Integration of metabolism Flashcards

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1
Q

What does the brain use for energy source in its metabolism

A

The brain mainly uses glucose to provide energy for ATP that is needed for neuronal processes

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2
Q

What substitutes can it use if this is not abundantly present

A

When glucose is not available in high concentrations, it can partly switch to metabolising ketone bodies. It cannot metabolise fatty acids.

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3
Q

What happens to brain in hypoglaecemia and hyperglycaemia

A

In hypoglycaemia neuronal transmission is inhibited and this can lead to faintness and coma. In hyperglycaemia fluid build up and impaired blood barrier separation can lead to irreversible nerve damage to brain caused by cranial oedema and disrupted concentrations in fluid

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4
Q

What energy supply does skeletal muscle use in vigorous exercise

A

Skeletal muscle uses glucose in vigorous exercise in anaerobic respiration which is released from glycogen stores

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5
Q

What is the limiting factor of skeletal muscle in vigorous exercise

A

The oxygen supply, which is not sufficient for oxidative phosphorylation to supply ATP needed for muscle contraction

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6
Q

How is cardiac muscle tissue adapted for constant beating of heart

A

Cardiac muscle tissue can metabolise many energy containing substances, uses only aerobic respiration and is very rich in mitochondria

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7
Q

What energy supply does cardiac muscle cells use

A

Cardiac muscle cells can use many different molecules for aerobic phosphorylation, glucose, lactate, ketone bodies, fatty acids

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8
Q

What metabolic roles (carbohydrates and lipids) does the liver have

A

Liver can store and produce glucose, is therefore critical in blood glucose concentration, and is involved in lipoprotein transport needed for transport of cholesterol and triglycerides

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9
Q

What substance is used in pentose phosphate pathway and what does it produce

A

In pentose phosphate pathway glucose-6-phosphate is used to produce nucleotides and NADPH that is needed in cholesterol synthesis

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10
Q

What can pyruvate and other TCA cycle intermediates be source for

A

Pyruvate and other TCA intermediates can be used for the production of non-essential amino acids. Pyruvate can also be used for ketone body, cholesterol and lipid synthesis in form of acetyl-coA. The amino acids can then also be used to produce nucleotides.

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11
Q

What three things happen in the body on short term to prevent hypoglycaemia

A

Glycogen storages can be converted to glucose and released from liver, free fatty acids will be released by adipose tissue and liver will produce ketone bodies from acetyl-coA

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12
Q

Why does muscle tissue use free fatty acids and ketone bodies in hypoglycaemia

A

Muscle tissue will use free fatty acids and ketone bodies for respiration in fasting to make more glucose available for brain and nervous tissue

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13
Q

How long does glycogen storage work for

A

Glycogen storage in the body will last for about 12 to 18 hours

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14
Q

What non-carbohydrate precursors can be used for gluconeogenesis

A

Some amino acids, lactate and glycerol can be used for gluconeogenesis

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15
Q

What is the Cori cycle and where does it take place

A

Lactate that is produced in anaerobic respiration can be taken up by liver cells and reconverted into pyruvate by lactate dehydrogenase and then used to produce glucose. This glucose will then be released and can be used for respiration again.

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16
Q

In what form can glycerol be used for gluconeogenesis

A

Glycerol can be converted to dihydroxyacetone phosphate (DHAP) which can be used for gluconeogenesis when it is converted to glyceraldehyde 3-phosphate (G3P)

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17
Q

Which extra enzymes are required for gluconeogenesis and where are they located

A

Pyruvate carboxylase that converts pyruvate to oxaloacetate is found in mitochondria, phosphoenolpyruvate carboxykinase that converts oxaloacetate to phosphoenolpyruvate in cytoplasm, fructose-1,6-biphosphatase that converts fructose-1,6-biphosphate to fructosephosphate in cytoplasm, glucose-6-phosphatase that converts glucose-6-phosphate to glucose

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18
Q

How many ATP is required per glucose for gluconeogenesis

A

Per glucose produced in gluconeogenesis 6 net ATP is lost

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19
Q

What seven molecules are formed after deamination of all amino acids

A

Pyruvate, acetyl coA, acetoacetyl coA, oxaloacetate, a-ketoglutarate, succinyl coA and fumerate

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20
Q

What are the two types (metabolically) of amino acids and their products

A

Metabolically there are glucogenic and ketogenic amino acids, which can respectively be used to give rise to glucose and to ketone bodies

21
Q

Why can fatty acids and ketogenic amino acids not be used for gluconeogenesis

A

Fatty acids and ketogenic amino acid can only be converted to acetyl coA in TCA cycle and because two CO2 is lost per cycle there is no net production of glucose because the same amount of carbon is added and lost

22
Q

What is ATP used for in muscle cells (3 processes)

A

For contraction by actin and myosin, for maintaining and restoring calcium sarcoplasmic concentrations and maintaining and restoring electrochemical gradient by Na/K-pump

23
Q

How does muscle cell adapt glucose supply to demand

A

In exercise muscle cells upregulate glucose transporters in their membranes

24
Q

What is the effect of adrenalin on muscle cells, liver and adipocytes

A

Adrenalin increases the rate of glycolysis in muscle cells, increases gluconeogenesis in the liver and stimulates release of fatty acids by adipocytes

25
Q

How does muscle cell compensate for glucose supply in vigorous contraction

A

In vigorous exercise when the ATP demand cannot be supplied by aerobic contraction, glycogen in muscle cells in broken down into glucose and after glycolysis pyruvate is converted to lactate to replenish NAD+

26
Q

How much percent of body mass is made up of skeletal muscle, brain and nerves, adipose tissue, liver and heart

A

40% of body mass is made of skeletal muscle, 2% of brain and nerves, 15% of adipose tissue, 1% of heart and 2% of liver

