Biochem Ch 17-19 (Gluconeogenesis, TCA cycle)

gluconeogenesis

synthesis of glucose from noncarbohydrate sources

examples of noncarbohydrate sources

lactate, amino acids, glycerol

contrast gluconeogenesis and glycolysis

gluconeogenesis requires 4 new rxns to bypass the irreversibility of 3 rxns in glycolysis

in 2 of these new rxns, pyruvate is carboxylated

in mitochondria to oxaloacetate

oxaloacetate îs then decarboxylated and phosphorylated

in cytosol to phosphoenolpyruvate

in the 2 new reactions involving pyruvate

2 high energy phosphate bonds are consumed

the 2 high energy phosphate bonds are catalyzed by

pyruvate carboxylase and phosphoenolpyruvate carboxykinase

what are the other 2 distinctive reactions of gluconeogenesis

hydrolyses of fructose 1,6-biphosphate and G6P

lactate that is generated by glycolysis in contracting muscle is released

into the bloodstream

lactate in the bloodstream is then

removed from the blood by liver and converted into glucose by gluconeogenesis

the metabolic cooperation b/w muscle and liver is called

Cori cycle

the formation of lactate during intense muscular activity

buys time and shifts part of metabolic burden from muscle to liver

gluconeogenesis and glycolysis are reciprocally regulated. what does this mean?

one pathway is relatively inactive while the other is highly active

what are the key control points

phosphofructokinase and fructose 1,6-biphosphatase

when is fructose 2,6-biphosphate present

at higher levels when glucose is abundant

purpose of fructose 2,6-biphosphate

an intracellular signal molecule that activates glycolysis and inhibits gluconeogenesis

how does fructose 2,6-biphosphate fulfill its role

by regulating the key control point enzymes

pyruvate kinase, pyruvate carboxylase, and phosphoenolpyruvate carboxykinase are regulated by

other effectors that reflect cellular energy, to ensure only one pathway is active at any moment

T/F allosteric regulation and reversible phosphorylation are slow

false

allosteric regulation and reversible phosphorylation are complemented by

transcriptional control, taking hours or days

the citric acid cycle is also referred to as the

tricarboxylic acid cycle

what is the citric acid cycle

the final common pathway for the oxidation of fuel molecules

the citric acid cycle serves as a source of

building blocks for biosynthesis

most fuel molecules enter the cycle as

acetyl CoA

the link between glycolysis and the citric acid cycle is

oxidative decarboxylation of pyruvate to make acetyl CoA

in eukaryotes, the TCA rxns take place in

the mitochondria

the decarboxylation of pyruvate to make acetyl CoA generates how many NADH

one

the PDH complex consists of

3 distinct enzyme activities that require 5 cofactors

what does the TCA cycle begin with

condensation of oxaloacetate and acetyl CoA to give citrate, then isomerized to isocitrate

second, oxidative decarboxylation of the intermediate gives

a-ketoglutarate

third, the 2nd molecule of CO2 comes off, and a-ketoglutarate

is oxidatively decarboxylated to succinyl CoA

fourth, the thioester bond of succinyl CoA is cleaved to yield

succinate and generate a GTP

fifth, succinate is oxidized to

fumarate

sixth, fumarate is hydrated to

form malate

lastly, malate is oxidized to

regenerate oxaloacetate

___ carbon atoms from acetyl CoA leave and enter the TCA

2

___ carbon atoms leave TCA as CO2

2

the 2 carbons leaving TCA cycle are catalyzed by

isocitrate dehydrogenase and a-ketoglutarate dehydrogenase

in the 4 oxidation-reduction rxns in the TCA cycle

3 pairs of electrons are transferred to NAD+, one pair to FAD

these reduced electron carriers are

oxidized by electron transport chain to generate 9 ATP

how many GTP directly formed in citric acid cycle

1

for each 2 carbon fragment completely oxidized to H20 and CO2, how many molecules are generated

10

why is the TCA cycle aerobic

requires a supply of NAD+ and FAD

NAD+ and FAD are regenerated when

NADH and FADH2 transfer electrons to O2 through ETC

the rate of TCA cycle depends on

need for ATP

purpose of formation of acetyl CoA from pyruvate

important regulatory point of entry for glucose-derived pyruvate into TCA cycle

T/F the formation of acetyl CoA form pyruvate is irreversible

true

pyruvate dehydrogenase complex is

allosterically inhibited by acetyl CoA and NADH

the activity of the PDH complex is controlled through

reversible phosphorylation by associated kinase and phosphatase

high concentrations of ____ stimulate the PDH kinase

ATP, NADH, acetyl-CoA

ATP, NADH and acetyl-CoA purpose in PDH kinase

phosphorylate and inactivate the kinase

ADP and pyruvate

inhibit the PDH kinase

Ca2+ stimulates the phosphatase, which then

desphosphorylates and activates teh complex

in the liver, epinephrine

activates the PDH phosphatase

in both the liver and adipose tissues, insulin

stimulates PDH phosphatase, increasing conversion of pyruvate into acetyl CoA

purpose of insulin

hormone that signifies fed state

in these tissues, PDH complex is activated to

funnel glucose ro pyruvate, acetyl CoA, then FAs

in eukaryotes, NADH diminishes the activities of

isocitrate dehydrogenase and a-ketoglutarate dehydrogenase

a-ketoglutarate dehydrogenase is inhibited by

succinyl-CoA

isocitrate dehydrogenase is stimulated by

ADP

the regulatory mechanisms complement each other by

reducing the rate of formation of acetyl CoA

the rate of formation of acetyl CoA is reduced when

energy charge of cell is high and biosynthetic intermediates are abundant

when the cell has adequate energy available the TCA cycle

can provide source of building blocks for biomolecules, such s nucleotide bases, proteins, heme groups

by providing building blocks for biomolecules, the cycle of intermediates

is depleted

the cycle intermediates are replenished by

anaplerotic reactions