leading out. Oxidation of acetyl groups to CO2; nearly universal pathway that generates NADH, FADH2, and one GTP

Question 14

What are the irreversible steps of the citric acid cycle?

Answer 14

-Step 1: Formation of Citrate
-Step 3: Oxidation of Isocitrate to alpha Ketoglutarate and CO2
-Step 4: Oxidation of alpha ketoglutarate to succinyl-CoA and CO2

Question 15

What are the products and outputs from the pathway (in terms of energy and reduced cofactors) per round? Which steps do they come from?

Answer 15

-3 NADH→produced in step 3, 4, and 8 (one per step)
-1 FADH2→produced in step 6
-1 ATP→produced in step 5

Question 16

Why do the textbook authors use gene duplication and divergent evolution to explain similarities between metabolic pathways (like slide 34)?

Answer 16

-pathways use the same five cofactors, similar multienzyme complexes, and the same enzymatic mechanism
-have homologous E1 and E2, and identical E3

Question 17

How much ATP is generated from the citric acid cycle alone versus glycolysis?

Answer 17

-The citric acid cycle forms only one ATP per turn, while glycolysis forms 4 ATP (2 net) per turn.

Question 18

What are antipleuritic reactions? Why is the citric acid cycle called amphibolic?

Answer 18

-Antipleuritic reactions: Chemical reactions that replenish intermediates
-Amphibolic Pathway: one that serves in both catabolic and anabolic processes
-The Citric Acid Cycle is an amphibolic pathway because it has both catabolic and anabolic pathways

Question 19

What biomolecule anabolic pathways are fed by components of the citric acid cycle?

Answer 19

-Fatty acids and sterols are fed by citrate
-alpha ketoglutarate feeds into glutamate, which feeds purines and different amino acids
-Succinyl-CoA feeds into porphryins and heme
-Oxaloacetate feeds into Asparate and Asparigine to make pyrimadines

Question 20

How does pyruvate carboxylase help when acetyl-CoA levels build up?

Answer 20

-Pyruvate Carboxylase: catalyzes the reversible carboxylation of pyruvate by HCO3- to form oxaloacetate
-it is allosterically activated by acetyl-CoA

Question 21

What are the main points of regulation from the PDH through the citric acid cycle? What factors inhibit or promote those points?

Answer 21

-Main Points of Regulation:
-PDH Complex
-Citrate Synthase
-isocitrate dehydrogenase complex
-alpha-ketoglutarate dehydrogenase complex
-Inhibiting or Promoting:
-Inhibiting PDH: ATP, acetyl-CoA,NADH, fatty acids
-Activating PDH: AMP, CoA, NAD+, Ca2+
-Inhibiting Citrate Synthase: NADH, succinyl-CoA, citrate, ATP
-Activating Citrate Synthase: ADP
-Inhibiting isocitrate dehydrogenase complex: ATP
-Activating isocitrate dehydrogenase complex: Ca2+, ADP
-Inhibiting alpha-ketoglutarate: succinyl-CoA, NADH
-Activating alpha-ketoglutarate dehydrogenase complex: Ca2+

Question 22

What does beta oxidation do? What are the products of the process? Where does it occur?

Answer 22

-Beta Oxidation: oxidation of the fatty acid group at the C-3, or Beta position-hence the name
-Products: 8 acetyl-CoA, 7 FADH2, 7 NADH, 7H+
-Occurs after the carboxyl group at C-1 is activated by attachment to coenzyme A

Question 23

How are dietary fats absorbed? What happens to triacylglycerols in the gut and where do the components go when they get absorbed?

Answer 23

-Dietary Fats are absorbed in the small intestine
-Triacylglycerols are degraded by intestinal lipases and the components go into chylomicrons, which travel through the body until they convert to fatty acids and monoacylglycerols

Question 24

What is a chylomicron? Where is it formed? Where does it go?

Answer 24

-Chylomicrons: particles consisting of triacylglycerols, cholesterol, and apolipoproteins
-They are formed in intestinal cells
-They move through the lymphatic system and bloodstream to get to the tissues

Question 25

What are apolipoproteins and lipoproteins?

