1
Q
Protein functions
A
- movement
- structure
- participation in and regulate metabolism
- transport
- communication
- protection against infection
2
Q
How do we lose protein
A
- through epithelia
- through urine/feces
- synthesis non-proteion substance
3
Q
Primary structure
A
- linear number and order of amin acids
- based on pairs in the genes that code the protein
4
Q
Secondary structure
A
- folding protein into a-helix or B-sheets or globular or fibrous
5
Q
Tertiary structure
A
- additional folding between R group interactions
- hydrogen bonds, hydrophobic interactions, disulfide bridge, ionic bonding
6
Q
Quaternary structure
A
- interaction between multiple polypeptide chains
- also includes prosthetic groups
7
Q
What are the 9 essential amino acids
A
- histidine
- isoleucine
- leucine
- threonine
- lysine
- methionine
- phenylalanine
- tryptophan
- valine
8
Q
What are the 2 semi-essential amino acids
A
- cysteine
- tyrosine
9
Q
What are the reasons for conditionally essential amino acids
A
- underdeveloped/insufficient synthesis
- increased requirement
- decreased synthesis
- defective synthesis
10
Q
Underdeveloped/insufficient synthesis - conditional amino acids
A
- neonates
- cysteine
- glutamine
- glycine
- tyrosine
- arginine
11
Q
Increased requirement - conditional amino acids
A
- in stress, injuries, surgeries
- glutamine
- DNA biosynthesis, glucose formation, oxidative fuel for immune cells, interorgan transport, rids NH4
12
Q
Decreased synthesis - conditional amino acids
A
- arginine
- synthesized mainly in small intestine and kidney
- preterm infants cannot synthesize it
13
Q
Defective synthesis - conditional amino acids
A
- tyrosine
- lacking enzyme to change phenylalanine to tyrosine
- high amounts of phenylalanine is toxic to brain
14
Q
4 major phases of protein digestion
A
- mechanical digestion
- gastric hydrolysis
- pancreatic proteases
- brush border peptide linkage hydrolysis
15
Q
- Mouth and salivary gland
A
- mechanical digestion
- chewing/crushing/moistening protein rich foods
16
Q
- Stomach
A
- chemical digestion
- gastric juice contains HCl to denature structure and activates pepsinogens to pepsin
- pepsin breaks down smaller peptides to free amino acids and inhibits pepsinogen synthesis
17
Q
- Pancreas and small intestine (duodenum)
A
- polypeptides stimulate CCK release from duodenum
- CCK stimulates pancreas to release pancreatic juice (bicarbonate and enzymes)
- enteropeptidase convert trypsinogen to trypsin
- trypsin activate chymotrypsin, elastase, carbopeptidase, lipase
18
Q
Endopeptidases function and examples
A
- hydrolyze internal peptide bonds within peptide chains
- releases smaller peptides
- ex) trypsin, chymotrypsin, elastase
19
Q
Exopeptidases function and examples
A
- zinc containing
- releases single amino acids from one end
- carboxypeptidase A and carboxypeptidase B
20
Q
Incretins
A
- hormone that stimulates insulin secretion in response to meals
21
Q
2 most important incretin hormones
A
- glucose-like peptide (GLP-1)
- glucose-dependent insulinotropic polypeptide (GIP)
22
Q
Function of DPP-4 and DPP-4 inhibitors
A
- DPP-4 inhibitors (drugs) block DPP-4
- DPP-4 enzyme inactivates incretins
- incretins stimulate insulin release and inhibit glucagon release
- lowers blood glucose
- DPP-4 inhibitors used in diabetes
23
Q
Sources of exogenous and endogenous protein
A
- exogenous: diet
- endogenous: digestive juices, desquamated intestinal cells
- fecal excretion: saliva, gastric juice, pancreatic enzymes
24
Q
3 phases of digestion in intestine
A
- luminal
- membrane
- cytoplasmic
25
What is different in protein brush border absorption
- enzymes can take in tripeptides, dipeptides and amino acids and further breakdown in cytoplasm
26
What are the 6 transport enzyme systems
- brush border peptidases
- brush border amino acid transport system
- brush border peptide transport system
- cytoplasmic peptidases
- basolateral amino acid transport system
