Integration Of Metabolism Flashcards by Shannon Keary

What forms of energy production does skeletal muscle rely on?

fatty acid oxidation and carbohydrate oxidation

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During light contraction of skeletal muscle, how is ATP consumption met?

through oxidative phosphorlyation

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During vigorous contraction, how is ATP consumption met?

Muscle stores of glycogen are then broken down to produce ATP

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Under anaerobic conditions, what is pyruvate converted into?

Lactate

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What is the only substrate that the brain can use as a source of energy?

Glucose / carbohydrates

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Which energy source can the brain not use?

The brain cannot metabolise fatty acids

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What can partially substitute for glucose in the brain?

Ketone bodies like 3-Beta-Hydroxy-butyrate

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What can too little glucose in the brain cause?

Hypoglycaemia - faintness and come

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What can too much glucose in the brain cause?

Hyperglycaemia - irreversible damage to multiple organ systems like retinas

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What does the heart utilise for energy substrates?

TCA cycle substrates like free fatty acids and ketone bodies

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What happens to the heart when energy demand > energy supply?

Myocardial infarction

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Name four fuel sources for the heart

Ketone bodies, glucose, fatty acids and lactate

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Why does the heart have alot of mitochondria?

Because the heart is designed for aerobic conditions - high energy supply

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How does the liver store glucose?

As glycogen

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What range does the liver try keep the blood glucose levels between?

4-5.5 mmol/L

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Excess of what can be used to generate glycogen in the liver and muscle?

Excess glucose-6-phosphate

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How are fatty acids stored in adipose tissue?

They are stores as triglycerides in the adipose tissue

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During fasting, wha happens to the Acetyl CoA which is produced?

Much of the Acetyl CoA is used to generate ketone bodies

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What happens to lactate production during periods of intense exercise?

It increases - produced from pyruvate

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What three things can the body initially do when the blood glucose concentration drops below 3mM?

Breakdown liver glycogen stores to maintain levels
Release free fatty acids from adipose tissue
Convert Acetyl CoA into ketone bodies in the liver

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How does the brain get more glucose when the body is in a hypoglycaemic coma?

The skeletal muscle can use ketone bodies and fatty acids, to increase the blood glucose concentration, making more plasma glucose available for the brain which cannot metabolise fatty acids

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After how many hours are the bodies glycogen stores depelated?

12-18 hours

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After the body has depleted its glycogen stores, what is used to generate glucose?

Gluconeogenesis

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How is pyruvate regenerated from lactate?

Using lactate dehydrogenase enzyme

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Which reaction in gluconeogenesis occurs in the mitochondria?

The convertion of pyruvate to oxaloacetate

What enzyme is used to convert pyruvate into oxaloacetate?

Pyruvate carboxylase

How does oxaloacetate move out the mitochondria once it has been produced from pyruvate?

It moves via the malate shuttle, where it is then converted into phosphophenolpyruvate

How do glucogenic amino acids give rise to glucose?

They undergo transamination reactions which results in the production of pyruvate, which yields glucose through gluconeogenesis

where do the reactions of gluconeogenesis occur?

First reaction occurs in mitochondria | Rest in the cytosol

What do ketogenic amino acids give rise to?

Skeletons that can be used to synthesise FAs and ketone bodies.

What happens to pyruvate during anaerobic respiration?

It is taken up by the liver and converted into lactate by LD to replenish NAD+ levels and maintain glycolysis

In the fasting state, what is the main metabolic fuel for the heart?

fatty acids

In the fasting state, what is the main metabolic fuel for the brain?

Glucose

In the fed state, why does insulin stimulate an increase in the number of glucose transporters on the adipocyte surface?

To facilitate glucose uptake to make triglycerides.

Why do plasma levels of ketone bodies increase as the fed state progresses into fasting and then starvation ?

Ketone bodies produced by the liver

The products of which reactions can enter the pathway to increase oxaloacetate production for gluconeogenesis?

Transamination reactions

In the fasting state, glucagon acts to increase the synthesis of glucose from which molecules?

Glycogen, Glycerol and Amino acids.

What generates the bulk of the NADPH needed for anabolic pathways?

Glucose-6-phosphate via the pentose phosphate pathway can also be used as a source for nucleotide production in a pathway that generates the bulk of the NADPH needed for anabolic pathways e.g. cholesterol synthesis.

What are three non-carbohydrate precursoers which enter into the gluconeogenic cycle?

Lactate, Amino acid and glycerol

What is the cori cycle?

The generation of pyruvate from lactate

How does glycerol act as a non-carbohydrtae substrate fo gluconeogenesis?

It is used to produced DHAP

Which are the three reactions of gluconeogenesis which need o be bypassed through using kinase enzymes?

Phosphenolpyruvate to pyruvate Fructose - 1,6 - Bisphosphate to Fructose - 6 - Phosphate Glucose - 6 - Phosphate to Glucose

What enzyme is used to convert Glucose - 6 - Phosphate into Glucose?

Glucose - 6 - Phosphatase

What organs is Glucose - 6 - Phosphatase found in?

