After Midterm Flashcards

Question

What is the difference between a peptide and a protein?

Answer 1

A protein is a biologically active version of a peptide. | Proper peptide folding is very important for protein function.

Answer 2

Correct protein folding is assisted by CHAPERONE proteins.

Answer 3

2 AA= Dipeptide 3AA = Tripeptide Around 50AA = Oligopeptide >50 AA = Polypeptide

Answer 4

The primary structure of a protein is determined by the DNA SEQUENCE.

Answer 5

False. | Counting of AAs always starts from the amino end.

Answer 6

Secondary structure of a protein is determined by HYDROGEN bonds that create a stable structure.

Answer 7

False. | Doesn’t involve side chains, only backbone atoms.

Answer 8

1. α-helix • An amino group makes a hydrogen bond with a carboxyl group 4 AAs down the chain, creating a helical shape in the polypeptide chain. 2. β-pleated sheets • An amino group makes a hydrogen bond with a carboxyl group in the folded back polypeptide chain. • Can be parallel or anti-parallel.

Answer 9

Tertiary structure.

Answer 10

1. Binding pockets | 2. Hydrophobic regions

Answer 11

A disulfide bond is an example of an interaction in a TERTIARY structure protein.

Answer 12

A QUATERNARY structure corresponds to a combination of 2 or more TERTIARY structures that are required to make a functional protein

Answer 13

True. | They are quaternary proteins with multiple polypeptides.

Answer 14

False. | NOT all proteins have a quaternary structure.

Answer 15

A native protein corresponds to a protein in its normal 3D configuration.

Answer 16

heat, salt treatment, | detergents, pH (stomach acid)

Answer 17

When a protein is denatured, it loses its bioactivity. Denaturation affects 2°, 3°, and 4° structures (but not 1°). *The peptide chains aren't affected when denatured, it's just the structure that is affected, meaning it's no longer biologically active

Answer 18

Native albumin --> transparent and liquid | Denatured (cooked) --> opaque and hard

Answer 19

1. Essential vs. not essential 2. Basic, acidic, or neutral 3. Polar versus non-polar

Answer 20

1. Essential AA (Indispensable) - Not made by the body or can’t be made quickly enough to meet demands 2. Conditionally Essential - Not normally required in the diet in a healthy individual, but become essential under specific contexts (something happens to the individual for the aa to become essential) 3. Non-Essential (or Completely Dispensable) - Can be synthesized in the body and are not essential in the diet

Answer 21

9 AAs: | lys, thr, iso, leu, met, phe, trp, val, & his

Answer 22

1. Born with a genetic problem: - Phenylketonuria--> an inborn error of metabolism where a person is unable to breakdown Phe into Tyr. • A build-up of Phe in the body causes mental retardation • Solution: limit Phe in diet and supplement with Tyr 2. Develop the problem due to a disease: - Liver disease (cirrhosis) impairs Phe & Met catabolism • Tyr and Cys are synthesized from Phe and Met, respectively • Tyr and Cys become indispensable in this context

Answer 23

1. Polar 2. basic AAs (+ve charge on NH3 group on side chain enables DNA binding) 3. Important in histone proteins, which bind DNA

Answer 24

1. Lysine - Essential - Simple straight chain - Absent from grain products - Lysine Contingency? (Jurassic Park) 2. Arginine -Conditionally Essential -Preterm infants unable to synthesize arginine -Non-essential in healthy adults (as a child grows, it's no longer essential) - Plays an important role in urea cycle 3. Histidine - Essential - Ring structure - Used to produce histamine (inflammation) - Important in children (they can't make it on their own, therefore essential)

Answer 25

1. Acidic AA (-ve charge on side chain carboxyl group) | 2. Acidic AAs are very polar

Answer 26

1. Asparatate - Non-essential - Involved in protein catabolism - Transaminated to oxaloacetate (Krebs) - Donates nitrogen to urea cycle 2. Glutamate -Non-essential -Transaminated to α-ketoglutarate (Krebs) -“Source” of NH3 -Used to produce GABA (neurotransmitter) 3. Asparagine - Non-essential 4. Glutamine -Non-essential -Important in AA catabolism because it is a carrier of nitrogen (to liver & kidney) (amino group is toxic --> can't let it accumulate)

Answer 27

Transamination = passing an amino group from a donor to an acceptor

Answer 28

Transamination = passing an amino group from a donor to an acceptor

Answer 29

1. Neutral AAs (no charge on side chain) 2. Non polar 3. Aliphatic (C & H atoms joined in straight or branched chains)

Answer 30

1. Glycine - Non-essential - No enantiomers - Used primarily to produce porphorin (a component of the heme protein found in hemoglobin) 2. Alanine - Non-essential - Important in AA catabolism because it's a carrier of nitrogen (to liver & kidney) -Important role in glucose-alanine cycle

Answer 31

Glycine has no enantiomers because it has two hydrogen side chains.

