4. Amino Acid and Protein Metabolism (Part II) Flashcards
1
Q
What did the DRI report determine in terms of sex and age?
A
Separate requirements could not be determined for women versus men, or for older adults and the elderly
2
Q
What did the DRI report determine in terms of pregnant and lactating women?
A
- “Essentially there is no data”
- In terms of ethical issues, it is not normally recommended to perform low-protein diet studies on pregnant women and children
- The new tracer methods allow these studies to be achieved over a shorter period of time, which means that new data is incoming
3
Q
What did the DRI report determine in terms of children?
A
- “Data is based on factorial analysis”
- Largely theoretical, and resembles determining a budget
4
Q
What did the DRI report determine in terms of infants?
A
- “Data is based on intake of breast milk”
- AI is known, but not the EAR and RDA
5
Q
How do the nutritional needs of unhealthy infants differ from healthy, breastfed infants?
A
The needs are more known for unhealthy infants, since their presence within the hospital allows for an opportunity for their analysis
6
Q
What did the DRI report determine in terms of physical activity?
A
- “In view of a lack of compelling evidence to the contrary, no additional dietary protein is suggested for healthy adults undertaking resistance or endurance exercise”
- However, the data has changed DRASTICALLY since this report
7
Q
What complicates nutrition research in women?
A
- Women possess two major stages of the menstrual cycle (follicular and luteal)
- Researchers must always ask themselves: “does the hormonal profile affect metabolism?”
8
Q
A study by the Sick Kids was conducted concerning lysine requirement in men and women, during the follicular and luteal stages. What were the results?
A
- Women in the follicular phase (before ovulation) had a lower protein requirement, but it wasn’t significantly different
- If terms of lean body mass, lysine requirement increased significantly following ovulation (luteal phase)
9
Q
What studies concerning amino acid requirements do we need?
A
- Age groups
- Females
- Physiological conditions
- Functional criteria of adequacy
- Conditionally indispensable amino acids and special products
10
Q
What studies concerning amino acid requirements in specific physiological conditions do we need? Which is the most important?
A
- Healthy infants (most important)
- Prematurity
- Intravenous feeding
- Inborn errors
- Metabolic stress
- Liver disease
- Exercise
11
Q
What did the North American Protein Advisory Board analyze in Montreal in 2013? What was the consensus?
A
- Whether amino acid and protein requirement in critical illness were higher than in the healthy state
- Designed randomized control trials
- Protein requirement in general is much higher for individuals in critical conditions
12
Q
What do IV regimens bypass?
A
- Bypass the GI tract (splanchnic control)
- Infuse nutrients directly into circulation
13
Q
What was the lipid portion of IV regimens based on in the past? What was the effect? What is now currently available?
A
- An emulsion of soybean oil, which contains a large portion of linoleic acid (omega-6), producing pro-inflammatory cytokines
- Opposite desired effect in a critical illness
- Products using oleic acids are now available
14
Q
What are limitations of intravenous regimens?
A
- Metabolic uncertainty
- Amino acids must be free, soluble, and stable
15
Q
Which amino acids may not be used in IV treatments? Why?
A
- Tyrosine is insoluble
- Cysteine is unstable since it oxidizes, and is not soluble
16
Q
How may tyrosine insolubility in IV treatments be tackled? Which age group may not receive this treatment, and why?
A
- Increasing phenylalanine, since tyrosine is derived from phenylalanine
- Does not function in babies, as they do not metabolize tyrosine efficiently, which causes large accumulations of phenylalanine or tyrosine
17
Q
What was the traditional approach to IV feeding and tackling tyrosine insolubility in babies?
A
- Ignoring the problem, and letting the body take care of it
- Increasing phenylalanine may not be used in babies
18
Q
What are two soluble tyrosine precursors?
A
- N-acetyltyrosine
- Glyclyl-tyrosine (we possess many dipeptidases that can hydrolyze the peptide bond)
19
Q
What does Vamin originate from? What does Vaminolactin originate from?
A
- Vamin: egg-patterned
- Vaminolactin: human milk-patterned
20
Q
What does Vamin contain? What is the resulting nitrogen retention?
A
- High phenylalanine and low tyrosine
- Nitrogen retention is 80%
21
Q
What does Vaminolactin contain? What is the resulting nitrogen retention?
A
- Low phenylalanine and low tyrosine
- Nitrogen retention of 70%
22
Q
What resulted from the addition of phenylalanine to Vaminolactin? What does that indicate?