Liver and kidneys

What to things are triglycerides broken down into?

fatty acids and glycerol

What are the seven molecules which deamination of all 20 amino acids gives rise to?

``` Pyruvate Oxaloacetate Succinyl CoA Fumerate Acetyl CoA Acetoacetyl CoA Alpha-ketoglutarate ```

What happens to the rest of the amino acid once it has been broken down by deamination?

Remaining compounds are excreted in the urea

which tissues can use ketone bodies as an energy source?

Muscle and brain

What happens to the glucose transporters on the membranes of muscle cells as the muscle contracts?

The number present on the membranes of the muscle cells increases

What three effects does adrenaline have on helping the cell meet the adequate demands for ATP?

Increases the rate of glycolysis in muscle increases th rate of gluconeogenesis in liver Increases the release of fatty acids from adipocytes

what causes an increase in muscle glycolysis, gluconeogenesis and fatty acid breakdown during exercise?

The release of adrenaline

During anaerobic conditions what happens to the glycogen in the muscle?

It is broken down

What is the name of the pathway given to the breakdown of glycogen into glucose?

Glycogenolysis

What triggers glycogenolysis?

Glucagon

How is the Cori cycle used in anaerobic conditions?

Pyruvate is taken up by the liver and converted into lactate, using lactate dehydrogenase - replenished NAD+ levels allows glycolysis to continually occur

What does insulin do?

Stimulates the uptake and use of glucose, and storage of glycogen and fat

What enzymes catalyses the first, irreversible step of glycolysis?

Hexokinase

What are the two different isoforms of hexokinase found in the muscle and the liver?

Hexokinase I is found in the muscle | Hexokinase IV is found in the liver

What is the Michaelis Constant?

The concentration of substrate at which an enzyme functions at half-maximal rate (Vmax)

What is the KM of Hexokinase 1 and what does it mean?

0.1 - this means it is activate at very low concentrations of glucose and therefore is functioning at max velocity at almost all times

Which hexokinase is sensitive to inhibition by product glucose - 6 - phosphate?

Hexokinase 1

What are the four changes which occur during aerobic exercise?

1. Increase in number of glucose transporters in muscle 2. Increase glycolysis in muscle 3. Increase gluconeogenesis in Liver 4. Increased bet oxidation to make Acetyl CoA which is the used to generate ATP

Where does the convertion of lactate into pyruvate occur?

IN the liver

Where does the convertion of lactate into pyruvate occur?

IN the liverDur

During the fasted state, the transamination reactions of amino acid are an important substrate for what process?

Gluconeogenesis

During anaerobic conditions, why is Hexokinase 1 Inhibited?

During anaerobic conditions, glycolysis slows, and the concentration of glucose drops This means that hexokinase is readily active Therefore a lot of glucose is converted into glucoe-6-phosphate Hence glucose - 6 - phosphate accumulates which inhibits hexokinase 1

Where is Hexokinase IV found?

In the liver

what does Hexokinase IV do?

Converts glucose into glucose-6-phosphate in the liver

What is the KM of Hexokinase IV?

What does the KM value of Hexoinase IV indicate?

4 - active at very high concentrations of glucose

Which hexokinase enzyme is more sensitive to G-6-P inhibition?

hexokinase 1

What occurs straight after a meal has been consumed?

- Insulin is secreted, causes glucose to be stored as glycogen - Increase in glycolysis - Acetyl CoA is used to generate fatty acids through Lipogenesis, meaning they can stored for future use

What happens after a period of fasting following a meal?

Glucose has been all stored as glycogen so blood glucose levels start to drop - This triggers glucagon secretion - Glucagon triggers glycogenolysis, and gluconeogenesis - Fatty acid Beta Oxidation occurs so that Acetyl CoA is produced (used as an AP substrate)

What happens after prolonged fasting?

- Glycogen stores have all been used up, so gluconeogenesis dominates - Proteolysis also occurs to make amino acids that can undergo transamination reactions to make pyruvate - used in gluconeogenesis

Why does triglyceride hydrolysis increase during periods of prolonged fasting?

The triglycerides are broken down into glycogen and fatty acids fatty acids used in beta-oxidation to make ATP substrates (Acetyl CoA) Glycogen can assist with gluconeogenesis, enters as DHAP

Why does ketone body synthesis occur during periods of prolonged fasting?

During fasting, gluconeogenesis ic occuring This means all oxaloacetate is being used up Therefore, there may be an excess of Acetyl CoA The excess Acetyl CoA is used to produce Ketone bodies through ketogenesis

How does diabetic ketoacidosis occur?

The body does not produce enough insulin, therefore glucose cannot be stored in cells, body relies on fats for energy fatty acids are broken down into ketone bodies

What happens to the insulin:glucagon ration after periods of prolonged fasting?

Increases further

Which cells of the ISLETs is glucagon released from?

Alpha cells

What two processes does glucagon stimulate in the liver?

Glycogenolysis and gluconeogenesis

What are glucocorticoids?

Steroid hormones which increase synthesis of metabolic enzymes concerned with glucose availability

Wh are ketone bodies produced after periods of prolonged fasting?

Ketone bodies are produced from fatty acids and amino acids in liver to substitute partially the brain’s requirement for glucose