Answer 32

1. Neutral aliphatic AAs (no charge on side chain) 2. Non-Polar 3. All are branched

Answer 33

1. Leucine 2. Isoleucine 3. Valine - All are essential - Not catabolized in the liver, so high levels found in circulation -Promotes protein synthesis -BCAA levels are high in protein supplements (not metabolized by the liver, so they go directly to the muscle)

Answer 34

1. OH-group on side chain is important for protein phosphorylation 2. Polar AAs

Answer 35

1. Serine - Non-essential 2. Threonine - Essential Both are important for protein phosphorylation --> allow chemicals to become bioactive

Answer 36

- Contain a sulfur group | - Non-polar

Answer 37

1. Cysteine - Non-essential - Made from methionine “Spares” methionine when cysteine consumed in the diet - Used to form disulfide bonds - Used in glutathione synthesis (oxidant defence system) - could become conditionally essential 2. Methionine - Essential - 1st step in the synthesis of all proteins - Methionine is limiting in legumes

Answer 38

1. Contain Aromatic rings | 2. Non-polar (except tyrosine because of the OH group in its side chain)

Answer 39

1. Phenylalanine - Essential - Used to make Tyr 2. Tyrosine - Non-essential - “Spares” Phe (if tyr is high in diet) - Used to synthesize neurotransmitters 3. Tryptophan - Essential - Used to make serotonin (mood) - Used for niacin (Vit B3) synthesis 4. Proline - Non-essential - Important for collagen production (extracellular matrix) - Aliphatic side chain

Answer 40

PTMs take place in polypeptide chains, not free AA.

Answer 41

1. Phosphorylation by kinase enzymes 2. Hydroxylation 3. Gamma-carboxylation 4. Iodination 5. ADP-ribosyltaion

Answer 42

- Serine-OH - Threonine-OH - Tyrosine-OH Phosphorylation is phosphorus dependent.

Answer 43

1. Lysine --> hydroxylysine - very important in elastin subunits - copper dependent - associated with aortic rupture - Proline--> hydroxyproline - very important in collagen subunits (allows the extracellular matrix to be made; gives tissues their structure) - Vit C dependent - associated with scurvy

Answer 44

- Required for calcium homeostasis and blood clotting - Certain proteins are modified to become Ca2+ binding proteins - Another carboxyl group is added to glutamate - Vitamin K dependent

Answer 45

- Critical in the formation of thyroid hormones - Crucial for regulation of the metabolic rate - Iodine deficiency in about 2 billion humans - Iodine dependent

Answer 46

- Adding ADP-ribose to an acceptor protein - Critical for DNA repair and regulation of protein function - Dependent on Vit B3 (niacin) - Niacin used to form NAD+. When NAD+ is broken down in the cell, ADP-ribose and nicotinamide are the products.

Answer 47

1. Mouth - No enzymatic digestion - Mechanical breakdown only 2. Stomach - HCl in gastric juice (proteins denatured) - Pepsin (endopeptidase) 3. Pancreas -Pancreatic juice containing zymogens (inactive digestive proenzymes) 4. Small Intestine - Zymogens are activated - Enzymes break-down peptides - Absorption of AAs

Answer 48

HCl in the stomach is secreted from PARIETAL cells.

Answer 49

HCl release is triggered by gastrin, acetylcholine, and histamine.

Answer 50

1. Denatures proteins - breaks: hydrogen bonds, electrostatic bonds 2. Activates pepsin

Answer 51

HCl denatures pepsinogen (changes the shape) and then the protein becomes active. (undergoes a proteolytic cleavage)

Answer 52

Pepsin is secreted as PEPSINOGEN, which is an inactive zymogen.

Answer 53

Pepsin is activated in an ACIDIC pH, and inactive at a NEUTRAL pH.

Answer 54

Pepsin is an ENDOPEPTIDASE, i.e., in other words, it cleaves peptide bonds within the polypeptide chain. *This generates mostly oligopeptides and some free AAs.

Answer 55

False. | Polypeptide cleavage occurs not only at ends, but in the middles as well (different length oligopeptides)

Answer 56

Enteropeptidase is located in the brush border. | Enteropeptidase activates trypsinogen to trypsin.

Answer 57

Trypsinogen, chymotrypsinogen, proelastase, procaboxypeptidase A & B.

Answer 58

Trypsin activates other zymogens: Chymotrypsinogen --> Chymotrypsin Proelastase --> Elastase Procarboxypetidases --> Carboxypeptidase

Answer 59

1. Facilitated diffusion 2. Active transport (> 60% of AAs are absorbed this way, it is the dominant system) - sodium-dependent transporters (indirect ATP requirement)

Answer 60

False. | ESSENTIAL AAs are absorbed faster than non-essential AAs.

Answer 61

FREE AAs have no absorptive advantage (i.e. protein supplements) over AAs in FOOD. *Important to consider when incorporating protein supplements into diet, because protein supplements often have BCAA

Answer 62

FREE AAs have no absorptive advantage (i.e. protein supplements) over AAs in FOOD. *Important to consider when incorporating protein supplements into diet, because protein supplements often have BCAA

Answer 63

1. energy 2. synthesis of new protein *Estimates indicate 30-40% of essential AA are used in the small intestine

Answer 64

1. Generate energy for the cell 2. Stimulate cell proliferation (to replace shed enterocytes) 3. Increase synthesis of heat shock proteins (chaperones) 4. Drive mucus production, which helps to prevent bacterial translocation

Answer 65

Liver uses ~20% of the AAs to: - Make new proteins - Make new enzymes - Make albumin and other transport proteins - Make peptide hormones Liver catabolizes the remaining 80% of AAs, where: - NH3 sent to the urea cycle - Carbon skeleton sent to Kreb’s cycle (for energy) or used for gluconeogenesis or lipogenesis

Answer 66

No. BCAAs are not taken up by liver, and instead are anabolic signals for tissues like muscle

Answer 67

1. AA composition 2. Digestibility 3. Presence of Toxic factors 4. Species consuming the protein

Answer 68

Any protein that provides all essential AA = “high quality”. Animal protein > plant protein. Ex. grains are limiting in lysine, legumes are limiting in sulfur-containing AA (methionine).

