Metabolism S4 - Energy Storage Flashcards Preview

ESA1 Callum's cards > Metabolism S4 - Energy Storage > Flashcards

Flashcards in Metabolism S4 - Energy Storage Deck (93):
1

Describe the three major energy stores in the body of a 70kg man.

Include approximate weight and approximate energy content for each store.

Triacylglycerols (TAGs) - 15kg - 600,000kJ

Glycogen - 0.4kg - 4,000kJ

Muscle Protein - 6kg - 100,000kJ

2

How many reactions are involved in glycogen synthesis? (glycogenesis)

4

3

What's the equation of the first reaction in glycogenesis?

Which enzyme catalyses the reaction?

Glucose + ATP ---> G-6-P + ADP

Hexokinase

4

What's the equation for the second reaction in glycogenesis?

What enzyme catalyses this reaction?

G-6-P ---> Glucose-1-Phosphate

Phosphoglucomutase

5

What's the equation for the third reaction in glycogenesis?

Glucose-1-Phosphate + UTP + H2O ---> UDP-Glucose + 2Pi

6

What is the final reaction of glycogenesis?

What two enzymes are involved and what is the difference in their action?

Glycogen (n residues) + UDP-Glucose ---> Glycogen (n+1 residues) + UDP

Glycogen synthase forms 1-4 glycosidic bonds

Branching enzyme forms 1-6 glycosidic bonds

7

how often is a branch produces during glycogen synthesis?

about every 10 subunits

8

Where is glycogen stored and what is it broken down in response to at each respective location?

Liver - In response to fasting

Skeletal muscle - In response to exercise

9

What is the equation for the complete degradation of glycogen?

Glycogen (n residues) + nPi ---> 0.9n G-6-P + 0.1n Glucose

10

Is glycogen ever fully degraded?

No, small sections of primer always preserved

11

How many reactions are involved in the degradation of glycogen?

3

12

Give the equation for the first step of glycogen degradation

What enzymes catalyse this reaction and what varies between their action?

Glycogen (n residues) + Pi ---> Glucose-1-Phosphate + Glycogen (n-1 residues)

Glycogen phosphorylase (1-4 glycosidic cleavage)

De-branching enzyme (1-6 glycosidic cleavage)

13

Give the equation for the second step of glycogen degradation

What enzyme catalyses this reaction?

Glucose-1-Phosphate ---> G-6-P

Phosphoglucomutase

14

How is glucose liberated from glycogen used in the skeletal muscle as compared to the liver?

In skeletal muscle G-6-P produced by step 2 of glycogen breakdown is fed directly into glycolysis for utilisation.

The liver requires another reaction (step 3 of glycogen degradation) to use the liberated glucose

15

Give the equation for step 3 of glycogen degradation

What enzyme catalyses this reaction?

G-6-P + H2O ---> Glucose + Pi

Glucose-6-phosphatase

16

Compare the functions of liver and skeletal muscle glycogen

Liver - Glucose store for all tissues

Muscle - G-6-P store, useful only to muscle cells

17

How do glycogen metabolic disorders arise?

Abnormality in one or more of the enzymes of glycogen metabolism

18

What are the three enzymes that may be defective in a patient with a glycogen metabolism disorder?

Glycogen phosphorylase

Phosphoglucomutase

Glucose-6-phosphatase

19

What 3 effects are seen in glycogen metabolic disorders?

Increased/Decreased amount of glycogen

Glycogen structure may be abnormal

Usually liver or muscle effects

20

What are the clinical consequences of increased or decreased levels of glycogen?

Decreased exercise tolerance

Fasting hypoglycaemia

Tissue damage if excessive storage

21

What is the process of producing glucose from non-carbohydrate sources called?

Gluconeogenesis

22

Why is gluconeogenesis necessary?

To maintain constant glucose level in blood after glycogen been used

Some tissue are glucose dependent (eg. CNS)

23

Where is the main site of gluconeogenesis?

Liver

24

How long do glycogen stores last after eating?

8-10 hours

25

What are the possible substrates for gluconeogenesis?