A
- Increased nitrogen balance
- Indicates that aromatic amino acids are limiting in Vaminolactin
- However, as increased phenylalanine may not be provided in babies, another solution was necessary
23
Q
What resulted from the addition of N-acetyltyrosine to Vaminolactin?
A
Did not increase nitrogen balance, and thus did not accomplish the required function
24
Q
What resulted from the addition of glycyl-tyrosine to Vaminolactin?
A
- Increase in nitrogen balance, and functioned extremely well
- However, the solution was extremely expensive, and the patient population that utilizes this approach is limited to babies
25
What is an example of an inborn error of metabolism?
Phenylketonuria (PKU)
26
Under normal circumstances, what percentage of dietary proteins is composed of phenylalanine and tyrosine?
- 4% phenylalanine
- 4% tyrosine
- Slightly less than average
27
How is tyrosine produced?
By hydroxylation of phenylalanine by phenylalanine hydroxylase
28
What is phenylketonuria caused by?
- Inborn error of metabolism
| - Phenylalanine hydroxylase is non-functional, caused by a genetic polymorphism (autosomal recessive)
29
What are the consequences of PKU?
- Phenylalanine builds up as it cannot be converted to tyrosine
- Phenylalanine ends up being catabolized to phenylketones that are excreted in large amounts in urine
- The accumulation of phenylalanine and/or phenylketones are toxic to the developing brain and may cause seizures and severe developmental delays
30
How is phenylketonuria diagnosed? When is it screened for?
- Blood tests or urinalysis
| - Analyzed in neonatal screening programs
31
Which types of diseases are screened for in neonatal screening programs?
The diseases must be relatively commonly occurring, and must possess an effective treatment that, if instituted early, makes a difference in the outcome of the disorder
32
What is the treatment for PKU?
- Immediate treatment is IMPERATIVE
| - Low phenylalanine (ex: Phenyl-Free) and high tyrosine diet
33
When is treatment for PKU imperative? When is it less important?
- When the brain is still developing, maintaining the low-phenylalanine diet is extremely important
- In adulthood, the brain is less vulnerable to increased phenylalanine and phenylketones
- The treatment is also imperative for pregnant women, as their phenylalanine can affect the fetal brain by crossing the placenta
34
What is protein deficiency normally accompanied by?
- Energy deficiency (ex: anorexia nervosa)
| - Vitamin and mineral deficiencies
35
Which organ is most affected by protein deficiency, as shown by Dr. Wykes piglet study? Why?
- The gut
- High protein turnover
- 75% of the proteins in the gut are remade every day in the control
36
Which organ is least affected by protein deficiency, as shown by Dr. Wykes piglet study? Why?
- Muscle
- Low protein turnover
- Piglets only remake 8% of proteins in muscle tissue every day (humans only remake 2%)
37
Why must the gut maintain a rapid rate of turnover?
As the epithelial cells lining the intestine must remain intact to allow for proper transport and absorption of nutrients
38
In terms of clinical observations, what occurs if an individual is malnourished?
The gut atrophies, gets thinner as there is less metabolic tissue present, and slows down
39
What did Voigt originally propose in terms of protein requirement?
- He proposed a requirement of 0.9-1.0 g/kg/d
- His date was ignored by the DRI requirement report based on nitrogen balance (0.66 g/kg/d)
- However, the situation is currently being re-examined, and the requirement ressembles more of what he originally concluded
40
What method is used to find the point of minimal variability between the line of the slope at low intakes and the line of the slope at constant intakes (breakpoint) in nitrogen balance studies?
Bootstrapping
41
Using the same nitrogen balance data from 50 years ago, using modern statistical methods, what corresponds to the breakpoint (EAR)? What is the RDA?
- EAR: 0.9 g/kg/d
| - RDA: 1.0 g/kg/d
42
What is the AMDR for protein?
10 to 35%
43
What recommendations (new or old) does the AMDR correspond to?
- The NEW recommendations
| - They also correspond to the current protein intake in North America, assuming food security is maintained
44
What decreases when an individual is fed 0.6 g/kg/d for 7 days?
- Protein turnover
| - Albumin synthesis (negative acute phase protein)
45
What are the functions of albumin?
- Functions to maintain proper fluid balance
| - Possesses many binding sites to transport nutrients and certain toxins
46
What increases when an individual is fed 0.6 g/kg/d for 7 days?
Fibrinogen synthesis (positive acute phase protein)
47
What are positive acute phase proteins? Give an example.
