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Medical Biochemistry > Topic 8: Gluconeogenesis, Cori & Alanine Cycle > Flashcards

Topic 8: Gluconeogenesis, Cori & Alanine Cycle Flashcards

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USMLE® Step 1 flashcards
1
Q

What is the most important source for Carbon in gluconeogenesis?

A

BLOOD LACTATE

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2
Q

What is the main gluconeogenic organ/tissue?

A

LIVER!

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3
Q

What is the second most important source of C for gluconeogenesis?

A

Amino Acids:
Most can contribute to glucose –> glucogenic
Some can only to ketones –> ketogenic

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4
Q

What are the ketogenic only amino acids?

A

Leucine and Lysine

Can go into Acteyl-CoA and then Ketones

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5
Q

How much gluconeogenesis is from Fatty Acids?

A

Barely any, only the Glycerol Backbone can be used and 3 C remainder from ODD chain FA’s for proprionate.

Fatty acid chains will be used for fuel rather than gluconeogenesis considering they are utilized generally in times of fasting/starvation

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6
Q

What enzyme removes FA’s from the Glycerol backbone?

A

Lipase

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7
Q

What do fatty acids get used to make?

A

Acetyl CoA for:

ATP (TCA Cycle) or Ketones

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8
Q

What do even chain fatty acids make?

A

Carbons are cleaved 2 at a time –> copious Acetyl CoA

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9
Q

What do odd chain fatty acids make?

A

Mostly Acteyl CoA until 3 C’s are left –> Proprionate!

Proprionate can be anapleurotic in the TCA Cycle to make Succinyl CoA. This can lead to glucose formation.

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10
Q

What is proprionate used for in ruminants?

A

Main gluconeogenic substrate.

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11
Q

What are the 4 enzymes that are used to overcome glycolysis so that gluconeogenesis can take place?

A

1) Pyruvate Carboxylase and 2) PEP Carboxykinase both to overpower Pyruvate Kinase.
3) Fructose-1,6-Bisphosphatase to get past PFK
4) Glucose-6-Phosphatase to get past Hexokinase

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12
Q

What is the function of Pyruvate Carboxylase?

A

Pyruvate –> OAA in the matrix

ATP is used, CO2 is incorporated to make OAA
Requires Biotin/B7

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13
Q

What is the function of PEP Carboxykinase?

A

OAA –> PEP in the cytosol

GTP is used and CO2 is generated.

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14
Q

What is Step 1 of gluconeogenesis?

A

Pyruvate is converted via Pyruvate Carboxylase to OAA.

ATP is used and CO2 is used. Requires B7/Biotin.

OAA via the Malate-Aspartate Shuttle is moved to the cytosol. (NADH used in matrix, NADH made in cytosol)

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15
Q

What is Step 2 of gluconeogenesis?

A

OAA via PEP Carboxykinase is converted to PEP.

GTP is used and CO2 is generated

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16
Q

What is Step 3 of gluconeogenesis?

A

PEP via Enolase makes 2-Phosphoglycerate.

17
Q

What is Step 4 of gluconeogenesis?

A

2-Phosphoglycerate via Phosphoglyceromutase moves the phosphate to make 3-Phosphoglycerate.

18
Q

What is Step 5 of gluconeogenesis?

A

3-Phosphoglycerate via Phosphoglycerate kinase makes 1,3-bisphosphoglycerate.

ATP is used.

19
Q

What is Step 6 of gluconeogenesis?

A

1,3-BPG via Glyceraldehyde-3-Phosphate Dehydrogenase makes Glyceraldehyde-3-Phosphate.

NADH is used, free Phosphate is yielded

20
Q

What is Step 7 of gluconeogenesis?

A

GA-3-P (or DHAP since Aldolase does convert between the two and F-1,6-BP) via Aldolase is converted to Fructose-1,6-Bisphosphate

21
Q

What is Step 8 of gluconeogenesis?

A

F-1,6-BP via Fructose-1,6-bisphosphatase to Fructose-6-phosphate.

H20 is used and free Pi (phosphate) is generated.

22
Q

What is Step 9 of gluconeogenesis?

A

Fructose-6-Phosphate via Glucosephosphate isomerase is converted to Glucose-6-Phosphate.