Answer 69

Some proteins are more digestible than others. More digestible = higher quality. Animal protein > plant protein. Ex. Some materials, like hair, have a great amino acid balance but are indigestible.

Answer 70

Less toxic factors = higher quality. Animal protein > plant protein. Plants contain thousands of phytochemicals. Ex. soybeans contain trypsin inhibitors with interfere with trypsin, thus preventing protein digestion.

Answer 71

Humans, pigs and chickens have similar protein needs. Ruminants have bacteria in the rumen that can make all AAs, so none are considered essential (remember that ruminants can use low quality protein sources).

Answer 72

PER = Official method in Canada for the evaluation of protein quality * With this method, young rats are fed a diet for 4 weeks. The diet has all nutrients present at adequate levels except for protein, which is included at 10% of the diet * 10% protein is marginal for health. If there is anything wrong with the protein source, growth of rats will be impacted * Rats are weighed at the beginning and end of the 4 weeks. Food consumption is carefully monitored

Answer 73

PER = gain in body mass (g) / total protein intake (g) An optimal PER value is 2.0 (2g of rat growth per gram of intake) = whole egg ex. rat gains 10g and eats 14g, PER= 10g/14g = 0.71

Answer 74

- Simple - Cheap - Very sensitive to AA balance, digestibility, toxic factors

Answer 75

* Rats are not humans * Growth, not maintenance * You don’t know WHY a protein is poor quality

Answer 76

CS = - the test protein is chemically digested into free AAs - these are then quantified by chromatography, and mathematically compared to the composition of whole egg protein

Answer 77

CS = (abundance of first limiting AA in test protein / abundance of same AA in whole egg) x 100 ``` ex. CS of wheat % lysine in egg = 7.2 % lysine in wheat = 2.7 (2.7/ 7.2) x 100 = 37 the CS of wheat protein is 37. ```

Answer 78

•Simple and cheap •Identifies the limiting AA in the food •Used to optimize feeds by mixing different sources of protein

Answer 79

* Doesn’t account for digestibility or toxins (e.g. hair) | * Is whole egg an ideal protein?

Answer 80

Nitrogen balance = a measure of N loss (urine, feces, sweat) and N intake (diet) Nitrogen Balance (NB) = Nitrogen Intake – Nitrogen Loss

Answer 81

False. | During growth, pregnancy, and times of tissue repair (NB > 0).

Answer 82

- The problem is worsened with poor protein quality because body proteins are used as a source of essential AA (in other words, body proteins are broken down to “free up” essential AA, ultimately leading to a loss of function) – NB < 0 is seen in people with serious tissue injuries, wasting diseases like sarcopenia, and long-term fasting

Answer 83

True. | This is commonly observed in developed countries like USA.

Answer 84

True. | People are generally in balance.

Answer 85

Protein requirements are higher during infancy, childhood, teenagers, and during pregnancy & lactation.

Answer 86

True. Plant sources may be less digestible due to differences in the nature of protein and other components (fibre). If recommendations used plant sources of protein, the values would be higher.

Answer 87

1. High protein diets (Atkins, South Beach) | 2. Protein Supplementation

Answer 88

1. Deficient in both protein quantity and energy (overall malnutrition) 2. Deficient in only protein quantity

Answer 89

1. Atkins Diet (most criticized) (C:F:P = 3:64:33) - Different phases where macronutrient content varies. - CHO intake very low, while fat and protein intake very high (~30% protein). - Criticized because no attention to type of CHO or fat consumed. 2. South Beach diet (C:F:P = 30:40:30) - Different phases where macronutrient content varies. - For CHO intake there is an emphasis on low GI foods. - Protein is consistent throughout the various phases (~30%) 3. The Zone Diet - Not really a high protein diet, rather a balanced diet.

Answer 90

False. All high protein diets NOT created equal – Huge differences in macronutrient content and the types of CHO/fats consumed, so it’s hard to compare outcomes.

Answer 91

1. short term weight loss is comparable to other diet approaches. 2. Some studies show improved insulin sensitivity with high protein as compared to high CHO diets (probably due to reduced burden on the pancreas to generate insulin). 3. Conflicting results with respect to effect on cardiovascular disease. A moderate increase in protein appears to be cardioprotective, but high protein may be a concern in the long-term. 4. People with kidney diseases should avoid high-protein diets.

Answer 92

True. HOWEVER, this would be the same if a person ate a high quality protein (eggs, meat, fish).

Answer 93

Most protein supplements deliver high levels of BCAAs, are rapidly absorbed and delivered to the muscle.

Answer 94

Anabolic response of the muscle to a protein meal gradually diminishes after 40 years of age. *this can be improved with BCAA supplements

Answer 95

MARASMUS is a protein and energy deficiency.

