Gluconeogenesis

Question 1

what happens if glucose level in our body is low

Question 2

examples of tissues that require glucose

Answer 2

brain
RBC
kidney medulla
lens and cornea
testes
exercising muscle

Question 3

which tissues synthesise glucose

Answer 3

liver (90%) and kidney (10%)

Question 4

what are precursors of glucose

Answer 4

lactate
pyruvate
glycerol
glucogenic amino acids - alanine

Question 5

what are sources of precursors of glucose

Answer 5

diet
liver/muscle glycogen store

Question 6

what results after glycogen reserves are exhausted in starvation

Answer 6

breakdown of muscle proteins to glucogenic amino acids
around 30% in the form of alanine

Question 7

where does oxaloacetate synthesis for gluconeogenesis exclusively occur

Answer 7

mitochondrion

Question 8

in which type of cells must oxaloacetate be transported through one of two routes to the cytosol

Answer 8

cytosolic-exclusive PEPCK cells
cells which contain PEPCK in the cytosol only and not in the mitochondria also

Question 9

what are the two routes though which oxaloacetate can cross the mitochondrial membrane

Answer 9

conversion to either malate or aspartate
transport via transporter protein
conversion back to oxaloacetate

Question 10

which enzyme converts between oxaloacetate and malate

Answer 10

malate dehydrogenase

Question 11

which enzyme converts between aspartate and oxaloacetate

Answer 11

aspartate aminotransferase

Question 12

what type of acids cannot be used for gluconeogenesis

Answer 12

fatty acids
e.g. acetyl CoA

Question 13

what are the three steps of glycolysis that are different in glycolysis and gluconeogenesis

Answer 13

glucose -> G6P
F6P -> FBP
PEP -> pyruvate

Question 14

G6P -> glucose enzyme

Answer 14

glucose-6-phosphatase

Question 15

FBP -> F6P enzyme

Answer 15

FBPase

Question 16

pyruvate -> PEP enzymes

Answer 16

pyruvate carboxylase then PEP carboxyl kinase (PEPCK)

Question 17

why is alanine an inhibitor of glycolysis

Answer 17

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something to do with its use in gluconeogenesis

Question 18

what is the first layer of regulation of gluconeogenesis

Question 19

what is secondary level of regulation of gluconeogenesis

Question 20

why is PFK the major flux-controlling enzyme in muscle

Question 21

why is phosphofructokinase 1 the major flux controlling enzyme in muscle

Question 22

how is phosphofructokinase 1 regulated by allosteric modulators
which states does each bind

Answer 22

ATP (upstream substrate) binds exclusively in T-state preventing F6P binding
F6P (substrate) bind exclusively in R state
AMP (downstream product) binds R-state preferentially and counters inhibitory effect of T-state

Question 22

what is the first committed step of glycolysis and why

Question 23

T-state vs R-state of PFK

Answer 23

T- ‘tense’ and R- ‘relaxed’
relaxed in active form of the enzyme
refers to active site, relaxed is more open and favours substrate binding
two ATP binding sites: one substrate and one inhibitor (exposed only in T-conformation)

Question 24

effect of insulin

Answer 24

causes activation of PKA, stimulating glycolysis pathway

Question 25

effect of glucagon

Answer 25

causes phosphorylation of glycolysis pathway enzymes (inactivates)
increases gluconeogenesis pathway