- Increase during a fever, infection, stress or wound-healing
- Ex: fibrinogen, antibodies, immune cells
48
What decreases when an individual is fed 0.75 g/kg/d for 7 days?
- Protein turnover
- Albumin synthesis (negative acute phase protein)
- Glutathione synthesis
49
What are negative acute phase proteins?
- Decrease during a fever, infection, stress or wound-healing
- Ex: albumin
50
What susceptibility increases in the absence of glutathione?
Susceptibility to oxidative stress
51
What eases the determination of adequate protein levels in infants?
The fact that they are growing
52
What is the ideal birth weight? How does it change in 5 months?
- Ideal birth rate: 7.5 pounds
| - 5 months: doubles to 15 pounds
53
What does a child falling off the growth curve indicate?
- Growth issue
| - Dietary issue or failure to thrive
54
What does a child crossing lines upwards the growth curve indicate?
Obesity
55
Why are inadequacies in the diet observed rapidly in piglets?
Because piglets double their birth weight in a week, while babies require 5 months
56
What do parietal cells release? What is their function?
- Release HCl
| - Function at acidic pH to break proteins into smaller peptides
57
What occurs to proteins in the liver during the fed state?
- High rate of protein synthesis
| - Catabolism of amino acids that may be present in excess
58
How does insulin affect proteins and amino acids during the fed state?
- Promotes amino acid transport into cells
| - Promotes protein synthesis in many tissues
59
How does glucagon affect proteins and amino acids during the fasted state?
- Promotes protein breakdown
| - Helps the amino acid pool maintain homeostasis, as there is no input from the diet
60
How does the fasted state affect nitrogen balance? How?
- Nitrogen balance is negative
| - Increase in protein breakdown, amino acid catabolism, and urinary nitrogen
61
What percentage of body weight does the liver and muscle make up?
- Liver: 3%
| - Muscle: 40%
62
What percentage of the BMR is the liver and muscle responsible for?
- Liver: 21%
| - Muscle: 21%
63
What percentage of the body's protein synthesis is the liver and muscle responsible for?
- Liver: 30%
| - Muscle: 30%
64
What percentage of proteins that are newly synthesized every day is the liver and muscle responsible for?
- Liver: 50%
- Muscle: 3%
- Liver is much more metabolically active
65
What are the four anabolic functions of the liver?
- Constitutive protein synthesis (remain in the liver and are not secreted into plasma)
- Plasma protein synthesis
- Gluconeogenesis
- Lipogenesis
66
What are the two catabolic functions of the liver?
- Amino acid catabolism
| - Urea cycle
67
What occurs during hypertrophy of muscle tissue?
- Growth
- Anabolism (insulin)
- Activation of the PI3K-Akt pathway
68
What occurs during atrophy of muscle tissue?
- Wasting
- Catabolism (glucagon)
- Activation of the ubiquintin-proteosome pathway
69
What do insulin clamp studies involve?
Providing an infusion of insulin at a constant rate
70
What occurs when the hyperinsulinemic state occurs without glucose infusion?
Fatal state
71
What does the hyperinsulinemic state promote? What are the consequences?
- Promotes amino acid transport into cells and decrease protein breakdown
- Results in a drastic decrease in plasma amino acids
72
What is infused in insulin clamp studies? Why?
- Insulin infusion: hyperinsulinemic state
- Glucose infusion: to maintain euglycemia (5 mM/L) or hyperglycemia (10 mM/L)
- Amino acid infusion: to maintain euAAemia or hyperAAemia
73
How many enzymes are required to synthesize the nine essential amino acids?
- 59 enzymes
| - Expensive and complicated
74
How many enzymes are required to synthesize the eleven non-essential amino acids?
- 17 enzymes
- Easy to synthesize as they arise from a common precursor (glucose)
- They are used for more than protein synthesis (i.e. special products)
75
Explain the quantity of enzymes that are needed to synthesize essential and non-essential amino acids in terms of a survival point of view.
- Essential amino acids: survival advantage to be able to rely on diet, and give up the synthetic capacity
- Non-essential amino acids: survival advantage to maintain the capacity to synthesize, as they are so important in metabolism
76
Which special products may arise from a precursor pool of amino acids, and may be followed through a tracer?
- Plasma proteins
- Glutathione
- Enzymes
77
What percentage of proteins synthesized in the body are a part of our visceral tissues? What are they?
- 50%
- Gut, liver, lungs, pancreas
- Vital-function organs
78
What percentage of proteins synthesized in the body are a part of our muscles?