- basolateral peptide transport system
27
2 forms of transport exchanger
- H+/peptide cotransporter in apical brush border membrane
- Na+/H+ exchanger in apical brush border membrane
28
5 classifications of amino acid transporters on brush border membrane
- B - neutral AA (Na+) - apical
- B+ neutral and basic AA (Na+,Cl-) - apical
- Y+ basic AA (none) - basolateral
- IMINO imino acids (Na+) - apical
- X- acidic AA (H+, Na+, K+) - apical
29
Sodium-dependent amino acid transport
- important when amino acids is low
30
What part of small intestine has most absorption
- jejunum
31
Products of protein fermentation in large intestine
- BCFAs, ammonia, amines, H2S, phenols, indoles
32
Rate of protein digestion/absorption
- structure (whey vs casein)
- food matrix (fibre)
- oligopeptide vs free amino acid
- neutral before basic/acid
- essential before non-essential
33
2 ways of regulation amino acid absorption
- change in absorptive surface (hyperplasia and hypertrophy associated with obesity, diabetes, pregnancy, lactation)
- change in individual enterocytes (gene expression of peptidases and membrane transporters)
34
How does TPN administration effect absorption
- intestine shrinkage and reduced absorptive capacity
35
Intact protein are generally not absorbed due to
- brush border proteases
- no transporters on basolateral membrane for proteins
- proteins cannot permeate through enterocyte tight junctions
36
Colostrum benefits for newborns
- provides nutrients for growth
- immunoglobins for protection
- growth factors that promote maturation of GI tract
37
What is celiac disease
- gliadin in gluten disrupts tight junctions between epithelial cells
- protease resistant bioactive peptides of gliadin enter ciruclation
- cause immune response, inflammation, and attacks intestinal lining
38
4 roles of enterocytes in amino acid absorption
- pass through enterocyte unmetabolized
- used for protein synthesis in enterocyte
- partially or completely oxidized for energy
- intermediary metabolic conversion
39
3 causes of protein malabsorption
- severe pancreatic dysfunction
- extensive intestinal resection
- severe chronic malnutrition
40
3 metabolic fates of free amino acids in body
- used for protein synthesis in liver
- used as precursors for non-protein nitrogenous molecules
- catabolism with excretion of nitrogen
41
What is transamination
- transfer of amino group to a-keto acid to form new amino acid
- allows body to synthesize non-essential amino acids from essential and non essential amino acids
42
What is oxidative deamination
- nitrogen is lost and amino acid is catabolized
43
glutamate + pyruvate <--ALT-->
a-ketoglutarate + alanine
44
What 8 amino acids are actively transaminated in human tissues
Ala, Asp, Glu, Tyr, Ser, Val, Eli, Leu
45
What 3 amino acids do not participate in transamination reactions
Lys, Thr, Pro
46
Amino groups of many AAs are funneled through which amino acid
Glu
47
Alanine aminotransferase (ALT)
- found mostly in liver but also in kidney, heart, muscle
- cytoplasmic enzyme
- glutamate + pyruvate <--> a-ketoglutarate + alanine
48
Aspartate aminotransferase (AST)
- found mostly in heart but also liver, muscle, kidney
- glutamate + oxaloacetate <--> a-ketoglutarate + aspartate
49
AST/ALT ratio in liver disease
- less than low
- ALT is higher than AST
50
Deamination
- liberation of free ammonia from amino acid coupled with oxidation
- takes place in mitochondria of liver/kidney
- provides NH3 for urea synthesis and alpha keto acids for energy production
- usually glutamate
51
What might increase the urea cycle
high protein diets
- increase enzyme activity/concentration
52
What also might increase the urea cycle
early starvation
- increase activity because proteins are degraded
- if N excretion fails, increase in circulating free ammonia, toxic
53
Low protein diets are given to patients with
renal disease
- kidneys can't excrete urea (build up of toxic nitrogen)
54
Why is ammonia toxic?