Answer 25

-Apolipoproteins: proteins in their lipid free form that bind lipids to form lipoproteins
-target triacylglycerols, phospholipids, cholesterol, and cholesteryl, and cholesterol esters for transport between organs
-Lipoproteins: spherical aggregates of apolipoproteins and lipids
-arranged with hydrophobic lipids at the core and hydrophilic protein side chains and lipid head groups at the surface
-various in densities depending on combinations of lipid and protein

Question 26

What does lipoprotein lipase do and where does it do it?

Answer 26

-Lipoprotein Lipase: extracellular enzyme in the capillaries of muscle and adipose tissue that hydrolyzes triacylglycerols to free fatty acids and monoacylglycerols
-It works in the capillary

Question 27

Where are excess fatty acids stored in the body? What form are the molecules in?

Answer 27

-Excess fatty acids are converted to triacylglycerols in the liver; then the triacylglycerold are removed and stored in lipid droplets within adipocytes in the adipose tissue

Question 28

What is the role of serum albumin?

Answer 28

-Serum Albumin: blood protein that noncovalently binds and transports FFAs to target tissues

Question 29

What happens to glycerol when the fatty acid tails are removed? (ie, what metabolic pathway can it feed into?

Answer 29

-When the fatty acid tail is removed by glycerol kinase, it converts into glycerol 3-phosphate. That can enter glycolysis

Question 30

What molecule is used to shuttle fatty acids into the mitochondrial matrix? What enzymes are involved in this? What controls this?

Answer 30

-acyl-carnitine/carnitine cotransporter: allows the passive transport of the fatty acyl-carnitine ester
-moves one carnitine into the intermembrane space as one fatty-acyl-carnitine moves into the matrix
-carnitine acyltransferase 1 controls this

Question 31

What are the four basic steps in beta oxidation? What other reaction pathways have similar steps?

Answer 31

Stage 1: fatty acids undergo oxidative removal of successive two-carbon units in the form of acetyl-CoA
Stage 2: oxidation of acetyl-CoA groups to CO2 in the citric acid cycle
Occurs in mitochondrial matrix
Generates NADH, FADH2, and one GTP
Stage 3: electron transfer chain and oxidative phosphorylation; generates ATP from NADH and FADH2
Stage 4: electros from fatty acyl-CoA enter the mitochondrial respiratory chain???

Question 32

Where do the acetyl-CoA from beta oxidation go? How much energy can be produced from them?

Answer 32

-Acetyl-CoA generated by the beta-oxidation pathway enters the mitochondrial TCA cycle, where is further oxidized to generate NADH and FADH2
-I found this on google because I couldnt find anything about it

Question 33

How are unsaturated fats oxidized?

Answer 33

-Oxidation of a monounsaturated fatty acid requires an enoyl-CoA isomerase
-Double bonds have to be trans because beta oxidation doesn’t work on cis

Question 34

What is proprionate and why is it produced?

Answer 34

-Propionate: three-carbon compounds formed by cattle and other ruminant animals during carbohydrate fermentation

Question 35

What are the regulation points of fatty acid oxidation?

Answer 35

-Malonyl-CoA= the first intermediate of cytosolic fatty acid synthesis
-blocks entry of fatty acids into mitochondria to prevent futile cycling

Question 36

When is the peroxisomal fatty acid oxidation pathway used?

Answer 36

-Peroxisomal fatty acid oxidation is used on very-long-chain fatty acids and branched-chain fatty acids

Question 37

What are ketone bodies and when are they produced?

Answer 37

-Ketone Bodies: acetone, acetoacetate, and D-beta-hydroxybutyrate are formed from acetyl-CoA in the liver

Question 38

How are ketone bodies used?

Answer 38

-acetone is exhaled
-acetoacetate andD-β-hydroxybutyrate are transported to extrahepatic tissues
and converted to acetyl-CoA to be oxidized inthe citric acid cycle

Question 39

What is ketosis and ketoacidosis?

Answer 39

-Ketosis: high levels of ketone bodies in the blood and urine
-Ketoacidosis: condition when ketosis and acidosis are combined