L2: Protein and Amino Acid Metabolism Flashcards

(61 cards)

1
Q

State some major and minor nitrogen containing compounds.

A

Major: amino acids, proteins, purines & pyrimidines

Minor: creatine phosphate, some hormones (e.g. adrenaline)

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2
Q

How is creatinine formed and at what rate?

A

Breakdown of creatine and creatine phosphate. Formed at a constant rate dependent on muscle mass (unless muscle is wasting)

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3
Q

How does creatinine provide an estimate of muscle mass?

A
  • Filtered by kidneys

- Creatinine urine excretion over 24 hour period is proportional to muscle mass

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4
Q

Alongside being used as an indicator of muscle mass, state another use of creatinine?

A

Indicator of renal function.

High plasma concentration and low urine concentration indicates poor kidney function.

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5
Q

State the reference range for creatinine excreted in urine per 24 hour period for:

  • men
  • women
A

Men: 14-26mg/kg
Women: 11-20mg/kg

Men tend to have larger muscle mass

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6
Q

How is creatinine phosphate used as a small store of energy in muscles?

A

Creatine converted into creatine phosphate by enzyme creatine kinase. Reaction converts ATP -> ADP.

Reaction can be reversed to regenerate ATP.

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7
Q

Define nitrogen balance

A

A measure of nitrogen input - nitrogen output

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8
Q

Define nitrogen equilibrium

A

Intake of nitrogen = output of nitrogen

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9
Q

Define positive nitrogen balance. When is it normal?

A

Intake of nitrogen > output of nitrogen

Increase in total body protein; this is the normal state in times of growth, pregnancy or adult recovering from malnutrition

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10
Q

Define negative nitrogen balance. When is it normal?

A

Intake of nitrogen < output of nitrogen

Net loss of protein. NEVER NORMAL- causes can include trauma, infection or malnutrition

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11
Q

In an average 70kg man, approximately how much nitrogen by mass is in:

  • Body proteins
  • Amino acid pool
  • N-containing compounds
A

Body proteins= 2kg
Amino acid pool= 16g
N-containing compounds= 60g

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12
Q

Where does the body’s nitrogen come from?

A

Dietary protein (16g)

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13
Q

State the four compounds in which nitrogen is excreted

A

Mostly as urea (85%), creatinine, ammonia and uric acid in the urine (some in faeces and sweat)

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14
Q

Define protein turnover

A

Balance between protein synthesis and protein degradation

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15
Q

What two things happens to excess amino acids?

A
  • Converted into intermediates of carbohydrate and lipid metabolism
  • Oxidised to provide energy

THEY ARE NOT STORED

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16
Q

Describe the process of protein turnover

A
  • Amino acids from digested dietary protein and de novo amino acid synthesis enter free amino acid pool
  • Amino acids used to synthesis proteins
  • Amino acids return to free amino acid pool when proteolysis occurs. 75% reutilised for synthesis the rest metabolised in liver
  • Free amino acids metabolised into amino group and carbon skeleton by liver
  • Amino group: nitrogen either incorporated into other compounds or excreted as urea
  • Carbon skeleton -> glucogenic amino acids or ketogenic amino acids
    **Glucogenic amino acids undergo gluconeogenesis
    **Ketogenic amino acids from ketone bodies
    Both produce energy
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17
Q

Amino acids can be glucogenic, ketogenic or both glucogenic and ketogenic; provide one example of each.

A
  • Glucogenic: Glycine
  • Ketogenic: Lysine
  • Both glucogenic & ketogenic: Phenylalanine
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18
Q

When does mobilisation of protein reserves occur?

A

Extreme stress (starvation)

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19
Q

State the effect of insulin and growth hormone on:

  • Protein synthesis
  • Protein degradation
A

Protein synthesis: increase

Protein degradation: decrease

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20
Q

State the effect of glucocorticoids on:

  • Protein synthesis
  • Protein degradation
A

Protein synthesis: decrease

Protein degradation: increase

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21
Q

If, during a starved state, you wanted proteins to be mobilised what hormone would be released?

A

Glucocorticoids (E.g. cortisol)

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22
Q

What can occur, regarding proteins, in Cushing’s syndrome and what are the consequences?

A

Excessive breakdown of protein (due to excess cortisol). This weakens skin structure and leads to striae formation.

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23
Q

State the nine essential amino acids

If learned this huge list may prove truly valuable

A
Isoleucine
Lysine
Threonine
Histidine
Leucine
Methionine 
Phenylalanine
Tryptophan
Valine
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24
Q

State three conditionally essential amino acids and when they may be required from diet

A

Arginine, tyrosine and cysteine when there is a high rate of protein synthesis e.g. pregnancy, growth as child

Arginine can be synthesised by body in small quantities
Tyrosine can be synthesised from phenylalanine
Cysteine can be synthesised from methionine