- raise pH to damaging level (interferes with electron transport chain, cell damage)
- neurotoxicity
55
Glucogenic amino acids
- C skeletons --> pyruvate or CAC intermediates
56
Ketogenic amino acids
- C skeletons --> acetyl CoA or acetoacetate
- acetyl CoA can enter CAC only if sufficient oxaloacetate
- when short on energy, acetyl CoA pushed to ketone synthesis
57
2 ketogenic amino acids
Lys, Leu
58
What amino acid is used in muscle transamination
- alanine
- alanine --> pyruvate
- pyruvate --> glucose
59
5 steps of protein synthesis
1. DNA transcription
2. RNA processing
3. mRNA stability
4. mRNA translation
5. post-translational protein modifications and folding
60
3 different protein alterations in diseases
- abnormal genes
- abnormal processing of proteins during synthesis
- inability to degrade abnormal proteins
61
SNPs
- single nucleotide polymorphism
- one substitution alters function
62
SNPs - sickle cell anemia
- alters hemoglobin molecule
- deoxygenated proteins polymerize and precipitate within RBC
- sickle shape and cannot carry oxygen
63
SNPs - familial hypercholesterolemia
- defects encoding LDL receptor
- cannot take up cholesterol into cell
- high serum cholesterol
- early atherosclerosis
64
SNPs - connective tissue disorder
- alters collagen structure
- interferes with folding of triple helix or fibril structure
65
SNPs - neonatal diabetes
- improper folded proteins interfere with other cell processes that kill cells that produce insulin
- type 1 diabetes
66
2 importance of protein degradation
- regulation protein abundance
- elimination abnormal proteins
67
4 protein degradation pathways
- ubiquitin-proteasome system (UPS)
- ER-associated degradation (ERAD)
- autophagy-lysosomal pathway (ALP)
- calcium/calpain-dependent system
68
UPS system
- proteins to be degraded are tagged with ubiquitin in ATP requiring reaction
- activity is up-regulated during sepsis, cancer, trauma, starvation
- degraded in proteasome
69
Diseases associated with malfunctioning UPS
- neurodegenerative - Alzheimer's disease (amyloid plaque formation)
- cardiovascular - atherosclerosis (UPS up-regulation gets rid of proteins we need)
70
Autophagy-lysosomal pathway (ALP)
- sequestration, fusion, acidification, digestion
- lysosome contains digestive enzymes (proteases)
- no energy needed
- increased in liver cells by glucagon
71
Parkinson's disease
- UPS and ALP dysfunction
- protein aggregation and death of dopamine neurons
72
Two-compartment model of protein turnover
- free amino acid pool
- body protein pool
73
Two components of N metabolism
- protein turnover (synthesis/degradation)
- nitrogen balance (intake/output)
74
Protein is excreted in
- urine, feces, hair, skin, intestinal cells sloughing, mucus, enzyme secretion
75
Protein turnover accounts for % of BMR
- 10-25%
- energetically expensive
76
Protein turnover is necessary for:
- excretion of nitrogen
- mobilization of AAs
- degradation and replacement of proteins
- changes of protein in response to changes in nutrition and physiological conditions
77
What is main site of AA degradation
- liver
- secondary sites: muscle and small intestine
78
AAs not used for protein/peptide synthesis are
- partially oxidized and C skeletons converted to other compounds depending on body needs
- converted to non-protein derivatives
79
Free amino acid pool is low for
essential AAs
80
Free amino acid pool is high for
Ala, Glu, Gln
81
Why is free pool of essential AAs limited?