Answer 96

- Very low intake of a balanced diet with around 8-10% protein (so just a bit below what is needed). - Because everything is in balance, the body switches to starvation mode. - Well organized utilization of body fuel stores allows survival, eventually leading to a complete loss of body fat which causes a wrinkled appearance to the skin Characterized by: complete loss of body fat and muscle, peeling skin, uneven pigmentation

Answer 97

KWASHIORKOR is a protein deficiency.

Answer 98

- Diet has sufficient Calories, but is deficient in protein (Only 1-2% protein in the diet) - Typically seen in developing countries where agriculture is key - High CHO foods (e.g., tuber cassava) – When child is weaned from mother’s breast milk (very balanced source of nutrients) to cassava porridge (no protein or fat) – Lots of CHO, but no protein to metabolize or transport nutrients Characterized by: enlarged abdomen, ‘burns’ on the skin and diarrhea

Answer 99

1. Decreased plasma proteins causes an osmotic imbalance in the gut (edema); leads to a swelling of the gut 2. Liver is enlarged due to the inability to export fat from the liver (can’t make VLDL)

Answer 100

1. Variable protein/energy restriction: When the dietary challenge fluctuates over time (i.e., feast and famine). -People typically survive these challenges, but can be quite ill for several months of the year. 2. Acute protein/energy restriction: When a severe dietary challenge sets in. -If there is no change, then this would cause death after 1-2 months.

Answer 101

False. | BOTH Marasmus & Kwashiorkor lead to immune dysfunction.

Answer 102

True. | Lect. 11, slide 2

Answer 103

Most AAs derived from protein breakdown are reused to make new protein, while a little is catabolized. (made from carbon skeleton or ammonia)

Answer 104

1. Fasted state involves the formation of both glutamine and alanine, while the fed state is primarily glutamine. 2. Fed state involves both the liver and kidneys. 3. Fed state involves the excretion of NH4 + as urea, whereas the fasted state involves the excretion of ammonium (NH4 +) directly.

Answer 105

1. The liver converts the amino group to urea in a process that uses HCO3- 2. Metabolism of Sulfur-containing AA produces a bit of sulphuric acid to neutralize pH

Answer 106

1. The liver converts the amino group to urea in a process that uses HCO3- 2. Metabolism of Sulfur-containing AA produces a bit of sulphuric acid to neutralize pH

Answer 107

1. minor amounts of protein are catabolized to release glucogenic amino acids (for gluconeogenesis) - however the primary source of energy is fat (TAG) 2. The breakdown of TAG leads to the production of acidic ketone bodies *The brain will start to use ketone bodies instead of glucose, but there is production of a slightly acidic molecule

Answer 108

Long-term fasting encourages a slight ACIDOSIS (pH can DROP to 7.0). This is also known as nutritional KETOSIS.

Answer 109

Products of TAG breakdown (long hydrocarbon chains) are not very water soluble. The liver converts these long hydrocarbons into small soluble ketone bodies (which the brain can uses for energy during starvation).

Answer 110

When AAs are catabolized in the fasted state, the amino group is brought directly to the kidney (thus bypassing the urea cycle where HCO3- is used up.) This means that HCO3- produced in the Kreb's cycle can be used to neutralize the weak acidosis state caused by ketones.

Answer 111

When AAs are catabolized in the fasted state, the amino group is brought directly to the kidney (thus bypassing the urea cycle where HCO3- is used up.) This means that HCO3- produced in the Kreb's cycle can be used to neutralize the weak acidosis state caused by ketones.

Answer 112

1. Glutamate 2. Aspartate 3. Alanine 4. Glutamine

Answer 113

1. Incredibly important in AA catabolism 2. It is a common end product of transamination reactions - α-ketoacid for glutamate is alpha-ketoglutarate

Answer 114

1. Donates an amino group in the urea cycle | - α-ketoacid for asparatate is oxaloacetate

Answer 115

1. Inter-organ nitrogen carrier (goes to liver) | - α-ketoacid for alanine is pyruvate

Answer 116

1. Most abundant AA in the body 2. Inter-organ nitrogen carrier (goes to liver & kidney) 3. Can donate a NH3 group to other reactions

Answer 117

1. Transamination 2. Oxidative deamination 3a. Glutamine production 3b. Glutamate Regeneration 4. Urea cycle

Answer 118

1. Transamination 2. Oxidative deamination 3a. Glutamine production 3b. Glutamate Regeneration 4. Urea cycle

Answer 119

Transamination = transfer of an amino group to an AA carbon skeleton (i.e., α-ketoacid) --> catalyzed by “aminotransferases”

Answer 120

most AA undergo transamination (except lysine, proline, and threonine)

Answer 121

PYRIDOXAL PHOSPHATE (active form of Vit B6) is the coenzyme that holds the NH3 group during transamination.

Answer 122

1. Bi-directional reactions 2. Active in all tissues 3. Always produces an AA (usually glutamate) and α-ketoacid 4. At least 1 transaminase exists for each AA, with each using glutamate/ alpha-ketoglutarate as one of the pairings

Answer 123

1. Glutamate pyruvate transaminase (GPT) (also known as ALT) Alpha-ketoglutarate + alanine --> Glutamate + Pyruvate 2. Glutamate oxaloacetate transaminase (GOT) (also known as AST) Alpha-ketoglutarate + Aspartate --> Glutamate + Oxaloacetate

Answer 124

Glutamate is the main AA to undergo oxidative deamination. | Because glutamate is the main product of transamination.

