Protein and Amino Acid Metabolism Flashcards Preview

Z OLD ESA 1- Metabolism > Protein and Amino Acid Metabolism > Flashcards

Flashcards in Protein and Amino Acid Metabolism Deck (172):
1

Give 8 nitrogen containing compounds in the body?

Amino acids, Proteins, Purines, Pyrimidines, Porphyrins (haem), Creatine, Neurotransmitters (e.g. dopamines, Some hormones (e.g. adrenaline)

2

What is creatinine?

Breakdown product of creatine and creatine phosphate

3

What can creatinine be used as?

A useful clinical marker

4

Where is creatinine produced?

In muscle

5

What can creatine phosphate be used as?

A very short term energy supply of ATP in skeletal muscle

6

At what rate is creatinine usually produced?

Constant rate depending on muscle mass

7

How is creatinine excreted?

Filtered via kidneys into urine

8

What is creatinine excretion over a 24 hour period proportional to?

Muscle mass

9

What is the result of creatinine excretion over 24hrs being proportional to muscle mass?

It can provide an estimate for muscle mass

10

What is creatinine commonly used as an indicator for?

Renal function

11

What do raised creatinine levels indicate regarding kidney function?

Damaged nephrons

12

Why can’t we use a urine volume to determine nephron damage?

Because would vary depending on urine dilution

13

When is the body said to be in N equilibrium?

When intake = output

14

What is happening to body protein in N equilibrium?

No change in total body protein

15

When is N equilibrium normal?

In adults

16

What is happening in positive N balance?

Intake > output

17

What happens to body protein in positive N balance?

Increase in total body protein

18

When is positive N balance the normal state?

In pregnancy, growth or an adult recovering from malnutrition

19

What is negative N balance?

When intake

20

What happens to body protein in negative N balance?

Net loss of body protein

21

When is negative N balance normal?

Never

22

Give 3 causes of negative N balance

#NAME?

23

Describe the nitrogen balance in a 70kg male

- 16g N in from dietary nitrogen
- 16g N in amino acid pool 
- 2g N lost in skin, hair and nails 
- 14g N lost in N-waste products

24

Where does the N in the amino acid pool go?

N-containing compounds, and cycled round to and from body protein

25

How much is there of N-containing compounds in the body of a 70kg male?

60g

26

How much of body protein is there in the body of a 70kg male?

2kg

27

What are the N-waste products?

#NAME?

28

What is given when dietary protein is digested?

Free amino acids

29

Other than dietary protein digestion, how can free amino acids be produced?

By de novo amino acid synthesis

30

What are free amino acids in cycle with?

Cellular proteins in muscle

31

What happens in the cycle between free amino acids and cellular proteins in muscle?

Free amino acids are made into cellular proteins in synthesis, and cellular proteins are made into free amino acids in proteolysis

32

What happens to free amino acids in emergency situations?

They are split into their carbon skeleton and amino group in the liver

33

What happens to the amino group produced when free amino acids are split in emergency situations?

It is converted into urea, and excreted in urine

34

What happens to the carbon skeleton produced when free amino acids are split in emergency situations?

- Glucogenic amino acids undergo gluconeogenesis 
- Ketogenic amino acids are converted to ketone bodies

35

What is a glucogenic amino acid?

One that can be converted to glucose by gluconeogenesis

36

Give 2 glucogenic amino acids

#NAME?

37

What is a ketogenic amino acid?

One that can be converted into ketone bodies

38

Give 2 ketogenic amino acids

#NAME?

39

Give 2 amino acids that are both glucogenic and ketogenic

#NAME?

40

What does wether an amino acid is glucogenic or ketogenic depend on?

The side chain

41

What can protein be mobilised to produce?

Glucose

42

Why is protein mobilised to produce glucose?

To meet the need for glucose of some tissues

43

When does mobilisation of protein reserves occur?

During extreme stress, including starvation

44

How is mobilisation of protein reserves controlled?

Hormones

45

Which hormones control the mobilisation of protein reserves?

- Insulin
- Growth hormone 
- Glucocorticoids (e.g. cortisol)

46

What is the effect of insulin and growth hormone on protein?

#NAME?

