Chapter 10 Gluconeogenesis

Front 1

Where does the majority of Gluconeogenesis take place? Where else does Gluconeogenesis take place?

Back 1

90% in liver, 10% in kidney

Front 2

Steps of gluconeogenesis

Back 2

pyruvate  Oxaloacetate (OAA) – Carboxylation by pyruvate carboxylase need coenzyme Biotin and 1 ATP; OAA  malate (need NADH) which then crosses mitochondrial membrane into Cytosol; malate to OAA (produce NADH); OAA to PEP by PEP Carboxykinase; to 2-phosphoglycerate to 3 Phosphoglyceride (use 1 ATP) to glyceraldehyde3P to fructose 1,6 Bisphosphate; to fructose 6 phosphate by fructose 1,6 Bisphosphate; to glucose 6 phosphate to glucose by glucose 6 phosphatase

Front 3

Rate limiting enzyme of Gluconeogenesis

Back 3

1) PEP Carboxykinase
2) pyruvate carboxylase
3) fructose 1,6 Bisphosphate
4) glucose 6 phosphatase

Front 4

Where is Pyruvate Carboxylase found?

Back 4

Liver and kidney mitochondria and found in muscle cells

Front 5

What intermediate molecule that is also involved in the TCA is created during the conversion of Pyruvate to PEP?

Back 5

OAA

Front 6

Which TCA molecule is used solely as a transporter?

Back 6

Malate

Front 7

How is Biotin bound to Pyruvate Carboxylase? (In general, Carboxylase enzymes have Biotin as a cofactor; of course there are a few exceptions).

Back 7

Covalently bound to the enzyme protein by the epsilon amino group of lysine

Front 8

What is Biocytin?

Back 8

covalently bound biotin

Front 9

Acetyl CoA is an Allosteric activator of Pyruvate Carboxylase. Why would an increased amount of Acetyl CoA activate Pyruvate Carboxylase?

Back 9

It is a high energy indicator so if you have a lot of it, its going to cause the reaction to go in the opposite direction and towards Gluconeogenesis

Front 10

Where does Oxaloacetate (OAA) form? Where is it transported to? How is it transported?

Back 10

a. It is formed in the mitochondria and gets transported to the Cytosol
b. It has to convert to malate by mitochondrial malate DH to cross the membrane; once in the Cytosol it gets converted back to OAA by cytosolic malate DH and produces NADH

Front 11

What enzyme converts Fructose 1, 6-BP back to Fructose 6P? What inhibits this enzyme? What activates this enzyme? (Hint: There are various energy metabolites that affect the work of this enzyme and there are also allosteric regulators that affect the work of this enzyme; KNOW BOTH!)

Back 11

a. Fructose 1,6-bisphosphotase does the conversion
b. It is inhibited by high levels of AMP which signals an energy poor state; and high levels of ADP; also inhibited by fructose 2,6-bisphosphate
c. It is activated by high levels of ATP and low levels of AMP

Front 12

Which enzyme helps you bypass the irreversible Hexokinase reaction? Where is this enzyme found? (again: it’s not found everywhere, so be specific)

Back 12

a. Glucose 6-phosphatase and glucose 6-phosphate Translocase which transports enzyme across rER
b. It is only found in the liver and Kidneys

Front 13

Why can the muscle not create glucose via Gluconeogenesis?

Back 13

Muscle lacks glucose 6-phosphatase

Front 14

How much Energy is used up in creating one molecule of glucose?

Back 14

4 ATP, 2 NADH, and 2 GTP

Front 15

What effect does a lack of Fructose 2, 6-Bisphosphate have on the speed of Gluconeogenesis?

Back 15

it'll speed it up, since it inhibits

Front 16

What are the 3 most important sources of Gluconeogenic precursors?

Back 16

a. Glycerol
b. Lactate
c. Pyruvate

Front 17

37. How is Glycerol used to create glucose? (Specifically: Where does it come from? What reactions are performed on it?)

Back 17

Released into the blood by exercising skeletal muscle and by cells that lack mitochondria; Cori cycle- glucose is converted to lactate by exercising muscle which diffuses into the blood. It is then taken up by the liver and reconverted to glucose.

Front 18

How is alpha-Ketoacids used to create glucose? (Specifically: Where does it come from? What reactions are performed on it?)

Back 18

Derived from hydrolysis of tissue proteins; OAA and alpha Ketoglutarate are derived from metabolism of Glucogenic amino acids; these substances can enter the TCA and form OAA, a direct precursor to PEP;

Front 19

What is the Cori cycle? Where does glucose flow through? (Basically draw out the Cori cycle and remember it!)

Back 19

Cori cycle- glucose is converted to lactate by exercising muscle which diffuses into the blood. It is then taken up by the liver and reconverted to glucose and then sent back to the exercising muscles;

Front 20

What are ‘Ketogenic’ compounds? (be general; what molecule would create Ketogenic compounds)

Back 20

Acetyl CoA and compounds that give rise to Acetyl CoA can’t give rise to net synthesis of glucose b/c irreversible nature of pyruvate DH reaction (pyruvate to A CoA), so instead these give rise to ketone bodies

Front 21

How is Gluconeogenesis regulated on a minute-by-minute basis? (Specifically, what molecule is present to regulate this pathway?)

Back 21

Glucagon and availability of gluconeogenic substrates

Front 22

Glucagon performs 2 actions to affect the rate of Gluconeogenesis? One is related to levels of F-2,6BP and the other is related to regulation of activated levels of Pyruvate Kinase. Explain these two phenomenons. How would these regulatory events be affected if there was a sudden elevation of Glucagon in the blood?

Back 22

a. glucagons lower level of F2,6BP which results in activation of F1,6bisphosphatase and inhibition of Phosphofructokinase
b. elevates cAMP levels, which increases Phosphorylation of pyruvate kinase (making it inactive) so higher PEP levels forced to Gluconeogenesis pathway

Front 23

Effect of insulin

Back 23

slows gluconeogenesis

Front 24

What second messenger system is utilized by Glucagon to control the activity of Pyruvate Kinase?

Back 24

cAMP

Front 25

Why is hepatic Pyruvate Carboxylase activated by Acetyl CoA in a starvation state?

Back 25

Need glucose in blood for brain function; fatty acids are metabolized increasing levels of acetyl CoA through beta oxidation of these free fatty acids