23
Q

What is Step 10 of gluconeogenesis?

A

Glucose-6-Phosphate via Glucose-6-Phosphatase is turned into the final product: GLUCOSE!! YAY, we did it!

Used H2O and yields a free Phosphate (Pi)

24
Q

How is gluconeogenesis regulated by insulin and glucagon?

A

Insulin –> inhibition
Glucagon –> activation

the 4 special enzymes are up-regulated:
1) Pyruvate Carboxylase 2) PEP CarboxyKinase 3) Fructose-1,6-Bisphosphatase 4) Glucose-6-Phosphatase

25
Q

What else stimulates gluconeogenesis?

A

Catecholamines (Epi and NorE)
AND
Glucocorticoids (cortisol)

26
Q

What cells can perform Gluconeogenesis?

A

Mitochondria containing cells

Pyruvate carboxylase is in the mitochondrial matrix

27
Q

What tissues perform gluconeogenesis the most?

A

LIVER of course
Kidney somewhat
Small Intestine a bit

Only tissues capable of releasing glucose to the blood.

28
Q

Does the brain make glucose?

A

NO NO NO NO – (that means no! not nitric oxide)

29
Q

How does skeletal muscle indirectly contribute to gluconeogenesis?

A

Lactic Acid Cycle (Cori Cycle)
AND
Glucose-Alanine Cycle

30
Q

How does the Lactic Acid Cycle/Cori Cycle Work?

A

Lactic Acid is released from skeletal muscle in times of anaerobic metabolism. Liver takes up Lactate and Oxidizes it to form pyruvate –> TCA Cycle+ETC or Gluconeogenesis.

Glucose released is picked up, turned into pyruvate –> cycle continues

31
Q

How does the Glucose-Alanine Cycle work?

A

When muscle has no glucose/glycogen and needs energy, AA’s are burned in muscle.
Amino group is transaminated to Pyruvate to make Alanine.
Alanine is released, liver picks up, deaminates to make pyruvate –> TCA Cycle+ETC or Gluconeogenesis.
Glucose released is picked up, turned into pyruvate –> cycle continues.

32
Q

What is Cushing’s Syndrome?

A

Hyperadrenocorticism

33
Q

What does hyperadrenocorticism do?

A

Excess Gluconeogenesis –> AAs begin to contribute –> skeletal muscle degrades, heart muscle degrades, collagen in tendons degrade –> why we see weak skin, hair, pendulous abdomen, and fat buildup (hyperglycemia)

Literally converting muscle to fat. Hyperglycemia brings on PU/PD from osmotic imbalance as well.

34
Q

What does lactic acidosis do?

A

Comes from over production or under utilization of lactic acid. Happens when > 5 mM (normal is 1.2mM)

Decreased blood pH (acidosis) and HCO3

35
Q

What causes lactic acidosis?

A

Disrupted TCA Cycle or ETC
Liver Disease (can’t utilize Lactate)
Ethanol (competition for NAD+)
Various drugs - phenformin

36
Q

Why does ethanol compete for NAD+?

A

Ethanol metabolism takes precedence in the liver uses up NAD+. Cannot perform gluconeogenesis in presence of alcohol/ethanol since it requires NAD+ for Malate-Aspartate Shuttle and Lactate to Pyruvate.

37
Q

Why do we care about alcohol poisoning in veterinary medicine?

A

4-Methylpyrazole (Fomepizole) used to inhibit Alcohol Dehydrogenase (enzyme that metabolizes ethanol) for:
Methanol (wood alcohol) –> Formaldehyde
Ethylene glycol (antifreeze) –> Oxalic acid –> precipitates with Ca++ in the kidney –> rapid renal failure

38
Q

Why is ingesting alcohol after exercise a bad idea?

A

You’ve already used up your glycogen stores and built up Lactic Acid. NAD+ is used up by alcohol –> blocking gluconeogenesis = bad idea!

39
Q

What vitamin is crucial for gluconeogenic enzymes to function properly? Which enzymes require it?

A

Vitamin B7/Biotin

Pyruvate Carboxylase (Step 1)
Propionyl-CoA Carboxylase (Ruminant gluconeogenesis to make Succinyl-CoA from Proprionate)

Medical Biochemistry (26 decks)

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