47

What effect do glucocorticoids have on protein?

- Decrease protein synthesis 
- Increase protein degradation

48

When can excessive breakdown of protein occur?

Cushing’s syndrome

49

What is Cushing’s syndrome caused by?

Excess cortisol

50

What is the result of the excessive breakdown of protein in Cushing’s syndrome?

It weakens the skin structure, leading to striae formation

51

How many different types of R groups are there in amino acids?

20

52

What does an amino acids R group determine?

What type of amino acid it is

53

How do amino acids link together?

Through the formation of peptide bonds

54

How can amino acids be obtained other than dietary intake?

The body can synthesise some amino acids that it requires

55

Where do the carbon atoms for non-essential amino acids come from?

- Intermediates of glycolysis (C3) 
- Pentose phosphate pathway (C4 & C5)
- Krebs cycle (C4 & C5)

56

Where does the amino group for non-essential amino acids come from?

#NAME?

57

What are amino acids required for?

Synthesis of other important compounds

58

Give 3 things tyrosine is important for the synthesis of

- Catecholamines 
- Melanin
- Thyroid hormones

59

What is histidine important for the synthesis of?

Histamine

60

What is arginine important in the synthesis of?

Nitric oxide

61

What is nitric oxide important for?

Vasaldilation

62

Give 2 things cysteine is important for the synthesis of?

- Hydrogen sulphide 
- Glutathione

63

What is hydrogen sulphide important for?

Signalling

64

What is serine important in the synthesis of?

Sphingosine

65

Give 3 things tryptophan is important in the synthesis of?

#NAME?

66

Give 4 things glycine is important in the synthesis of

- Purines 
- Glutathione 
- Haem 
- Creatine

67

Why is the ability to remove nitrogen from amino acids essential?

To allow the carbon skeleton of amino acids to be utilised in oxidative metabolism

68

What can happen to nitrogen from amino acids once removed?

It can be incorporated into other components or excreted from the body as urea

69

What are the two main pathways that facilitate the removal of nitrogen from amino acids?

#NAME?

70

What enzyme is required for transamination?

Aminotransferase

71

What does aminotransferase do?

Transfers the amino group from amino acid to the keto acid α-ketoglutarate

72

What is the result of the action of aminotransferase?

The amino acid is converted to a keto acid, and the keto acid α-ketoglutarate is converted to glutamate

73

What is the alternative to using the keto acid α-ketogluatarate for transamination?

Using the keto acid oxaloacetate

74

What enzyme is required when using the keto acid oxaloacetate for transamination?

Aspartate aminotransferase

75

What does aspartate aminotransferase do?

Converts the amino acid to a keto acid, and oxaloacetate to aspartate

76

What do all amino transferases require?

The coenzyme pyridoxal phosphate

77

What is pyridoxal phosphate a derivative of?

Vitamin B

78

What are the key aminotransferase enzymes?

- Alanine aminotransferase (ALT) 
- Aspartate aminotransferase (AST)

79

What amino acid conversion does alanine aminotransferase catalyse?

Alanine to glutamate

80

What amino acid conversion does aspartate aminotransferase catalyse?

Glutamate to aspartate

81

What is routinely measured as part of a liver function test?

Plasma ALT and AST levels

82

What do the results of the plasma ALT and AST levels mean?

Aren’t normally present in plasma, so if found, bad

83

Where will plasma ALT and AST increase?

In conditions causing extensive cellular necrosis

84

Give 3 conditions that may cause extreme cellular necrosis

- Viral hepatitis 
- Autoimmune liver disease
- Toxic injury

85

What does deamination do?

Liberates amin group as free ammonia

86

Where does deamination mainly occur?

In the liver and kidney

87

What is deamination important for?

- Utilisation of keto acids for energy 
- Deamination of dietary D-amino acids

88

Where are dietary D-amino acids found?

#NAME?

89

What is the problem with ammonia?

It’s very toxic

90

What must be done to ammonia in the body?

Must be removed

91

How is ammonia removed?

#NAME?

92

What happens to ammonia at physiological pH?