must be continually replenished as excess is toxic
- can affect transport into brain
82
Protein catabolic signals
- glucagon, thyroid hormones, glucocorticoids, catecholamines, cytokines
83
Protein anabolic signals
- insulin, amino acids
84
Half lives of regulatory proteins is
- rapid turnover
- GLP and insulin
85
Half lives of non-regulatory enzymes and transport is
- slow turnover
- hemoglobin and albumin
86
Half lives of structural proteins is
- slowest
- collagen
87
Age related muscle loss/atrophy caused by
- anorexia of aging malnutrition - low protein intake
- anabolic resistance physical inactivity - muscle protein dyshomeostatis
88
What can inflammation result in and what are the causes
- muscle wasting
- burns, malnutrition, cancer, sepsis
89
What proteins increase in state of inflammation
- glucocorticoids
- catecholamines
- inflammatory cytokines
- interfere with insulin signaling
90
What happens when you work out your muscles
- muscle stress --> local increase in protein synthesis
91
3 factors that contribute to greater protein synthesis
- energy
- amino acids
- exercise
92
What happens when you ingest essential AAs
- decrease protein degradation
- increase acute systemic protein synthesis
- decrease glucagon and increase insulin
- muscle acts as AA buffer
93
What 2 factors increase anabolism
- hypoxia
- resistance training
94
EAR for protein intake
- males and females 19+
- 0.66g/kg/day
- lowest amount to maintain N balance in body
95
RDA for protein intake
- 0.8g/kg/day
96
Who needs more than RDA for protein intake
- children (highest in less than 6 months)
- pregnancy and lactation
97
AMDR for protein intake
- 10-35%
98
When energy is insufficient, amino acids will be used for...
fuel rather than for protein synthesis
99
When amino acids are oxidized as a fuel, most of their carbon...
enters the TCA cycle and other central pathways of fuel metabolism
100
Inadequate protein -->
decreased protein synthesis
101
Inadequate energy -->
body will utilize dietary protein
102
Acute protein deficiency impacts
- cells with rapid turnover
103
Longer term/chronic deficiency impacts
- all organs especially functions of immune system, small intestine, kidneys, brain
104
Protein nutritional status evaluation by
- plasma proteins
- assessment of rapidly growing tissues (skin and hair)
- lean body mass
105
Marasmus
- energy and protein deficiency
- starvation
- muscle wasting, fat loss, growth retardation
106
Kwashiorkor
- adequate energy and protein deficiency
- more dangerous
- same as marasmus but edema, swollen abdomen, fatty liver, diarrhear, anemia
- decreased synthesis of enzymes and hypoalbuminemia
107
Cautions for high protein diet
- short term: weight loss, calcium loss, ketoacidosis
- rabbit starvation - low amounts of fat and carb
- adverse effects with renal patients
108
2 components of protein quality
- amino acid pattern or score
- digestibility
109
2 components of protein digestibility
- hydrolysis
- availability of AAs - chemical integrity (processing and cooking)
110
True digestibility Dt vs apparent digestibility Da
- Dt is Da corrected for endogenous protein losses
- Da < Dt
111
Animal protein is ___ digestibility and plant protein is ___ digestibility
- high 90%
- lower 70-90%
112
What effects plant protein digestibility
- encapsulated in cell wall and cannot be accessed
- trypsin inhibitors found in legumes and cereals inhibit protein enzymes
113
What factors effect amino acid availability
- food processing and storage
- heat on lysine
- treatment with strong acids
- ultrastructural changes
114
Major factor determining protein quality
amino acid pattern
115
What is amino acid pattern
- most deficient essential amino acid becomes the limiting AA
116
AAs higher than limiting AA get ___ and AAs lower than limiting AA get ___
- oxidized
- protein synthesis
117
Indicator amino acid oxidation method (IAAO)
when 1 indispensable amino acid (DAA) is deficient for protein synthesis, then all other IDAA including the indicator will be oxidized
118
4 major limiting AAs common in foods
- lysine
- methionine
- threonine
- tryptophan
119
Method to assess protein quality
protein digestibility-corrected amino acid scores (PDCAAS)
- AA score x digestibility
- used to determine % daily value on food labels
120
Animal sources contain all essential AAs except
gelatin
- lacks Trp
121
Possible vegan inadequacies
- protein
- Fe, Vit B12, Zn (found in meat and eggs)
- Ca, Vit D, Vit B2 (found in dairy)
- energy
122
Why vegetarian?
- helps maintain healthy body weight and lowers blood pressure
- lowers risk of heart disease and T2D
- meat consumption associated with heart disease, T2D, colon cancer
123
excellent source of protein, very high protein, rich in protein has to have protein rating of
40 or more
124
more protein, higher protein, high in protein has to have protein rating of
20 or more
Nutrition 301
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