30%
79
What percentage of proteins synthesized in the body make up plasma proteins and RBCs?
20% (together)
80
Which component of protein synthesis may fluctuate enormously (from 10 to 25%) to allow for a healthy immune response?
Positive acute-phase proteins increase in response to infection or inflammation
81
What creates a compromised immune response if an individual is undernourished?
Protein metabolism is slowed down, and they will have a decreased capacity to synthesize positive acute-phase proteins
82
What is the function of mucins? What are they?
- Special amino acid product
| - Protect the lining of the gut from acids and toxins
83
Which indispensable amino acids compose the tripeptide glutathione?
Glycine, glutamate, and cysteine
84
Which amino acids are in high-demand as precursors for special products?
Glycine, glutamate, and cysteine
85
In general, do dispensable amino acids have a high or low flux of amino acids through the body?
High
86
Synthesis of dispensable amino acids accounts for what percentage of the BMR?
8%
87
Describe the intestinal-renal axis for the synthesis of arginine.
- Intestine: glutamate and proline are synthesized into citrulline, which is released to the kidney
- Kidney: citrulline is converted to arginine
88
What functioning organs are required for the synthesis of arginine?
Intestine and kidney
89
What are the three critical special functions of arginine?
1) Necessary for the functioning of the urea cycle to detoxify ammonia
2) Precursor for polyamines
3) Important in nitric oxide synthesis
90
What are polyamines?
Very potent anabolic regulators that are important in growth
91
What is the first observed effect when arginine is withdrawn in the diet? What are the consequences?
- Rising ammonia level
| - Toxic to the brain, and may cause a particular type of tremor, vomiting, convulsions, and then death
92
May hyperammonemia from arginine withdrawal be treated?
- Yes, by providing IV arginine
- Stops the complications extremely rapidly because arginine allows the proper functioning of the urea cycle to detoxify ammonia
- May ALSO be treated by providing citrulline
93
Which age group requires arginine? Which age group doesn't?
- Arginine is essential in babies
| - Arginine is non-essential in adults
94
What does a textbook suggest in terms of serine synthesis?
Serine is synthesized from a three-carbon intermediate of glycolysis in the liver
95
What was Dr. Wykes hypothesis concerning serine synthesis?
- That serine does not arise from the glycolysis pool, but from the gluconeogenesis pool
- The Cori cycle was used as a rational
96
What experiment allowed to uncover the origins of serine synthesis?
- A label was introduced within a glucose molecule to follow its appearance in serine
- Look at proteins that are synthesized in the liver, and secreted in the plasma
97
What would happen to the label within the glucose molecule if "textbook" serine synthesis was right?
- In glycolysis, the glucose molecule is cut in half to produce two three-carbon intermediates
- If "textbook" serine synthesis was right, then serine would be produced with all three carbon atoms labeled
98
What would happen to the label within the glucose molecule if gluconeogenesis serine synthesis was right?
The serine produced would be a heterogeneous mixture of three-carbons, two-carbons, and one-carbon labels
99
Which synthesized liver protein that's secreted into plasma was used to analyze the origins of serine synthesis?
- Apolipoprotein B-100 is found in VLDL
- VLDL is purified into Apo-B, which is hydrolyzed into its individual amino acids
- Focus on the serine and measure how many carbons are in the label
100
Which intermediates were observed to determine the origins of serine synthesis?
- Glucose
- Pyruvate
- Lactate
- Alanine
- Serine
101
Which intermediates were triply-labelled? What does that indicate based on their origin?
- Pyruvate, lactate, alanine
- Arise from peripheral tissue glycolysis, in which the end-products are transported back to the liver through the Cori or Cahill cycle
102
Which intermediates possessed very few triply-labelled molecules? What does that indicate based on their origin?
- Glucose and serine
- Glycolysis produces three-carbon intermediates, enters the TCA cycle of hepatocytes, and subsequently undergoes gluconeogenesis in the liver, producing a mixture of labels
103
Are glycolysis and gluconeogenesis a mirror image of each other?
No
104
What does methionine produce by the cleavage of a methyl group?
Homocysteine
105
What does homocysteine produce through the addition of a serine?
Cystathionine
106
How does cystathionine form cysteine?
Breaks off the part that used to be methionine, which leaves serine and a single sulfur atom, forming cysteine
107
What special products may cysteine form?
Taurine
108
What is the function of taurine? Where is it contained in large amounts?
- Involved in retinal development
| - Possessed in high concentration in muscle
109
How are sulfur amino acids classically viewed as? How should they be viewed instead?