It is rapidly converted to ammonium ion

93

Give 3 enzymes that can deaminate amino acids

- Amino acid oxidases
- Glutaminase 
- Glutamate dehydrogenase

94

Does urea have a high or low nitrogen content?

High

95

Is urea toxic?

No

96

Is urea hydrophilic or hydrophobic?

Very hydrophilic

97

What is the advantage of urea being very hydrophilic?

It is very water soluble, so can easily excrete in urine

98

Is urea chemically reactive or inert?

Inert

99

How can urea be broken down?

By bacteria

100

What is released when bacteria break down urea?

NH 3

101

How is most urea excreted?

In urine via kidneys

102

What important role does urea perform in kidney tubules?

Osmotic role

103

Where does the urea cycle occur?

In the liver

104

How many enzymes does the urea cycle involve?

5

105

What is the amount of urea normally related to?

Need to dispose of urea

106

Is amount of urea under direct control?

No, just governed by amount of substrate

107

What induces high urea cycle enzyme levels?

A high protein diet

108

What represses urea cycle protein levels?

- Low protein diet 
- Starvation

109

Is the urea cycle regulated?

No, but can be induced

110

When can re-feeding syndrome occur?

When nutritional support is given to severely malnourished patients

111

What causes re-feeding syndrome?

Ammonia toxicity

112

Why does ammonia toxicity occur when re-feeding malnourished patients?

Because the urea cycle has been down regulated, so the body can’t cope with the amount of ammonia being produced

113

How is re-feeding syndrome prevented?

By re-feeding at 5 to 10 kcal per kg per day, raising gradually to full needs within a week

114

What are the risk factors for re-feeding syndrome?

- BMI 15% in 3-6 months 
- ~17 days with little/no nutritional intake

115

What causes defects in the urea cycle?

Autosomal recessive genetic disorders

116

What defects occur in the urea cycle?

Deficiency in one of the enzymes in the urea cycle

117

How often to defects in the urea cycle occur?

~1 in 30,000 live births

118

What do mutations in enzymes involved in the urea cycle cause?

Partial loss of enzyme function

119

Why are defects in the urea cycle only partial losses of enzyme function?

Complete loss would be incompatible with life, and the foetus would die

120

What do defects in the urea cycle lead to?

- Hyperammonemia 
- Accumulation/excretion of urea cycle intermediates

121

What is hyperammonemia?

Too much ammonia in the blood

122

What does the severity of defects in the urea cycle depend on?

- Nature of defect 
- Amount of protein eaten

123

How quickly do severe urea cycle disorders show symptoms?

Within 1 day of birth

124

What happens if severe urea cycle defects are left untreated?

The patient will die

125

What can be the case with mild urea cycle deficiencies?

Symptoms don’t show until early childhood

126

What are the symptoms of urea cycle deficiencies

- Vomiting 
- Lethargy
- Irritability
- Mental retardation
- Seizures
- Coma

127

How are urea cycle disorders managed?

- Low protein diet 
- Replace amino acids in diet with keto acids

128

What is the biochemical basic of ammonia toxicity?

It is readily diffusible, so can easily access through the blood brain barrier, and is highly toxic to the brain

129

At what levels must blood levels of ammonia be kept?

Very low- 25-50µmol/L

130

What are the potential effects of too much ammonia?

- Interfere with amino acid transport and protein synthesis
- Disruption of cerebral blood flow
- Alkalisation of blood 
- Interfere with metabolism of excitatory amino acid neurotransmitters 
- Alteration of blood-brain barrier 
- Interfere with TCA cycle

131

Why can excess ammonia interfere with the TCA cycle?

It can react with α-ketoglutarate to form glutamate

132

What are the two mechanisms for the safe transport of ammonia from tissues for disposal?

- Glutamine 
- Alanine

133

How does the glutamine mechanism of safe ammonia transport work?

- Ammonia combined with glutamate to form glutamine 
- Glutamine transported in blood to liver or kidneys, where it is cleaved by glutaminase to reform glutamate and ammonia 
- In the liver, ammonia is fed into the urea cycle. 
- In the kidney, ammonia is excreted directly into urine

134

How does the alanine mechanism of safe ammonia transport work?