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25
Define the amino acid pool
Total amount of free amino acids in the body (extracellular and intracellular)
26
The body can synthesise some amino acids (non-essential amino acids); - Where do the carbon atoms for non-essential amino acids come from? - Where does amino group come from?
- Intermediates of glycolysis (C3) - Pentose phosphate pathway (C4 & C5) - Krebs cycle (C4 & C5) Amino group provided by transamination or from ammonia
27
Amino acids are required for synthesis of proteins and also synthesis of other compounds; provide two examples of these other compounds
- Glycine: purines | - Cysteine: glutathione
28
Define transamination
Transfer of an amine group from one amino acid to another (often to a keto acid) using enzymes called aminotransferases
29
Define deamination and where does it occur?
Liberates amino group as free ammonia. Mainly occurs in liver and kidney
30
What do MOST amino transferases do? What is the exception to the rule?
Most amino transferases transfer an amine group to alpha-ketoglutarate to from glutamate. EXCEPTION: aspartate aminotransferase transfers an amine group to oxaloacetate to form aspartate
31
What do all aminotransferases require?
Coenzyme pyridoxal phosphate (vitamin B6 derivative)
32
What aminotransferase enzymes are measured in liver function tests?
- Alanine aminotransferase (ALT) - Aspartate aminotransferase (AST) Levels high in conditions that cause extensive cellular necrosis e.g. viral hepatitis
33
What does alanine aminotransferase (ALT) do?
Converts alanine to glutamate Transfers amino group from alanine to alpha-ketoglutarate to form glutamate
34
What does aspartate aminotransferase (AST) do?
Converts glutamate to aspartate Transfers amino group from glutamate to oxaloacetate to from aspartate
35
What happens to ammonia at physiological pH?
Rapidly converted to ammonium ion
36
Name three enzymes that can deaminate amino acids
- Amino acid oxidases - Glutaminase - Glutamate dehydrogenase
37
What's a keto acid?
Contains ketone group and carboxyl group. (Ketone group in place of amino group and H atom on alpha carbon of amino acid)
38
State two roles of urea
- Remove nitrogen (including toxic ammonia) | - Osmotic role in kidney tubules
39
Where does the urea cycle occur?
In the liver (ornithine to citrulline in mitochondria and rest in cytoplasm)
40
How many enzymes involved in urea cycle?
5
41
Describe how the urea cycle is inducible (but not regulated)?
High protein diet induces/increases enzyme levels. | Low protein diet or starvation represses/decreases enzyme levels
42
Describe what occurs in refeeding syndrome
Occurs when nutritional support given too quickly/too much to severely malnourished patients. The urea cycle has been down regulated due to malnutrition therefore refeeding can cause ammonia toxicity. Re-feed at 5 to 10kcal/kg/day.
43
State some risk factors for refeeding syndrome
- BMI <16 - Unintentional weight loss > 15% in 3-6 months - 10 days or more with little or no nutritional intake
44
What do we generally mean by a defect in urea cycle?
Autosomal recessive genetic disorders caused by deficiency of one of enzymes in urea cycle. Mutations USUALLY lead to partial loss of enzyme function (could lead to total loss). Can lead to ammonia toxicity.
45
Defects in urea cycle often lead to what two things?
- Hyperammonaemia | - Accumulation/excretion of urea cycle intermediates
46
Which child has severe defect in urea cycle and which has a mild defect in urea cycle: A: symptoms day after birth B: symptoms in early childhood
A: severe (may die) B: mild
47
What are two methods of managing symptoms due to defect in urea cycle?
- Low protein diet | - Replace amino acids with keto acids
48
State some symptoms of defects in urea cycle/ammonia toxicity
- Vomiting - Lethargy - Seizures - Mental retardation
49
Explain how ammonia toxicity can cause mental retardation
Ammonia is readily diffusible and toxic to brain. It can: - alter blood brain barrier - pH effects - disruption of cerebral flow - interfere TCA cycle
50
Describe the two ways in which amino acid nitrogen can transported from peripheral tissues to the liver for disposal.
GLUTAMINE: ammonia combines with glutamate to form glutamine which is transported in blood to liver where it is cleaved by glutaminase to reform glutamate and ammonia. ALANINE: amine groups transferred to glutamate. Glutamate then transaminates pyruvate to form alanine which is transported in blood to liver and converted back to pyruvate by transamination. Amino group fed via glutamate into urea cycle for disposal and pyruvate used to synthesise glucose "Glucose-alanine cycle"
51
What's the role of glucose-alanine cycle?
Safely transport amino groups from peripheral tissues to liver via blood.
52
State some diseases the heel prick test identifies.
- Sickle cell - Cystic fibrosis - Congenital hypothyroidism - Inborn errors of metabolism e.g. PKU
53
Describe the aetiology of phenylketonuria (PKU)
Autosomal recessive defect leading to deficiency in phenylalanine hydroxylase. Leads to accumulation of phenyalanine in tissues, plasma and urine. Phenylalanine converted into phenylpyruvate and then into phenylacetate and phenyllactate (phenylketones)
54
What is the presence of phenylketones in urine indicative of?
Phenylketonuria (PKU) High blood phenylalanine would also indicate PKU
55
What does phenylalanine hydroxylase do?
Converts phenylalanine into tyrosine. Tyrosine is important for adrenaline, melanin, thyroid hormones...
56
State some symptoms of phenylketonuria (PKU)?
- Severe intellectual disability - Developmental delay - Seizures - Microcephaly - Hypopigmentation
57
Describe the aetiology of homocystinurias
Autosomal recessive disorder in methionine metabolism
58
Describe the aetiology of homocystinurias
Autosomal recessive disorder in methionine metabolism; most commonly a defect in cystathionine B-synthase (which converts homocysteine into cystathionine)
59
How do you diagnose homocystinurias
- Homocysteine (intermediate in methionine metabolism) excreted in urine - Elevated levels of methionine in plasma - Elevated levels of homocysteine in plasma
60
How do you treat homocystinurias?
- Low methionine diet
61
What factors promote the synthesis of methione from homocysteine
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