Pyruvate, Lactate, Glycerol

Essential and non-essential amino acids whose metabolism involves pyruvate or intermediates of the TCA cycle

26

Is Acetyl-CoA a suitable substrate for gluconeogenesis? Explain.

No

Pyruvate dehydrogenase reaction is irreversible

27

What is the overall equation for gluconeogenesis from pyruvate?

2 Pyruvate + 4 ATP + 2 GTP + 2 NADH ---> Glucose + 4 ADP + 2 GDP + 2 NAD+ + 6 Pi + 2H+

28

How are the reversible steps of glycolysis bypassed in gluconeogenesis from pyruvate?

With irreversible reactions

29

How are the irreversible reactions of glycolysis bypassed in gluconeogenesis of pyruvate?

Steps 1 and 3 are bypassed by thermodynamically spontaneous reactions catalysed by phosphatases

Step 10 is bypassed by two reactions driven by ATP/GTP hydrolysis

30

What are the equations for the bypass reactions of steps 1 and 3 in gluconeogenesis?

What enzymes catalyse these reactions?

STEP 1

G-6-P + H20 ---> Glucose + Pi

Glucose-6-phosphatase

 

STEP 2

Fructose-1,6-phosphate + H20 ---> Fructose-6-Phosphate + Pi

Fructose-1,6-biphosphatase

31

What are the two equations for the bypass of step 10 of glycolysis in gluconeogenesis?

What enzymes catalyse these reactions?

1.

Pyruvate + CO2 + ATP + H2O ---> Oxaloacetate + ADP + Pi + 2H+

Pyruvate carboxylase

2.

Oxaloacetate + GTP + 2H+ ---> Phosphoenolpyruvate + GDP + CO2

Phosphoenolpyruvate carboxykinase (PEPCK)

32

How are products of amino acids that are also intermediates of the TCA cycle utilised by gluconeogenesis?

Oxaloacetate is featured in the TCA cycle and in gluconeogenesis, so the intermediates are converted to oxaloacetate so they can be utilised.

33

How is gluconeogenesis regulated and what are the major targets of control?

Hormonal control

PEPCK and Fructose-1,6-biphosphatase

34

How is PEPCK activity controlled?

Increased - Glucagon, Cortisol

Decreased - Insulin

35

How is Fructose-1,6-biphosphatase activity controlled?

Increased - Glucagon

Decreased Insulin

36

In diabetics what is the significance of gluconeogenesis control?

Inadequate levels of insulin allow excess gluconeogenesis to occur which contributes heavily to hyperglycaemia

37

How are TAGs stored and what controls storage?

Note: what promotes and depletes stores?

Anhydrous form in adipocytes

Controlled hormonally

Storage promoted by insulin

Storage depletion activated by glucagon, cortisol, adrenaline, growth hormone and thyroxine

38

How are TAGs produced in the gut delivered to adipose tissue?

In the blood stream transported in chylomicrons

39

Describe the process of Beta-Oxidation of fatty acids.

Hint: What happens to the fatty acids? What's required?

Cycled sequence of reactions oxidises and removes C2 units (acetate) from FAs continuously until only 2 remain

Requires NAD+ and FAD

Cannot occur without oxygen (needed to oxidise NADH and FAD2H formed)

No direct ATP synthesis

All C2 units linked to CoA to form AcetylCoA

40

Where does Lipogenesis occur?

The cytoplasm

41

Give the equation for the formation of a 16 carbon fatty acid

8 AcetylCoA + 7 ATP + 14 NADPH + 6 H+ ---> Fatty acid (C16) + 14 NADP+ + 8CoA + 7 ADP + 7 Pi + 6 H2O

42

How are most steps of lipogenesis catalysed?

Multi enzyme complex known as fatty acid synthase complex

43

Describe how Fatty acids are built up during lipogenesis

Built up from C2 units donated from AcetylCoA

44

Is lipogenesis a reverse of fatty acid degradation? Explain

Nope, units added in the form of MalonylCoA (C3) with subsequent loss of CO2

45

How is malonylCoA produced?

