Biochem Exam 2: Gluconeogenesis

Front 1

Why can't muscle do gluconeogenesis?

Back 1

It lacks 2 essential enzymes:

-pyruvate carboxylase

-glucose 6 phosphatase

Front 2

Pyruvate carboxylase requires ____________ as a cofactor.

Back 2

biotin

Front 3

What three things does the liver use to synthesize glucose?

Back 3

-amino acids
-glycerol
-lactate

Front 4

Where does most lactate come from?

Back 4

exercising muscle and RBC's

(also comes from skin, lens and cornea)

Front 5

What enzyme turns lactate to pyruvate for gluconeogenesis?
What would a deficiency in this enzyme lead to?

Back 5

lactate dehydrogenase

muscle cramping and myoglobinuria after intense exercise

Front 6

What enzyme converts alanine to pyruvate for gluconeogenesis?

Back 6

alanine aminotransferase

Front 7

What enzyme converts aspartate into a usable intermediate of gluconeogenesis?

Back 7

aspartate aminotransferase converts aspartate into a TCA intermediate which turns into OAA

Front 8

What enzyme converts glutamate into a usable intermediate of gluconeogenesis?

Back 8

glutamate dehydrogenase turns glutamate into a TCA intermediate which turns into OAA

Front 9

For use in gluconeogenesis, glycerol must first be converted into ______________ and then into ____________.

Back 9

-glycerol 3 phosphate

-DHAP

Front 10

What enzyme converts glycerol into glycerol 3 phosphate?

Back 10

glycerol kinase (it adds a P)

Front 11

What enzyme converts glycerol 3 phosphate into DHAP?

Back 11

glycerol 3P dehydrogenase

Front 12

First step of gluconeogenesis: what enzyme converts pyruvate...and what does it convert it into?

Back 12

pyruvate carboxylase converts pyruvate into OAA

Front 13

2nd step of gluconeogenesis: what enzyme converts OAA...and what does it convert it into?

Deficiency in this enzyme leads to what?

Back 13

phosphoenolpyruvate carboxykinase converts OAA into PEP

cerebral atrophy, fatty liver and kidney, intractable hypoglycemia

Front 14

What enzyme converts fructose 1,6 bisphospate into fructose 6 phosphate?

Back 14

fructose 1,6 bisphosphatase

Front 15

What enzyme converts glucose 6 phosphate into glucose?

Back 15

glucose 6 phosphatase

Front 16

What enzyme converts fructose 6 phosphate to glucose 6 phosphate?

Back 16

the same one in glycolysis (phosphoglucose isomerase)

Front 17

What are the 2 main regulators of gluconeogenesis?
Which one is the activator and which the inhibitor?

Back 17

glucagon=low energy=activator
insulin=well fed=inhibitor

Front 18

What allosterically regulates fructose 1,6 biphosphatase?

Back 18

fructose 2,6 biphosphate

Front 19

PFK-2 creates ___________, which can allosterically inhibits ____________. This inhibits gluconeogenesis.

Back 19

-fructose 2,6 biphosphate

-fructose 1,6 biphosphatase

Front 20

Fructose 2, 6 biphosphatase converts __________________ into _________________ in the presence of glucagon (low energy)

Back 20

fructose 2,6 biphosphate into fructose 6 phosphate, which can be used in gluconeogenesis

Front 21

If you have an increase in F6P and a decrease in F-2,6-BP, what happens to the metabolic pathways? What hormone stimulates this?

Back 21

If you have an increase in F6P (low F-2,6-BP), you are trying to make/spare glucose. Glycolysis downgraded, gluconeogenesis activated, lipolysis activated.

CAUSED BY GLUCAGON

Front 22

When you have a secretion of insulin, what happens F6P/F-2,6-BP and the metabolic pathways?

Back 22

you have excess glucose that needs to be stored. so fructose 6 phosphate will turn into F-2,6-BP to activate glycolysis and inhibit gluconeogenesis. Lipogenesis and glycogenesis will be activated to store excess glucose

Front 23

Pyruvate carboxylase needs high levels of _____________ to work, as this compound allosterically activates it. Thus, activateing gluconeogenesis.

Back 23

acetyl CoA

Front 24

What compound inhibits pyruvate dehydrogenase?

Back 24

pyruvate dehydrogenase converts pyruvate into acetyl CoA...so the product, acetyl CoA, will inhibit pyruvate dehydrogenase (feedback inhibition)

Front 25

How do you turn off pyruvate kinase?

Back 25

phosphorylation by protein kinase A

Front 26

PEP carboxykinase is activated by ____________________ and is inhibited by_____________.

Back 26

-activated by glucagon, epinepherine, glucocorticoids

-inhibited by insulin

Front 27

How many ATP and pyruvate do you need to synthesize one molecule of glucose in gluconeogenesis?

Back 27

6 ATPs
2 pyruvates

Front 28

PFK-2 activates _____________ and inhibits __________.

Back 28

-activates glycolysis

-inhibits gluconeogenesis by inhibiting fructose 1,6 biphosphatase.

Front 29

PFK-1 and PFK-2 both ___________ glycolysis.

