Dietary Proteins 1 Flashcards
1
Q
T/F amino acids are stored by the body?
A
false
-not stored by the body
2
Q
What is the amino acid pool?
A
- free amino acids inside the body
- about 90-100g
3
Q
What are the input sources to the amino acid pool? (5)
A
- amino acid from dietary protein (particularly essential amino acids, 100g/day), have to get essential AA from dietary, body cannot synthesize them
- amino acid from degradation of body protein (400g/day)
- non essential amino acids synthesized from simple intermediates of metabolism
4
Q
output pathways of amino acid pool? (5)
A
- synthesis of body protein (400g/day)
- synthesis of essential N containing compounds such as creatine, neurotransmitters (30g/day)
- energy generation sources such as glucose and ketone bodies (overnight fasting) and fatty acids (fed state)
5
Q
How much protein does a 70kg person have?
A
12kg
6
Q
Which organ has most protein?
A
muscle
7
Q
How big is our amino acid pool?
A
100g
8
Q
How many amino acids are used for protein synthesis?
A
20
9
Q
How many amino acids can be synthesized by our body?
A
11
10
Q
What is nitrogen balance?
A
- determined by the difference between amount of protein intake (N) and protein excreted (urine, sweat, feces)
- protein balance
- net rate of protein synthesis
11
Q
What is zero nitrogen balance?
A
N intake = N excretion
- healthy adult
- nitrogen equilibrium
- amino acid pool steady
12
Q
Positive nitrogen balance?
A
N intake > N excretion
- growth, pregnancy, body builder, recovery from trauma
- have increased requirement of dietary protein to achieve nitrogen balance
13
Q
Negative nitrogen balance?
A
N intake < N excretion
- reduced dietary protein intake, or incomplete protein, or illness (chronic infection, cancer, burns, surgery) without adequate intake
- impaired bodily function under prolonged negative nitrogen balance
- essential amino acid deficiency , mainly used for synthesis
14
Q
Dietary protein requirements?
A
- animal protein have high biologic value (contains all essential amino acids)
- animal protein is easily digested
- vegetable protein has low biologic value (need to eat various vegetables) - essential amino acids, cannot be synthesized in body
15
Q
What are the essential amino acids?
A
phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, leucine, lysine, arginine (children)
16
Q
Vegetable combinations to eat for essential amino acids? (7)
A
pic
17
Q
How much protein does a sedentary lifestyle person need to eat?
A
- RDA is 0.8g/kg/day protein
- intended to replace losses and prevent nutrient deficiency
18
Q
How much protein does a person with an active lifestyle need to eat?
A
- active life 1.2-1.7 g/kg/day
- endurance athlete 1.2-1.6
- body builder 1.2
- power sports 1.4-1.7
- intended to replace muscle breakdown with synthesis
- timing: high quality protein within 1 hour after exercise
- types of amino acid protein: animal source, high leucine
- leucine stimulates protein synthesis
19
Q
How much protein does a pregnant or lactating woman need?
A
30g/day + basal requirement
-need to maintain positive nitrogen balance
20
Q
How much protein does an infant need?
A
2 g/kg/day
-need to maintain positive nitrogen balance
21
Q
What is kwashiorkor?
A
- protein energy malnutrition
- starchy, adequate in calories, protein poor diet (no essential AA intake)
- decreased plasma protein (albumin), poor growth, muscle wasting, edema (due to low serum albumin), diarrhea, increased infections, hair and mental changes, anemia, distended abdomen (fatty liver), flaky paint dermatoses
- negative nitrogen balance
- in children and elderly if do not eat balanced meals
- can be from chronic alcoholism, poverty, self imposed dietary restriction, some hospital settings (trauma or infections)
22
Q
Kwashiorkor vs marasmus? (10)
A
- calories/energy deficiency, fat/muscle wasting kwashiorkor- increase protein in diet
- marasmus- all muscle is used to generate energy
23
Q
What is celiac disease?
A
- genetic disease
- abnormal immune reaction to gluten
- intestinal epithelial cells are damaged and cause malabsorption, steatorrhea, diarrhea, weight loss
- need gluten free diet (treatment)
- gluten is found in insoluble plant proteins found in cereal grains (wheat, barley, rye, oats)
24
Q
Process of digestion of dietary proteins? (13)
A
- in stomach, gastrin in stimulated to release HCl to denature protein to expose peptide bond
- pepsinogen is activated to pepsin in stomach, cuts peptides bonds to make long polypeptides
- in small intestine, secretin will stimulate pancreas to release secretin to release bicarbonate to be transported to small intestine
- bicarbonate neutralizes gastric acid - pancreas will release proteolastase and other enzymes to small intestine
- in small intestine, enteropeptidase will activate trypsin to cut polypeptides into oligopeptides
- in small intestine, amino peptidase will cut oligopeptide to free amino acids
25
Q
what is pepsinogen? function?