Give an equation and the enzyme that catalyses the reaction

Produced from AcetylCoA

AcetylCoA + CO2 + ATP ---> MalonylCoA + ADP + Pi

AcetlyCoA carboxylase

46

Explain the importance of AcetylCoA carboxylase and explain how it is regulated

Plays important role in controlling rate of lipogenesis

Allosterically controlled (AMP inhibits / citrate activates)

Covalent modification (reversible phosphorylation)

Insulin activates by promoting dephosphorylation

Glucagon and adrenaline inhibit by promoting phosphorylation

47

In what stage of catabolism are amino acids first broken down?

Stage 2

48

Why is amino acid catabolism such a diverse process?

All amino acids have their own unique catabolic pathway

49

What factor is common to all amino acid catabolic pathways?

Initial deamination (-NH2 released and converted to urea)

50

What are some common products of amino acid deamination (C-skeleton products)

Pyruvate

Oxaloacetate

Succinate

Fumarate

Acetyl-CoA

Alpha-ketoglutarate

51

What are ketogenic amino acids?

Amino acids (eg. leucine, lysine) that produce AcetlyCoA when catabolised that can be used in the synthesis of ketone bodies

52

What are glucogenic amino acids?

Amino acids that don't produce AcetylCoA when metabolised and the products are used in gluconeogenesis

53

What amino acids are ketogenic and glucogenic?

isoleucine, threonine, phenylalanine

54

What is transamination?

Transfer of an amino acids NH2 group to a keto acid

55

What is the most common keto acid and what is it converted to during transamination?

alpha-ketoglutarate converted to glutamate

56

What is the enzyme responsible for transamination of alanine?

Give a reaction equation for this process

Hint: The enzyme has two names

Alanine transaminase (ALT)

aka glutamate-pyruvate transaminase

Alanine + alpha-ketoglutarate ----> pyruvate + glutarate

57

What is the enzyme responsible for transamination of Aspartate?

Give a reaction equation for this process

Hint: The enzyme has two names

Aspartate transaminase (AST)

aka glutamate-oxaloacetate transaminase

Aspartate + alpha-ketoglutarate ---> glutamate + oxaloacetate

58

What apart from alpha-ketoglutarate can be used as a keto acid and what is it converted into?

oxaloacetate converted to aspartate

59

What stimulates transaminase synthesis and where are they synthesised?

Cortisol

Liver

60

What is deamination?

Removal of NH2 group from amino acids to form ammonia (which is converted to ammonium)

61

What enzymes are responsible for deamination?

What can be said about their specificity?

L and D amino acid oxidases

Low specificity

62

Why are D amino acid oxidases important and where are they found in high concentration?

Important to convert D-amino acids to keto acids (not optically active)

This is important as D-amino acids (found in plant and bacterial cells) must not be used in protein synthesis as the proteins would be structurally abnormal and non functional

63

What is the enzyme that deaminates glutamine and what is the product of the reaction?

Glutaminase

Glutamate + NH3

64

Give the equation for the breakdown of glutamate into a keto acid.

Give the enzyme that catalyses this reaction

Glutamate + H2O + NAD+ ----> alpha-ketoglutarate + NH4+ + NADH + H+

Glutamate dehydrogenase

65

What is Phenylketonuria?

Inherited disorder resulting in large amounts of phenylketones in the urine

66

What is the metabolic basis for Phenylketonuria?

Phenylalanine is normally oxidised to tyrosine by phenylalanine hydroxylase, In PKU cases this enzyme is defective, causing buildup of phenylalanine.

Phenylalanine is metabolised via other pathways to form phenylpyruvate which is excreted in urine

67

How is Phenylketonuria diagnosed?

Detection of phenylketones in urine or high phenylalanine blood concentration (>0.1mM)

68

How is Phenylketonuria treated and what are the consequences of not treating it?

Treated with diet low in phenylalanine

Left untreated it can inhibit brain development

69

What is the cause of homocystinuria?

Rare autosomal recessive defect in methionine metabolism

70

What is the metabolic basis of homocystinuria?