Answer 125

1. NH3 is released from the glutamate backbone 2. Reaction favours the formation of alpha-ketoglutarate 3. A process that is very active in all tissues in the body *This is a point in the pathway --> how to get the amino group out of glutamate

Answer 126

1. Extrahepatic tissue (EHT)--> the NH4+ is used in the synthesis of glutamine 2. Liver--> NH4+ is used for urea synthesis 3. Kidneys-->NH4+ is excreted directly as is into urine

Answer 127

1. Formation of glutamine (primary inter-organ nitrogen carrier) 2. Muscles are the main producer of glutamine (produces ~90% of the glutamine found in the body)

Answer 128

Glutamine synthetase.

Answer 129

Fed state --> travels to liver | Fasted state --> travels to kidney

Answer 130

1. Opposite reaction to glutamine production; however, a different enzyme is required 2. Releases NH3 (NH4+) from the glutamine side chain (i.e., deamination) 3. Active in liver in the fed state (NH3 used for urea synthesis) 4. Active in the kidney during fasting (NH3 secreted as NH4+)

Answer 131

Glutamate regeneration.

Answer 132

Glutaminase.

Answer 133

1. Toxic NH4+ is converted to less toxic urea in the liver | 2. Urea transported to kidney for excretion

Answer 134

Fasted state: 80-90% of urinary N will be in the form of NH4+. Fed state: 80-90% of urinary N will be in the form of UREA.

Answer 135

1. Oxidative deamination | 2. Glutamate regeneration from glutamine

Answer 136

In the urea cycle, aspartate condenses with CITRULLINE and DONATES an amino group.

Answer 137

The urea cycle uses HCO3-, thereby preventing ALKALOSIS.

Answer 138

Defects lead to developmental neurotoxicity due to a build-up of NH4+ in the body.

Answer 139

Cahill cycle.

Answer 140

For every glucose, you get 2 alanine. 1 glucose = 2 pyruvates; each pyruvate undergoes transamination to alanine

Answer 141

Fed state: - non-liver protein catabolism leads to glutamine formation (from glutamate). - Glutamine is transported to the liver, where it delivers an amino group for urea production. - Urea is then transported to the kidney and excreted in urine.

Answer 142

Fasted state: - non-liver protein catabolism leads to glutamine formation (from glutamate) and alanine (from pyruvate). - Glutamine is transported directly to the kidney, while alanine is sent to the liver (for gluconeogenesis). - In the kidney, glutamine is converted to glutamate and the removed amino group is excreted in urine as NH4+.

Answer 143

When body’s energy sources are low, protein is broken down. AA catabolism releases (1) AMINO GROUP (NH3), and (2) α-KETOACID.

Answer 144

1. Deamination --> removal of amino group from AA. The carbon skeleton that remains is the α-ketoacid (mostly seen with glutamate). 2. Transamination --> transfer of an amino group from an AA to an α-ketoacid. In the process, the “donating” AA becomes an α-ketoacid and the “receiving” α-ketoacid becomes an AA.

Answer 145

α-ketoacids contain KETONE and CARBOXYLIC ACID functional groups.

Answer 146

Ketogenic --> a degraded AA that can be converted into Acetyl CoA

Answer 147

Glucogenic --> a degraded AA that can be converted into Glucose.

Answer 148

1. Acetyl CoA (leucine) 2. Acetoacetyl CoA (lysine) (lecutre 11 slide 19)

Answer 149

1. Pyruvate 2. α-ketoglutarate 3. Succinyl-CoA 4. Fumarate 5. Oxaloacetate

Answer 150

Intermediates with 3 to 6 carbons can be used to make glucose.

Answer 151

Because Acetyl CoO is purely ketogenic.

Answer 152

To burn fat, you must have an active Kreb’s cycle, which depends on availability of oxaloacetate (a CHO). *Doesn't matter how much fat you have, if you don't have oxaloacetate there won't be any energy production.

Answer 153

False. | Burning fat is NOT a problem when glycogen is present (have oxaloacetate).

Answer 154

When glycogen is depleted, you have GLUCONEOGENESIS to maintain blood glucose. (from glycogenic AA catabolism)

Answer 155

Oxaloacetate is a gluconeogenic precursor, so if something ELSE isn’t doing this job, oxaloacetate will be used to make glucose and the Kreb’s cycle slows and can’t burn fat.

Answer 156

Blood glucose: between 60-100mg/dL (<60mg/dL you develop a coma and die) Blood pH: near neutrality (related to amino group handling)

Answer 157

1. always required by RBC as energy substrate (no mitochondria) 2. required by central nervous system (brain)0 (although gradual adaptation to ketones is possible) 3. maintaining an active Kreb’s cycle

Answer 158

1. Fed -Dietary CHO (if high carbohydrate diet) -Dietary protein (if high protein diet) (any leftover AAs are used) 2. Post-absorptive (no food left in GIT) - Glycogen from liver (direct) and muscle (indirect) 3. Fasting (no glycogen) (after 24 hours) - Gluconeogenesis from protein catabolism (only in liver) 4. Starvation (several days, have biochemical adaptations) -Gluconeogenesis from glycerol produced by TAG breakdown; some protein catabolism

Answer 159

Macronutrient flux --> the way our body is using carbs, fats, proteins

Answer 160

Macronutrient flux is regulated by multiple TISSUES and numerous HORMONES.