A
- inactive (zymogen) form enzyme
- is activated to pepsin by HCl
- pepsin cuts proteins to long polypeptides
26
Q
Gastrin? function?
A
- hormone in stomach is stimulated after food consumption to let parietal cells release Hal
- HCl can denature protein to make them susceptible to hydrolysis by proteases and convert pepsinogen to pepsin (autocatalytic)
27
Q
What activates trypsinogen to trypsin?
A
enteropeptidase
28
Q
What activates the zymogens in pancreas?
A
trypsin
29
Q
Bicarbonate function?
A
- secreted from pancreas under hormone secretin stimulation
- it neutralizes the gastric acid to have intestinal pH around 6-7 for optimal activity of pancreatic proteases
30
Q
What hormone simulates pancreatic proteases?
A
cholecystokinin
31
Q
enteropeptidase? deficiency?
A
- produced in small intestine cells
- hereditary deficiencies cause diarrhea, failure to thrive, and hypoproteinemia
- use pancreatic enzyme supplementation in infancy
32
Q
amino peptidase (di/tri)? function?
A
- from small intestine
- convert peptides to free amino acids
33
Q
summary of digestive enzymes? (14)
A
pic
35
Q
specificity of digestive proteases? (15)
A
- digestive enzymes have different specificity for amino acids R groups adjacent to susceptible peptide bonds
- GI proteases are divided into exopeptidase (cleave end) and endopeptidase (cleave within)
36
Q
Exopeptidases? (15)
A
- cleaves terminal peptide bond
- amino peptidase (amino side of peptide)
- carboxypeptidase A (alanine, isoleucine, leucine, valine)
- carboxypeptidase B (argentine, lysine)
37
Q
endopeptidases? (15)
A
- pepsin (phenylalanine, tyrosine, glutamine, asparagine)
- tyrpsin (arginine, lysine)
- chymotrypsin (tryptophan, tyrosine, phenylalanine, methionine, leucine)
- elastase (alanine, glycine, serine)
42
Q
Process of using glutathione to bring amino acids into cell? (19)
A
- GGT (gamma glutamyl transpeptidase) transports amino acids from outside to inside the cell membrane
- then AA binds gamma glutamyl which is cleaved from glutathione (glutamyl-cysteinyl-glycine) to get into cell
- eventually amino acid dissociates from gamma gluatmyl (no need for energy)
- resynthesis of glutathione (requires energy)
- glutathione reduces oxidative stress
43
Q
Process of Na+ dependent Na+ amino acid cotransporter? (20)
A
- amino acids (luminal side) and Na+ are cotransported into the cell by Na+dependent Na+ amino acid cotransporter
- depends on Na+ concentration gradient (secondary active transporter) - Na+ is pumped out by Na+/K+ ATPase (primary active transporter) with ATP consumption to keep low intracellular Na+ for cotransporting amino acids and Na+
- at serosal side, facilitated transport by amino acid concentration gradient
- low AA in blood, so AA moves from cell to blood down its gradient
- when in fasting state, lower AA in cells than blood, moves opposite way
- AA into cell uses both mechanism, most use cotransporter
44
Q
7 different cotransporters? (21)
A
- at least 7 different Na+ dependent AA carriers in the apical brush border and have overlapping specificity
- neutral AA transporter (BOAT1), 80% of free AA, SLC6A19 gene
51
Q
Removal of nitrogen from AA in metabolism? (26)
A
- recycle for protein synthesis or other nitrogen containing compounds
- removal of N (alpha amino group) liberates C skeleton of AA for producing energy
- high ammonia is toxic, especially can cause brain edema
- normally most of N is converted to urea (nontoxic and soluble) in liver and excreted from urine, small amount of N is converted into NH4+ in urine
54
Q
Step 1: transamination, converting N to urea? (30)
A
- transfer of N from AA to form alanine or glutamine (transporters of N)
- this is a N collection step
- ping pong mechanism- N is juggling back and forth between AA, funnel towards to glutamate
- reversible reaction and equilibrium constant is near 1
- AA 1 becomes keto acid 1
- bidirectional
- two pairs of keto acid/AA involved
- favorite pair: alpha ketoglutarate/glutamate, glutamate is collector or donor
- pyridoxal phosphate (PLP), a derivative of Vit B6, as a cofactor of aminotransferase (transamination, deamination, decarboxylation, beta elimination, racemization, gamma elimination)
55
Q
Two important transaminase reactions? (31)
A
- aspartate aminotransferase (AST)
- alpha ketoglutarate/glutamate -aspartate/oxaloacetate
- PLP
- transfers amino group from glutamate to oxaloacetate and form aspartate, another source of N in urea cycle - alanine aminotransferase (ALT)