Cystathionine beta-synthase deficiency

This enzyme normally metabolises homocysteine into cystathionine (which is further converted to cysteine).

Deficiency causes elevated levels of homocyteine and methionine in plasma and homocysteine in the urine

71

What are the physiological effects of Homocystinuria?

Chronic elevated levels of homocyteine cause disorders of connective tissue, muscle, CNS and cardiovasular system

72

Why is homocystinuria easily misdiagnosed in childhood?

Symptoms are similar to Marfan's syndrome's symptoms

73

What is the clinical relevance of measuring creatinine concentration in the blood and urine?

Amount of creatinine excretion in 24hr in the urine is proportional to muscle mass

74

How and when is creatinine produced?

Spontaneous reaction in muscles all the time at constant rate, increases during muscle wasting and high protein diet

75

In what form is ammonia normally present in the body and where does the ammonia come from?

98.5% of ammonia in ammonium ion form

Produced by many tissues and absorbed from the gut

76

What is hyperammonaemia associated with and what tissues are particularly sensitive to it? Explain

Hyperammonaemia seen in liver disease

Associated with blurred vision, tremors, slurred speech coma and eventually death.

Also affects pH in cells of CNS and interferes with neurotransmitter synthesis/release

CNS sensitive to hyperammonaemia due to disruption of TCA cycle which CNS relies on more heavily than other cells

77

Why is ammonia toxic to the body?

Reacts with alpha-ketoglutarate to form glutamate in mitochondria which removes alpha-ketoglutarate from the TCA cycle and disrupts energy supply

78

How is ammonia detoxified?

Conversion to N-compounds such as glutamine or conversion to urea

79

Can ammonia be excreted in urine?

Yup

80

Give an equation for glutamine synthesis from ammonium and the enzyme required

NH4+ + glutamate + ATP ------> Glutamine + ADP + Pi

Glutamine synthetase

81

What happens to glutamine in the liver an kidneys? Why?

Give an equation and any enzymes required

Glutamine ---> Glutamate + NH4+

Glutaminase

Ammonium then excreted in kidneys

Converted to urea in liver

82

Why is urea a good way of disposing of nitrogen?

Non-toxic

metabolically inert

water soluble

high nitrogen content (47%)

83

Where does urea synthesis occur and what is the name of the enzyme pathway responsible?

After urea synthesis, what happens to it?

Synthesis in liver via the urea cycle

Transported to kidneys for excretion

84

Give the full equation for conversion of NH4+ into urea

NH4+ + HCO3- + Aspartate + 3 ATP ---> Urea + Fumarate + 2ADP + AMP + 4Pi

85

How is the Urea cycle regulated?

Enzymes are inducible Induced by high protein diet

Suppressed by low protein/starvation

86

When treating starvation/low protein diet why is it important to reintroduce food gradually?

Starvation has suppressed enzymes of the urea cycle and so lots of protein in the diet all of a sudden will result in hyperammonaemia as ammonia is not metabolised fast enough

87

With inherited disorders of the urea cycle what are the two effects all disorders have?

Hyperammonaemia

Accumulation or excretion of urea cycle intermediates

88

What are the symptoms of defects in the urea cycle and what does their severity depend on?

Depends on severity of defect and how much protein eaten

Vomiting, lethargy, irritability and generally includes mental retardation

Severe cases may include seizures, coma and eventual death.

89

How are defects in the urea cycle managed?

Low protein diet

Replacing essential amino acids in diet with keto acids that use up NH4+ when converted to amino acids

90

How does hyperammonaemia arise as a consequence of liver disease such as cirrhosis?

Livers ability to remove ammonia from portal blood is impaired

91

During excretion of urea from the kidneys how is urea lost from the blood stream if not from filtration in the kidney?

How is this reabsorbed?

Diffuses across the intestinal wall and is broken down by gut bacteria into ammonia to be reabsorbed

92

How does kidney failure affect ammonia concentration in the blood?

Gut bacteria produce ammonia which is absorbed into the blood stream and cannot be metabolised, contributing to hyperammonaemia

93