Gi--Biochem--Lecture3--Gluconeogenesis

Front 1

How is oxaloacetate formed from pyruvate (enzyme, cofactor, and involved vitamin, and others)

Back 1

1) pyruvate moves into mitochondria from cytoplasm
2) pyruvate is converted into oxaloacetate
3) enzyme: pyruvate carboxylase
4) cofactor: biotin
5) vitamin B7
6) CO2 required

Front 2

What regulates the conversion of pyruvate to oxaloacetate?

Back 2

build up of acetyl coA levels stimulates this reaction

Front 3

What are the reactions involved in the conversion of pyruvate to phosphoenolpyruvate, and what is required?

Back 3

MITOCHONDRIA:
1) pyruvate-->oxaloacetate, pyruvate carboxylase, requires CO2
2) oxaloacetate-->malate, mitochondrial malate dehydrogenase, NADH oxidized
3) malate moves into cytosol
CYTOSOL
4) malate-->oxaloacetate via cytosolic malate dehydrogenase regenerating NADH
5) oxaloaceetate-->PEP, enzyme: PEP carboxykinase releases CO2, GTP formed

Front 4

How are the carbons from aspartate and glutamate transferred from mitochondria to cytosol?

Back 4

aspartate forms oxaloacetate-->malate
other amino acids form malate via TCA cycle

Front 5

Does CO2 become incorporated into glucose, what happens?

Back 5

No, the CO2 that is incorporated inthe pyruvate carboxylase step in the formation of OAA gets released when PEP is made

Front 6

What precursors would need the malate shuttle and why? What DOES NOT need the malate shuttle?

Back 6

Malate is the major carrier of the carbons in amino acids such as alanine, glycine and serine which form pyruvate and other amino acids. It is needed to transfer reducing equivalents from the mitochondria to the cytosol to be used in the production of oxaloacetate from the malate. LACTATE does not need the malate shuttle

Front 7

How does the aspartate alphaketoglutarte shuttle operate?

Back 7

MITOCHONDRIA:
1) the amine on glutamate transfered to oxaloacetate such that oxaloacetate forms aspartate and glutamate forms a-ketoglut
2)aspartate and alpha ketoglut transferred out to cytosol
3) aspartate transaminated to form oxaloacetate and glutamate regen from alpha-ketoglut

Front 8

Under what conditions would does the aspartate alphaketoglut shuttle function? Why? elaborate on how this leads to glucose formation

Back 8

During excercise, lactate builds up which converts to pyruvate in cytosol. This conversion already generates reducing equivalents and therefore malate cycle is not needed. The pyruvate then goes into mitochondria and gets converted to OAA which must be sent back into cytosol for PEP formation

Front 9

Describe the PEP shuttle and enzyme

Back 9

Oxaloacetate gets converted to PEP within the mitochondria via the mitochondrial PEP carboxykinase enzyme and PEP is then shuttled out into the cytosol

Front 10

How is PEP converted to G-6-P

Back 10

PEP converts to glyceraldehyde 3-P via several reversible reactions. Glyceraldehyde 3-P combines with dihydoxyacetone to form Fructose 1,6 bisP then goes to Fructose 6-P the Glucose 6-P

Front 11

What are three points in gluconeogenesis that are regulated

Back 11

Pyruvate to PEP
-Pyruvate carboxylase (pyruvate->OAA)
-PEP carboxykinase (OAA to PEP)
-Pyruvate kinase (PEP-->pyruvate)

Fructose 1,6 bisP-->Fructose 6 P

Glucose-6-P-->Glucose

Front 12

What is the committed step in the synthesis of glucose via TCA cycle?

Back 12

conversion of OAA to PEP

Front 13

How is the committed step regulated?

Back 13

-this conversion only happens in liver
-regulated by transcription
1) increased transcrip in starvation
2) increased by glucocorticoids and TH
3) insulin inhibits

Front 14

What happens to pyruvate kinase during gluconeogenesis? why?

Back 14

It is important that pyruvate kinase is turned off so that the PEP being formed does not get converted back to pyruvate