- Alanine formed in peripheral tissues by transamination of pyruvate- essentially, pyruvate is combined with ammonia to form alanine 
- Alanine is transported in blood to the liver
- In the liver, it is converted back to pyruvate by transamination 
- Amino group is fed via glutamate into urea cycle for disposal as urea, and pyruvate is used to synthesise glucose

135

How many inherited diseases involving defects in amino acid metabolism are there?

Over 50

136

What causes defects in amino acid metabolism?

Either total, or more commonly partial, loss of enzyme activity

137

What can happen is problems in amino acid metabolism are left untreated?

They frequently lead to intellectual impairment

138

What does treatment of defects in amino acid metabolism involve?

Restricting specific amino acids in the diet

139

What is the heel prick test?

A test that every child in western countries receives to systematically screen for diseases

140

What diseases are tested for with the heel prick test?

- Sickle cell disease
- Cystic fibrosis 
- Congenital hyperthyroidism
- Inborn errors in metabolism

141

What inborn errors in metabolism are tested for using the heel prick test?

- Phenylketonuria 
- Maple syrup urine disease
- Isovaleric acidaemia 
- Glutaric aciduria 
- Homocystinuria

142

Why are the diseases in the heel prick test tested for?

Because something, often dietary modification, can be done about them, but if not done as soon as possible, can lead to the development of things such as mental retardation

143

What is the most common inborn error of amino acid metabolism?

Phenylketonuria (PKU)

144

What causes PKU?

Deficiency in phenylalanine hydroxylase

145

What is the inheritance pattern of PKU?

Autosomal recessive

146

Where is the affected gene in PKU?

Chromosome 12

147

What is the result of the lack of phenylalanine hydroxylase?

Accumulation of phenylalanine in tissue, plasma and urine

148

How can PKU be detected?

Phenyl ketones in urine and musty smell

149

What is the treatment for PKU?

#NAME?

150

What high protein foods should be avoided in PKU

- Meat
- Milk 
- Eggs

151

What are the symptoms of PKU?

- Severe intellectual disability 
- Developmental delay 
- Microcephaly (small head)
- Seizures
- Hypo-pigmentation

152

How can the symptoms of PKU be avoided?

Early intervention

153

What causes the symptoms of PKU?

Not producing enough tyrosine

154

Why is not enough tyrosine produced in PKU?

No phenylalanine hydroxylase, so phenylalanine not converted to tyrosine

155

What pathways are affected by lack of tyrosine?

#NAME?

156

What builds up in the blood in PKU?

Phenylalanine

157

Where does the phenylalanine come from?

Dietary protein and endogenous protein

158

What does the build up of phenylalanine in the blood lead to?

Accumulation of phenylketones

159

Why does build up of phenylalanine in the blood lead to accumulation of phenylketones?

Because phenylalanine is converted to phenylpyruvate by transamination, which is then converted into phenylacetate and phenyllactate

160

What causes homocystinurias?

Problems breaking down methionine

161

What is the result of problems breaking down methionine?

Excess homocystine excreted in urine

162

What is homocystine?

2 homocysteines linked together by a disulphide bond- the oxidised fomr of homocysteine

163

What is the inheritance pattern of homocystinurias?

Autosomal recessive

164

What defect causes homocystinurias?

In cystathionine

165

What cystathionine defect is most common?

ß-synthase

166

What do homocystinurias affect?

#NAME?

167

What is the treatment for homocystinurias?

- Low methionine diet
- Avoid meat, milk, fish, cheese, nuts and eggs
- Cysteine, Vit B 6 , betaine, B 12 , and folate supplements

168

What accumulates in homocystinurias?

Methionine and homocysteine

169

Why does methionine and homocysteine accumulate in homocystinurias?

No cystathionine ß-synthase, so homocysteine not converted to cystathionine. Because homocysteine not removed, methionine also accumulates because they interconvert into each other

170

What is the result of the lack of conversion into cystathionine in homocystinurias?

There is a consequent lack of cysteine, which comes from cystathionine

171

What is the homocysteine to methionine conversion promoted by?

- Betaine
- B 12
- Folate

172

What is elevated plasma homocysteine shown to be associated with?

Increased risk of cardiovascular disease