27
Q

What is the normal blood glucose concentration and which organs maintain this

A

4 mM in the blood, this is maintained by the liver that can take up or release glucose

28
Q

What happens to acetyl-CoA after a meal

A

Acetyl-coA is produced in glycolysis from glucose taken up by the liver to serve as building block for production of fatty acids, which can later be used by muscle cells and other cells in aerobic respiration

29
Q

Which enzymes in glycolysis catalyse essentially irreversible reactions

A

Hexokinase which converts glucose to glucose-6-phosphate, phosphofructokinase that converts fructose-6-phosphate to fructose-1,6-biphosphate and pyruvate kinase that converts phosphoenol pyruvate to pyruvate

30
Q

Which reaction in gluconeogenesis occurs in the mitochondria and which in the cytoplasm

A

The reaction from pyruvate to oxaloacetate by pyruvate carboxylase takes place in mitochondria, the rest of the reactions from oxaloacetate to glucose takes place in the cytoplasm

31
Q

What happens to acetyl-coA in fasting

A

In fasting, the acetyl-coA produced mainly from breakdown of fatty acids in beta-oxidation is used to produce ketone bodies

32
Q

How can enzyme activity be controlled in metabolic pathway (2 ways)

A

Enzyme activity is usually controlled at early steps in a metabolic pathway and can occur through product inhibition of the reaction of control by hormones

33
Q

How is blood glucose concentration controlled by liver and muscle

A

Under the influence of insulin and glucagon, liver and muscle cells take up glucose and convert it to glucose-6-phosphate by hexokinase. Liver cells can also release glucose by means of converting it back by glucose-6-phosphatase.

34
Q

What is the Michaelis constant

A

The concentration at which an enzyme converts substrate at half the maximum reaction velocity

35
Q

How is hexokinase I inhibited in muscle cell under anaerobic conditions

A

When muscle cell experiences anaerobic conditions, the TCA cycle stops and this leads to a slow down of glycolysis as well, which results in an accumulation of glucose-6-phosphate, the product of hexokinase, which leads to inhibition of hexokinase I by product inhibition

36
Q

How does hexokinase IV differ from hexokinase I and where is it found

A

Hexokinase IV is much less sensitive to glucose (substrate) concentrations and therefore has higher Km and is also not affected by product accumulation of glucose-6-phosphate like hexokinase I

37
Q

Where is glucose-6-phosphatase found and what is its product

A

Glucose-6-phosphatase is found in liver cells and it coverts glucose-6-phosphate into glucose

38
Q

What are glucocorticoids and what is their function

A

Glucocorticicoids are steroid hormones that stimulate the synthesis of metabolic enzymes involved in gluconeogenesis or glycogenolysis and lipolysis

39
Q

What are the effects of insulin on hepatocytes, myocytes, adipocytes

A

Insulin promotes the upregulation of glucose transporter proteins to the membrane in hepatocytes, myocytes and adipocytes and hence uptake of glucose, it promotes glycogen synthesis in hepatocytes and myocytes, it promotes glycolysis for fatty acid production in hepatocytes, it promotes glucose and fatty acid uptake and triglyceride synthesis in adipocytes

40
Q

What are the effects of glucagon on hepatocytes, myocytes, adipocytes

A

Glucagon promotes glycogenolysis and gluconeogenesis in hepatocytes, it promotes beta-oxidation in myocytes to preserve glucose for brain. It also promotes lipolysis in adipocytes and fatty acid release in hepatocytes and adipocytes

41
Q

How does effect adrenaline differ from glucagon

A

Adrenalin differs from glucagon in that it promotes both glycogenolysis in the liver and in skeletal muscles, where glucagon only promotes glycogenolysis in the liver

42
Q

What happens to glucagon/insulin ratio in prolonged fasting

A

In prolonged fasting, glucagon is produced in much higher quantities than insulin and the ratio increases

43
Q

How are TCA cycle intermediates, proteins and fatty acids used in prolonged fasting

A

TCA cycle intermediates are reduced to facilitate gluconeogenesis, proteins are broken down and amino acids are used for gluconeogenesis and ketone body synthesis, fatty acids are released from adipose tissues and broken down to produce ketone bodies to supply energy demand of brain

44
Q

What do adipose cells do in prolonged fasting

A

Adipose cells under the influence of glucagon hydrolyse triglycerides and release fatty acids to supply fatty acids for oxidation in skeletal muscle and other tissue and to provide substrate for ketone body production

45
Q

What is difference between type 1 and type 2 diabetes mellitus

A

In diabetes type 1, there is not enough insulin produced due to destruction of β-cells in the pancreatic islets. In diabetes type 2, the body has become insensitive to insulin although it is still produced in normal quantities

46
Q

What are the complications of diabetes mellitus to the body

A

Because of the insulin disfunction, the body is in a constant state of starvation which leads to high ketone body concentrations that can lead to fatal ketoacidosis, high free fatty acids in blood which can lead to plaques and atherosclerosis. It can also lead to hypoglycaemia which leads to fainting or coma or hyperglycaemia which can also lead to brain and nerve damage.

47
Q

How can diabetes lead to cardiovascular complications

A

High glucagon can lead to high concentrations of free fatty acids that can lead to atherosclerosis and hence cardiovascular complications

48
Q

How can diabetes lead to acidosis

A

In state of starvation in diabetes, there will be much ketone bodies produced as an energy source which are acidic and can lower the blood pH and lead to acidosis

49
Q

How does insulin deficiency lead to increased hepatic output of glucose and thus hyperglycaemia

A

Insulin deficiency can lead to increased glucagon secretion which promotes gluconeogenesis in the liver which increases the blood glucose concentration but cannot adequately be taken up by the body and thus leads to hyperglycaemia