3: Glycolysis & Glycogen Flashcards
Describe the types of reactions catalyzed and the strategies employed during the 10-step glycolytic pathway that converts one glucose to two pyruvate
Hexokinase phosphorylates Glu to give G6P. Glucokinase in liver has less affinity. G6P is trapped in the cell since it has no transporter. Glycolysis occurs in the cytosol of the cell. 1 ATP used.
G6P -> F6P. Enzyme: Phosphoglucoisomerase.
F6P + 1 ATP -> F1,6BF. Enzyme: Phosphofructokinase. This is a key **regulation step.
Aldolase cleaves F1,6BF into DHAP + G3P (glyceraldehyde 3 phosphate). Next, DHAP will be converted to G3P by triose isomerase.
Up to this point, we invested 2 ATP.
G3P -> 1,3BPG by G3P dehydrogenase.
1,3 Biphosphoglycerate -> 3 phosphoglycerate + 2 ATP by phosphoglycerate kinase. We’re now even for the ATP used by Hexokinase and Phosphofructokinase. This is an example of Substrate-level Phosphorylation
3 phosphoglycerate -> 2 phosphoglycerate by phosphoglycerate mutase
2 phosphoglycerate -> phosphoenolpyruvate by enolase
phosphoenolpyruvate -> pyruvate + 1 ATP/ pyruvate (2 net) by pyruvate kinase. The PK reaction is another example of Substrate-level Phosphorylation
NOTE: Substrate-level phosphorylation is a type of metabolic reaction that results in the formation of adenosine triphosphate (ATP) or guanosine triphosphate (GTP) by the direct transfer and donation of a phosphoryl (PO3) group to adenosine diphosphate (ADP) or guanosine diphosphate (GDP) from a phosphorylated reactive intermediate.
Discuss the mechanism of the enzymes in the glycolytic pathway with regard to the amino acid residues, coenzymes, and cofactors that participate in their reactions
Hexokinase/ glucokinase =
Phosphofructokinase =
Glyceraldegyde 3 phosphate dehydrogenase =
Phosphoglycerate kinase =
phosphoglycerate mutase =
Pyruvate kinase =
Hexokinase/ glucokinase = ATP
Phosphofructokinase = ATP
Glyceraldegyde 3 phosphate dehydrogenase = NAD+ & Acyl thioester
Phosphoglycerate kinase = ADP
phosphoglycerate mutase = phosphohistidyl intermediate
Pyruvate kinase = ADP
Identify the steps that involve the use and production of ATP, and quantitate the net gain in ATP achieved by the glycolytic pathway
Invest 1 ATP:
hexokinase
Phosphofructokinase
Generation of ATP:
2 ATP phosphoglycerate kinase
2 ATP purvate kinase
Net gain of two ATP and two NADH in converting Glu to two Pyr.
Describe the fate of glycolytic NADH under both aerobic and anaerobic conditions
Under aerobic conditions, glycolytic NADH (2 of them) is indirectly oxidized by oxidative phosphorylation and pyruvate enters the TCA cycle
Under anaerobic conditions, pyruvate is reduced by glycolytic NADH via lactate dehydrogenase to give lactate
Describe how fructose, mannose and galactose enter the glycolytic pathway
Galactose becomes G6P
Mannose & muscle Fructose become F6P
Hexokinase (but not liver glucokinase) converts Fructose to F6P
Galactose involves Galactokinase, a UMP Transferase, an Epimerase, and Phosphoglucomutase
Describe the types of reactions catalyzed during the synthesis and breakdown of glycogen
Glycogen synthesis:
G6P -> G1P by phosphoglucomutase
G1P -> UDP-Glucose by UDP glucose phosphorylase
UDP-Glucose -> Glycogen by Glycogen synthase & Branching enzyme. Glycogen is a branched polymer.
Glycogen breakdown:
Glycogen -> G1P by Debranching enzyme & glycogen phosphorylase
G1P -> G6P by phosphoglucomutase
Glycolysis
Recognize the special role played by liver glycogen in maintaining blood glucose
Liver glycogen can release glucose into the blood or store glucose in the liver depending on the body’s needs.
Calculate the cost of temporarily storing a glucose-6-P molecule as a unit in a glycogen polymer when you begin with glucose-6-P and end with glucose-6-P to be used as a substrate for glycolysis.
The cost if you’re going to use the released G6P for glycolysis is 1 UTP → UDP + Pi per G6P temporarily stored, plus 0.1 ATP/Glu to rephosphorylate the 10% of the Glu units released by hydrolysis of the α(1-6)glycosidic bond at branch points, for a total of 1.1 ATP/G6P stored
Calculate the cost of temporarily storing a glucose molecule as a unit in a glycogen polymer when you begin with glucose just taken up from the blood stream and you end with glucose about to be released back into the blood stream.
The cost in liver cells when blood Glu is taken up, stored, and then released back into the blood stream is 1 ATP used by Glucokinase, plus 1 UTP used by the UMP transferase, or an equivalent of 2 ATP per blood Glu temporarily stored in the liver
Type I Von Gierke disease
Defective: Glucose-6-phosphatase or transport system. Glucose 6-phosphatase hydrolyzes glucose-6-phosphate, resulting in the creation of a phosphate group and free glucose. Glucose is then exported from the cell via glucose transporter membrane proteins.This catalysis completes the final step in gluconeogenesis and glycogenolysis–IT RELEASES GLUCOSE.
Organs affected: Liver and kidney
Glycogen in the organs: increases
Clinical features: Massive enlargement of the
liver. Failure to thrive. Severe hypoglycemia, ketosis, hyperuricemia, hyperlipemia.
Type IV Anderson disease
Defective: Branching enzyme (α-1,4 → α-1,6)
Organs affected: Liver and spleen
Glycogen in the organs: Normal amount; very long outer branches.
Clinical features: Progressive cirrhosis of the liver. Liver failure causes death, usually before age 2.
Type V McArdle disease
Defective: Phosphorylase
Organ affected: Muscle
Glycogen in the organ: Moderately increased amount, normal structure.
Clinical features: Limited ability to perform strenuous exercise because of painful muscle cramps. Otherwise patient is normal and well developed. People usually find out when they do high school sports.