Answer 161

Short-term = (minutes to hours) i.e., between meals Tissue crosstalk: - Hormones move throughout the body and activate signalling pathways in their target tissues (e. g. insulin, glucagon, epinephrine, etc.) - Hormones usually affect protein function (e. g. phosphorylation or de-phosphorylation of enzymes) * This occurs rapidly because protein is already made and waiting for modification

Answer 162

Long-term = (several hours to days) i.e., fasting, starvation – Affects gene expression *Cell says "i need to start making different proteins that will allow me to respond in different ways"; it needs to make rna, translate, etc. this takes a lot of time

Answer 163

1. Insulin - Anabolic - Pancreas (β-cells ) 2. Glucagon - Catabolic - Pancreas (β-cells ) 3. Corticosteroids (cortisol) - Catabolic - Adrenal Cortex 4. Catecholamines (epinephrine) - Catabolic - Adrenal medulla

Answer 164

↑ glucose and AA uptake in muscle and liver ↑ glycogen and protein synthesis in muscle and liver; ↑ fat synthesis and storage

Answer 165

↑ breakdown of glycogen, protein & fat | ↑ gluconeogenesis from AAs and glycerol

Answer 166

↑ Muscle protein catabolism | ↑ gluconeogenesis from AAs

Answer 167

↑ glycogenolysis and lipolysis | at the level of adipose tissue

Answer 168

The brain has a high requirement for OXIDATIVE METABOLISM to support its continuous electrical activity.

Answer 169

100-120g of glucose per day

Answer 170

Fatty acids can't cross the blood-brain barrier enough to provide sufficient energy (ketone bodies CAN cross but it requires adaptation)

Answer 171

Brain consumes about half of this.

Answer 172

False. | The liver DOES regulate blood glucose levels.

Answer 173

Extra carbs get converted into Fatty Acids. Insulin sends glucose to acetyl coA, acetyl CoA is turned into FA. Glucose --> pyruvate --> acetyl coA --(ACC) --> Malonyl CoA --> Fatty Acid

Answer 174

1. Fatty acids (FAs) from diet and de novo lipogenesis | 2. Only tissue to produce ketone bodies (*critical during starvation)

Answer 175

False. Adipose tissue has a LOW energy requirement, therefore NOT A LOT of oxidative fuel consumption. *doesn't need a lot of energy to perform its function of storing fat

Answer 176

1. For TAG synthesis | 2. Provides energy for fatty acid uptake (via LPL)

Answer 177

•Releases non-esterified fatty acids (NEFA) into circulation (from lipolysis) - Depending on circumstances, NEFA can be a major metabolic fuel for the body - NEFA are the same thing as “free fatty acids” *Notice that lipolysis occurs in adipose tissue.

Answer 178

Skeletal muscle represents around 40% of body weight.

Answer 179

1. Nutritional status | 2. Exercise

Answer 180

1. Slow-twitch - Used for long duration activity, slow contraction - Predominant source of energy = Fatty acids (i. e., NEFA from adipose tissue) 2. Fast twitch - Used for short duration activity, quick contraction - “Local” glycogen stores = energy source