- alpha ketoglutarate/glutamate
- alanine/pyruvate (alanine transports N)
- PLP
- transfers amino group from glutamate to pyruvate and form alanine in muscle, which transports N to liver to transfer back to alpha ketoglutarate to form glutamate
- alpha ketoglutarate/glutamate serve as counter keto acid/AA in most transamination reactions
- glutamate is acceptor and donor
58
Q
Ammonia forming reactions? (33)
A
- oxidative deamination of glutamate by glutamate dehydrogenase (removing or fixing alpha N)
- unique reaction only for glutamate, occurs in liver and kidney, GDH in mitochondria
- reversible reaction, directions depending on energy (NAD and NADPH are coenzymes)
- ADP is an allosteric activator of GDH and favors removal of N (ammonia) directly
- GTP, ATP, and NADH are allosteric inhibitors for GDH and favors fixation of N (incorporate N)
59
Q
Disposal and synthesis of AA (glutamate)? (34)
A
- transamination, deamination, amination
1. the sequential action of transamination (amino groups from most AA to form glutamate) and the oxidative deamination of that glutamate will let amino group of most AA to be released as ammonia (NH3)
2. combined actions of reductive amination of alpha ketoglutarate and transamination will synthesize non essential AA - high ammonia levels are required to drive the reaction to glutamate synthesis
61
Q
glucose/alanine cycle? (36)
A
- between muscle and liver for urea synthesis and GNG and bring back to muscle
1. transamination in muscle - form glutamate
2. glutamate transfers N to pyruvate to form alanine
3. alanine carries N to liver
4. in liver, alanine transfer N back to glutamate
5. carbon will be used for GNG to form glucose - back to muscle for energy
62
Q
Glutamine transporter? (37)
A
- carry 2 N for urea synthesis (efficient)
- glutamine synthesis in muscle and peripheral tissues
1. amination to by GDH to glutamate in muscle
2. glutamate to glutamine by glutamine synthetase
3. glutamine transport N to liver for urea synthesis
4. in liver, glutamine releases NH4+ to form glutamate by glutaminase
5. glutamate releases NH4+ to form alpha ketoglutarate by GDH
6. both NH4+ can be used for urea synthesis - glutamine also transports N to kidney releasing NH4+ for excretion of protons, detoxify free ammonia which is produced in tissues
63
Q
summary of urea synthesis? (29)
A
- glutamate is center of urea synthesis
- N carried by alanine and glutamine
1. collect N from AA via transamination
2. alanine and glutamine transport N to liver
3. glutamate collects all N, then release NH3 via deamination
4. aspartate (by transamination) and NH3 provide urea formation
68
Q
Urea cycle process? (39)
A
- in mitochondria, bicarbonate, free ammonia (deaminated from glutamate by GDH), and ATP condense together to form carbamoyl phosphate by CPS 1 (need N acetyl glutamate for activation)
- carbamoyl phosphate will interact with ornithine to form L-citrulline by ornithine transcarbamoylase
- L-citrulline will be transported out to cytosol
- cotransporter: ornithine in, L-citrulline out - L-citrulline will interact with L-aspartate to form argininosuccinate by argininosuccinate synthetase
- cleave it to form fumarate, which leaves, L-arginine forms by arginnosuccinate lyase
- L-arginine is converted to L-ornithine (regenerated) and releases urea by arginase
70
Q
Krebs bicycle? (40)
A
- fumarate gets out of urea cycle and goes to TCA cycle
- turns to malate and further goes through TCA cycle to oxaloacetate
- oxaloacetate goes through TCA, GNG, or can bet converted to aspartate
- OAA becomes aspartate by transamination using glutamate
- aspartate goes back to urea cycle
71
Q
Regulation of urea cycle? (41)
A
- feed forward regulation
- glutamate is high, urea cycle is more activated to remove nitrogen, N acetyl glutamate is also high
- CPS 1 is activated to stimulate urea cycle to turn faster
- arginine stimulates synthesis of N acetyl glutamate, urea cycle goes faster
- high NH4+ is indicator of turning urea cycle
- 3 indicators of increased AA:
1. glutamate
2. arginine
3. NH4+
74
Q
Urea cycle enzyme deficiencies? (43) view handout
A
- arginine is an essential AA in patients with urea cycle enzyme deficiencies
- defect in any urea cycle enzyme will lead to hyper ammonia, along with accumulation of substrate and deficiency of product related to the enzyme
77
Q
Summary? (44)
A
pic