- Classically viewed as a pathway
| - But, they should be viewed kinetically as a cycle
110
What is the key regulatory point in the kinetic view of sulfur amino acids?
Methionine activated to homocysteine
111
What are the two metabolic options of homocysteine?
- Re-methylated to methionine
| - Transsulferated to cysteine
112
Why are homocysteine concentrations kept low?
Since they are a very potent oxidant, which may damage arteries
113
What mechanism for homocysteine is increased if cysteine concentrations are low?
Transsulfuration to cysteine increases
114
What mechanism for homocysteine is increased if cysteine concentrations are high?
Re-methylation to methionine increases
115
The DRIs of which sulfur amino acids are typically viewed as a whole?
Methionine and cysteine
116
Which nutrients are involved in the metabolism of sulfur amino acids?
- FAD (riboflavin - vitamin B2)
- NAD (niacin - vitamin B3)
- Pyridoxine (vitamin B6)
- Folate (vitamin B9)
- Cobalamin (vitamin B12)
- Choline
117
Which nutrient requirement is tied to protein intake? Why?
- Vitamin B6 (pyridoxine)
| - As it is involved in amino acid metabolism rather than energy metabolism
118
Which reactions may be necessary for the synthesis of special products?
Methylation reactions
119
Sulfur amino acid metabolism requires the functioning of which organ?
The liver
120
Which sulfur amino acids are premature infants less able to synthesize? Why?
- Cysteine because there is a bottleneck in the transsulfuration pathway
- Cysteine is a conditionally essential amino acid in newborns
121
What explains the insolubility of cysteine, disrupting intravenous feeding?
Cysteine is oxidized to cystine, which is not soluble
122
What deficiency may occur from a decreased availability of cysteine?
Taurine deficiency
123
Describe the unusual peptide bond contained in glutathione.
- Gamma
- Peptide bond occurs between the carboxylic acid (gamma-carbon) on the R group of glutamate
- This unusual peptide bond is not hydrolyzed in the same way
124
Where is glutathione present: plasma or intracellularly?
- Hardly any glutathione in plasma
| - 1000 times higher concentration intracellularly
125
What are the two ways glutathione protects against oxidative stress in cells?
1) Conjugates reactive-oxygen species, making them more stable
2) Conjugates with electrophiles (e.g. toxins or drugs), decreasing their toxicity
126
How does Tylenol (acetaminophen) poisoning occur? What is the treatment?
- When the drug is not conjugated rapidly enough with glutathione, which is potentially fatal
- The treatment is an analog of glutathione
127
Which individuals should not be taking acetaminophen? Why?
- Individuals who consume an extremely high-quantity of alcohol
- Since they tend to have lower levels of glutathione, particularly in their liver
128
Is glutathione essential?
Yes, it is essential for survival
129
How is the utilization of glutathione in inflammatory states?
- Utilization of glutathione is very high
- If the synthesis cannot be increased to compensate for the increased consumption, it increases the vulnerability to potential drug toxicity or oxidative stress
- Adequate protein intake is necessary to form glutathione
130
Would it be logical to intake a glutathione supplement?
- No, since this is an expensive and illogical way to intake glutamate, cysteine, and glycine
- Also, every cell must synthesize its OWN glutathione, as it cannot cross cell membranes
131
Describe creatine synthesis.
1) Kidney: glycine and arginine combine to form an intermediate
2) Liver: methyl group is transferred from methionine to produce creatine
132
Where is the largest pool of creatine found? What is its function?
- In muscle
- ATP is utilized to place a high-energy phosphate bond on creatine to produce phosphocreatine
- Phosphocreatine is a source of high-energy phosphate bonds when ATP charge gets low
133
What is urinary creatinine an indicator for?
Muscle mass
134
What may urinary creatinine samples over 24 hours be used as an indicator for?
Kidney function
135
How does creatine affect osmoregulation?
Increases total body water
136
What is creatine useful for?
- Power athletes (rather than endurance athletes)
| - Certain neuromuscular disorders
137
Differentiate creatine, phosphocreatine, and creatinine.
- Creatine: special amino acid product
- Phosphocreatine: phosphorylated creatine (source of high-energy phosphate bonds)
- Creatinine: phosphocreatine is metabolized to creatinine for excretion in urine
138
What affects the partitioning of homocysteine apart from the cysteine supply?
- Pyridoxine (vitamin B6)
- Folate (vitamin B9)
- Cobalamin (vitamin B12)
