Gluconeogenesis and Lactic Acidosis Flashcards

1
Q

Gluconeogenesis location

A

Mostly liver
Kidney is secondary

9 enzymes in cytosol
1 in mitochondria
1 in ER

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2
Q

Key enzymes of Gluconeogenesis (4)

A

G6Pase
FBPase-1
PEPCK
Pyruvate Carboxylase

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3
Q

Malate and Aspartate

A

Made in mitochondria
Shuttled out into cytosol
Yield OAA

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4
Q

PEPCK

A

2 OAA –> 2 PEP

GTP –> GDP

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5
Q

FBPase-1

A

F 1,6 BP –> F6P

H20 –> Pi

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6
Q

G6Pase

A

G6P –> glucose

H20 –> Pi

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7
Q

Lactate

A

Taken up by liver

Oxidized to pyruvate in cytosol by LDH

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8
Q

ALanine

A

Taken up by liveer

Transaminated by ALT to pyruvate

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9
Q

NADH regeneration

A

Ox of lactate to pyruvate

Ox of malate to OAA

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10
Q

Gluconeogenesis overall

A

2 pyruvate —-> glucose
4 steps irreversible
6 ATP equivalents used
2 NAD+ produced

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11
Q

Glucose transport

A

GLUT2 (hepatocyte)

Gradient favors production

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12
Q

FBPase-1 regulation

A

AMP (-)

F 2,6, BP (-)

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13
Q

Pyruvate Carboxylase regulation

A

Acetyl CoA (+)

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14
Q

Glucagon effect on Gluconeogenesis

A

Inc PKA –> phosphorylation of CREB –> Inc transcription of gluconeogenic enzymes

Inc PKA –> phosphorylation of PFK-2/FBPase-2 –> Dec F2,6 BP

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15
Q

Factors that increase Lactate production

A

Mitochondrial dysfx
Low cellular O2
Cancer Cells
Metformin

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16
Q

Factors the decrease lactate removal

A

Liver dz
In NADH/NAD+ (e.g., EtOH metab)
Defects in gluconeogenesis
Metformin

17
Q

Metformin effects

A

Inc lactate production
Dec lactate clearance

–> Inc Plasma lactate
Okay w/in therapeutic doses because kidney can compensate; only small inc seen.

NOT OKAY w/ DEC Kidney FX

18
Q

Metformin + Tissue Hypoxia

A

Inc lactate production –> Inc plasma lactate

19
Q

Metformin + Liver Dz/Excessive EtOH

A

Dec lactate clearance from hepatocytes –> Inc plasma lactate

20
Q

Where in the cell does G6Pase work?

A

Occurs in ER