Answer 181

``` (e.g. weight-lifting and sprinting) • hormones are too slow to act • signal = Ca2+ release • energy released from: - muscle glycogen stores - muscle creatine phosphate ```

Answer 182

(e.g. jogging) • diffusion of substrates & O2 from blood • slow process • energy released from complete oxidation of glucose and fatty acids

Answer 183

1. low-to-moderate intensity exercise--> fatty acids are the primary source of energy 2. high intensity exercise--> glucose is the primary source of energy

Answer 184

False. The Gastrointestinal tract has a HIGH rate of cell turn-over, so energy is needed to allow for protein synthesis and production of DNA/RNA to make new cells.

Answer 185

In the small intestine: Glutamine (AA) is the main source of energy (converted to α-ketoglutarate, an intermediate in the Kreb’s cycle)

Answer 186

In the large intestine: SCFA from bacterial fermentation are also used for energy (Particularly butyrate)

Answer 187

1. "Precious" glucose is used quickly 2. Glycogen reserves last for 24 hrs, and are then depleted 3. Protein breakdown occurs initially, releasing glucogenic amino acids - This slows down to preserve protein function, but continues to provide what is needed to maintain Kreb's cycle activity 4. Fatty acid breakdown occurs to “spare protein”; eventually used to make ketone bodies

Answer 188

1. High blood glucose 2. Insulin secreted from pancreas 3. Glucose uptake and glycogen formation promoted in liver and muscle

Answer 189

1. AA are catabolized by liver - BCAA go directly to the muscle and promote protein synthesis 2. Glutamine carries nitrogen to the liver from every tissue in the body that is catabolizing AAs - Urea is produced, thus preventing alkalosis conditions (use up HCO3-)

Answer 190

1. Lipid uptake into adipose tissue

Answer 191

1. Blood glucose maintained by glucagon, which increases hepatic glycogen breakdown 2. Liver secretes glucose 3. Necessary to maintain blood glucose for RBC and brain 4. Blood glucose supports Kreb’s cycle in all tissues

Answer 192

1. Muscle secretes alanine, which goes to the liver (glucose-alanine cycle)

Answer 193

1. Fat not yet used as a source of energy

Answer 194

1. Glycogen pools are empty 2. RBC and brain still require glucose for energy 3. Blood glucose supports Kreb’s cycle in all tissues 4. Glucose-alanine cycle active (liver secretes glucose)

Answer 195

1. Corticosteroids secreted from adrenal gland promote more protein catabolism - Mostly in muscle, but also gut 2. Glucogenic AAs are used to make glucose in liver (Glucose-alanine cycle active) 3. Alanine and glutamine carry nitrogen (i.e., amino group) - ~50/50 mix between urea and ammonia (kidney)

Answer 196

1. Fat starts to be used for energy

Answer 197

1. Liver produces ketones, which promotes a slight acidosis | 2. Glucose-alanine cycle active

Answer 198

1. Liver produces ketones, which promotes a slight acidosis 2. Still have to maintain Kreb’s cycle with protein catabolism (i.e., glucogenic amino acids) 3. Glutamine carries nitrogen directly to kidney (allows HCO3- to be used to buffer against acidic ketone bodies) 4. Glucose-alanine cycle active

Answer 199

1. Body switches primarily to fat usage for energy 2. Glucagon and catecholamines regulate adipose tissue lipolysis 3. Fat is predominantly ketogenic (only the glycerol backbone is glucogenic) 4. Tissue metabolism adapts to “spare” protein loss

Answer 200

Long term starvation leads to MARASMUS.

Answer 201

Exhaustion is due to loss of glycogen pools; this leads to a drop in blood glucose or failure of tissue Kreb’s cycle activity (drop in oxaloacetate)

Answer 202

1. Carbohydrate loading while resting - Can double muscle glycogen reserve - Delays failure of the Kreb’s cycle 2. Fasting for 3hr prior to start - Avoid insulin secretion--> higher glucagon 3. Consume supplementary CHO during the event - Ex. someone running the Ironman requires around 5000 kcal during the event 4. Caffeine (ergogenic aid) - Stimulates an early release of epinephrine, which activates HSL to promote adipose tissue lipolysis

Answer 203

No. It depends on genotype. People with CC genes (slow breakdown) may actually do worse when given caffeine than without.

Answer 204

1. Exogenous supply is required (can't make on our own) 2. Needed in small amounts 3. Distinct from sugars, fats and proteins in regard to structure and function 3. Perform at least one essential biochemical function in the body 4. When lacking in the diet, a characteristic deficiency disease develops 5. Vitamins are organic - Primary distinction from minerals (which are inorganic)

Answer 205

The functional groupings allow us to talk a little bit more about the bioactivity of vitamins and minerals.

Answer 206

1. Group I: Micronutrients that control type II steroid hormone receptors and have major global health implications ex. Iodine, Vit A, Vit D, Calcium, Vit K, Phosphorus and Fluoride 2. Group II: Micronutrients that work together in oxidant defense ex. Vit E, Selenium, Vit C, Niacin, Riboflavin, Copper, Zinc, Manganese 3. Group III: Micronutrients that act as enzyme cofactors ex. Thiamin, Niacin, Riboflavin, Vit B6, Folate, Vit B12, Biotin, Pantothenic acid 4. Group IV: Iron, copper, and zinc-related divalent cations

Answer 207

These micronutrients control cellular function through type II steroid receptors.

Answer 208

True. Only the bioactive forms of Vit A, Vit D, and iodine act directly on steroid hormone receptors (But we can’t talk about Vit D without talking about calcium, phosphorus, and Vit K since they are all involved in bone metabolism)

Answer 209

Iodine used to make T3 hormone, which regulates synthesis of proteins that control a person’s basal metabolic rate

Answer 210

Vit A precursors are converted to retinoids, which regulate night vision, epithelial differentiation, and gene expression

Answer 211

Vit D precursors are converted to calcitriol, which regulates calcium levels in the body

Answer 212

Steroid Hormone Receptors --> intracellular protein receptors They need to bind a ligand to become a functional (active) transcription factor

Answer 213

Type 1 Receptors: Cytosolic - Respond to steroid hormones like estrogen, testosterone, progesterone, glucocorticoids, and mineralcorticoids (We won’t discuss this type) Type 2 Receptors: Nuclear - Respond to steroid & non-steroid ligands, like thyroid hormone, retinoic acid, and calcitrol

Answer 214

False. | NOT all ligands are derived from steroids.

Answer 215

Iodine is an INORGANIC mineral that is highly WATER soluble.

Answer 216

True. | Seafood has high concentrations of iodine (especially sea greens)

Answer 217

In North America, most of the iodine consumed comes through “salt fortified with potassium iodine” - Iodized salt contains 0.03mg iodine per g of salt

Answer 218

False. | Dietary iodine can be bound to amino acids or found free.

Answer 219

In our gastrointestinal tract, iodine (I) is rapidly converted to iodide (I- , its ionic form) and absorbed - Most is absorbed in the stomach, and a bit in small intestine

Answer 220

In the blood, free I- circulates and can enter all tissues; however, most accumulates in the thyroid gland (70-80% of the iodine in our body is in the thyroid gland)

Answer 221

Uptake of I- in the thyroid gland is mediated by an ACTIVE transport system known as the Na+/I- SYMPORTER (NIS).

Answer 222

False. | • All tissues depend on thyroid hormones (T3 and T4) rather than iodide itself

Answer 223

• Once T3 and T4 are made, they are released into blood and transported by specific carrier proteins (albumin, transthyretin, etc.)

Answer 224

50× more T4 in blood compared to T3.

Answer 225

T3 is 100× more potent.

Answer 226

T3 half-life < T4.

Answer 227

T3 interacts with thyroid hormone receptor (THR).

Answer 228

T3 and T4 production is regulated by TSH (thyroid stimulating hormone).

Answer 229

When T3 blood levels are low, the HYPOTHALAMUS signals to the pituitary to release TSH.

Answer 230

Iodide radical attacks the TYROSINE residue of the thyroglobulin. *This causes the cross-linking between tyrosine residues

Answer 231

The colloid (lumen) of the thyroid cell.

Answer 232

Thyroid cell proteases hydrolyze THYROGLOBULIN, releasing fragments that correspond to T3 and T4 hormones.

Answer 233

Thyroid hormones influence how your body stores and uses energy (i.e., affects metabolism).

Answer 234

- Breathing - Heart function - Nervous system function - Body temperature - Cholesterol level - Energy balance - Brain development - Moisture in the skin - Menstruation

Answer 235

True. | This means they can easily cross plasma membranes.

Answer 236

True. | This mainly occurs in the liver (but can occur in other tissues too).

Answer 237

T3 + THR (thyroid hormone receptor) --> bind to response element in the promoter region of DNA --> activate gene expression (mRNA) *Note: THR is already in the nucleus

Answer 238

1. ATPases (pump Na+ and Ca2+ out of cells), which increases metabolic rate - Na+ (muscle contraction, neuron firing) - Ca2+ (signaling events) 2. Growth hormone (anabolic effects)

Answer 239