Back 29

activate

Front 30

What 3 steps in glycolysis are irreversible and therefore must be circumvented in gluconeogenesis?

Back 30

1. glucose--> glucose 6 phosphate (via hexokinase/glucokinase)
2. F-6-P --> F-1,6-BP (via PFK-1)
3. PEP--> pyruvate (via pyruvate kinase)

Front 31

In gluconeogenesis, what enzyme is used instead of hexokinase/glucokinase?

Back 31

G-6-Pase

G-6-P --> Glucose

Front 32

in gluconeogenesis, what enzyme is used instead of PFK-1?

Back 32

F-1,6-BPase

F-1,6-BP--> F-6-P

Front 33

Deficiency of F-1,6-BPase leads to what symptoms?

Back 33

neonatal hypoglycemia, acidosis, hypotonia, and moderate hepatomegaly

Front 34

in gluconeogenesis, what enzyme is used instead of pyruvate kinase?

Back 34

pyruvate carboxylase, then PEP carboxylase

pyruvate--> OAA--> PEP

Front 35

G-6-Pase deficiency results in the accumulation of what? leading to what symptoms?

Back 35

accumulation of G-6-P

leads to hepatomegaly, severe hypoglycemia causing lethargy, seizures, brain damage, increased bleeding and growth retardation

Front 36

How does the cori cycle use lactate from muscles for gluconeogenesis even though gluconeogenesis cannot occur in muscles?

Back 36

pyruvate produced from glycolysis in muscle is converted to lactate, then transferred to blood stream where it is taken to liver, in liver lactate is converted to pyruvate which undergoes gluconeogenesis producing glucose, glucose is then transferred to blood stream and taken to muscle where process begins again (glycolysis)

Front 37

Why is glycerol the least desirable carbon source for gluconeogenesis?

Back 37

too many steps, glycerol is released from adipose tissue after triglycerides are degraded to FAs and glycerol by action of hormone-sensitive lipase (not readily available for gluconeogenesis)

Front 38

Hormone sensitive lipase is inhibited by what?

Back 38

insulin (high energy)

Front 39

Biotinidase deficiency is a disorder where _____ is not recycled, causing multiple carboxylase deficiencies. What are some of the most recognizable symptoms?

Back 39

biotin

seizures and hypotonia followed by hearing and vision loss, alopecia, ataxia, skin rashes, candidasis

Front 40

Decreased production of insulin leads to what disease characterized by hyperglycemia caused by low glucose uptake and increased glucose output in liver

Back 40

type I diabetes mellitus

Front 41

Glucose utilization in muscle is limited by what?

Back 41

Low GLUT-4
high acetyl CoA (PDH inhibition)--> lactate production

Front 42

Pyruvate kinase
inhibited/activated/induced by what?

Back 42

inhibited: ATP, alanine, phosphorylation (glucagon & epi -->increase cAMP--> activates PKA-->phosphorylates)
activated: F 1,6-BP

Front 43

Glucokinase
inhibited/activated/induced by what?

Back 43

activated: high glucose
induced: insulin

Front 44

Phosphofructokinase-1 (PFK-1)
inhibited/activated/induced by what?

Back 44

inhibited: ATP, citrate
activated: F 2,6-BP, AMP

Front 45

Pyruvate carboxylase
inhibited/activated/induced by what?

Back 45

activated: acetyl-CoA

Front 46

PEP carboxylase
inhibited/activated/induced by what?

Back 46

induced: glucagon, epinephrine, glucocorticoids

Front 47

G-6-Pase
inhibited/activated/induced by what?

Back 47

induced: fasting (low glucose)

Front 48

F 1,6-BPase
inhibited/activated/induced by what?

Back 48

induced: fasting (low glucose)

Front 49

If glucose levels remain high what will happen?

Back 49

water released from tissues leading to dehydration which causes tissue malfunction and eventual brain dehydration that develops into hyperosmolar coma

Front 50

if glucose drops suddenly what will happen?

Back 50

ATP production in brain decreases leading to dizziness, drowsiness, coma

(normal glucose around 100 mg/dL)

Front 51

if ATP production in RBC's is low what will happen?

Back 51

hemolysis-->tissue hypoxia

Front 52

what causes type 2 diabetes mellitus?
what does it lead to?

Back 52

decrease in insulin release or sensitivity to insulin results in hyperglycemia

Front 53

After a carbohydrate (glucose) rich meal, what will happen to glucose, insulin, and glucagon levels?

how does this vary from a protein rich meal?

Back 53

carb rich meal: slight glucose increase, large insulin spike, small glucagon increase followed by larger drop

protein rich meal: glucose unchanged, slight insulin increase, slight glucagon increase

Front 54

Why does glucagon increase after a protein rich meal?

Back 54

glucagon is used to trigger lipolysis and gluconeogenesis

Front 55

During fasting _____ and _____ are low in blood and _____ is high.

Back 55

glucose and insulin low
glucagon high

Front 56

High insulin induces an increase in the conc. of a compound that derives from F-6-P in glycolysis. When this compound is present at high conc it leads to activation of glycolysis, and inhibition of gluconeogenesis, what is this compound?

Back 56

F 2,6-BP