Hypoxia & Tumors Video Flashcards

1
Q

Where is lactic acid produced?

A

Lactic acid is mainly produced in muscle cells and red blood cells

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2
Q

What is the purpose of generating lactic acid?

A

The purpose of generating lactic acid is to replenish NAD+ in the muscles so that glycolysis can run continuously

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3
Q

When is lactic acid formed?

A

L.A is formed when glucose is used for energy at low oxygen

Intense exercise

Infection or disease

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4
Q

What is the final product of glycolysis?

A

Pyruvate is the final product of glycolysis

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5
Q

Which enzyme converts pyruvate to lactate?

A

The enzyme is lactate dehydrogenase converts pyruvate to lactate

Upregulation of lactate dehydrogenation — high amount will trigger this reaction

NAD+ is formed when Lactase dehydrogenase converts pyruvate to lactate

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6
Q

Where does NAD+ go in the Cori Cycle

A

NAD+ stays in the muscle for continuous glycolysis

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7
Q

Where does lactate go?

A

Muscles do not want lactate

Exported to the liver for conversation to glucose

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8
Q

Describe the Cori Cycle

A

Cori cycle is:

Lactate acid being produced in muscles and then exported to the liver for gluconeogenesis

(Lactate will be converted back to pyruvate and follow gluconeogenesis)

Glucose can be re supplied to the muscles

Increase ATP or replenish glycogen stores in muscle

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9
Q

How many ATP for immediate use via glycolysis?

A

We get two ATP for immediate use for every glucose molecule that goes through glycolysis

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10
Q

What is the net balance of ATP in the Cori Cycle?

A

6 ATP molecules is required every time you want to produce glucose via gluconeogenesis in the liver
It’s expensive!

I have produced 2 through glycolysis

So each iteration of the Cori cycle costs 4 ATP — fine on a temporary basis, when ATP needs are immediate

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11
Q

What is the metabolic function of the Cori Cycle?

A

The function of the Cori Cycle is to shift the metabolic burden from the muscles to the liver during intense exercise

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12
Q

Which transcription factor protein is present when there is no oxygen?

A

One major protein known as HIF-1 (hypoxia inducable factor)

It is a transcription factor — helps to make other proteins

It is the statement that there is no oxygen present

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13
Q

Where does HIF-1a go in normal conditions?

A

In normal oxygen conditions HIF-1a stays in the cells.

It is hydroxylated and degraded

Get rid of the HIF if we have oxygen

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14
Q

Where does HIF-1a go in hypoxic conditions?

A

Under hypoxic conditions, HIF-1a is not degraded, instead it goes into the nucleus and forms a complex known as a HIF-1 complex

Bind DNA and initiate a hypoxic response

It’ll upregulate Lactate Dehydrogenase! To make lactate!

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15
Q

Describe what happens to HIF-1a in tumour conditions

A

In a tumor
HIF 1a is in very high levels in tumor environments, it’s not being degraded even in normal oxygen conditions!

If HIF is there, the cell is behaving like there is no oxygen — won’t degrade HIF — we’re running aneorabic respiration!

It’s called the Warburg Effect

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16
Q

What is the impact of the Warburg Effect ?

A

The impact of the Warburg Effect — net loss of 4 ATP per glucose molecule. Cells are only making two ATP

Cells are starved of oxygen. Enough to stay alive but not healthy

High lactate acid = decreases immune response around the tumour. Very low pH around the tumour.

17
Q

What is a target of cancer drug tests?

A

HIF-1a is a cancer drug target