``` Adipose Tissue --> lipolysis Muscle --> contraction Bone --> promotes making bone Heart --> Increases heart rate GIT --> stimulates nutrient digestion ```

Answer 240

When T3 levels are LOW, the pituitary gland releases TSH (thyroid stimulating hormone).

Answer 241

1. Hyperplasia (↑ cell #) 2. Hypertrophy (↑ cell size) *Protein is still being produced, which grows the cell.

Answer 242

1. Goiter (in adults) --> thyroid enlargement - Can be treated with iodine supplements - If left untreated, becomes thyroid cancer 2. Cretinism --> when iodine levels are low in mother, the fetus doesn’t develop properly - Growth & developmental abnormalities - Irreversible - 50 million people have some degree of mental impairment caused by IDD (WHO).

Answer 243

They measure it through urine (iodine is water soluble).

Answer 244

Through fortification. ex. salt

Answer 245

It helps with thyroid gland support.

Answer 246

Vitamin A supports night vision, eyesight, and skin health.

Answer 247

Ancient Egyptians and Greeks realized that LIVER could cure night blindness. *egyptians squeezed it into their eyes, greeks ate it

Answer 248

Originally named fat soluble A because egg yolk contains a fat soluble material that is necessary for life.

Answer 249

Vitamin A is a general term used to refer to a group of compounds known as RETINOIDS.

Answer 250

Major forms of Vitamin A in the body are: | retinol, retinal, retinoic acid, & retinyl ester

Answer 251

The alcohol form, RETINOL, was first identified and then CAROTENE were recognized as the plant form of Vitamin A.

Answer 252

False. | In plants, carotenes are pro-vitamins used for pigmentation. In animals, vitamin A is bioactive.

Answer 253

Carotenes (provitamin A) are PRECURSORS for Vitamin A.

Answer 254

They are pigments produced in plants (e.g. β-carotene, α-carotene, etc.)

Answer 255

Milk, eggs.

Answer 256

RETINYL ESTER = retinol + fatty acid

Answer 257

For absorption, a RETINYL ESTERASE must cleave the fatty acid from retinol (in a retinyl ester)

Answer 258

Essentially nothing. β-carotene can be absorbed just like that.

Answer 259

Both retinol and β-carotenes are LIPOPHILIC compounds, therefore incorporated into mixed micelles.

Answer 260

Both are absorbed by passive diffusion.

Answer 261

1. Converted into a retinyl ester in the intestinal cell then incorporated into chylomicrons 2. Incorporated “as is” into chylomicrons

Answer 262

1. β-carotene can be packaged into VLDL and sent for storage in adipose tissue. 2. Retinyl esters (e.g., retinyl palmitate) are stored in hepatic stellate cells until needed *When needed, liver retinyl esterase removes FA, releases retinol to bind to RBP and secreted into blood*

Answer 263

Low levels of retinol-RBP stimulate the liver to release retinyl esterase.

Answer 264

β-carotene comes from plants, which have higher fiber levels than animal products. Fiber reduces the rate of absorption.

Answer 265

In the intestine, β-carotene can be broken down into TRANS RETINAL (aldehyde) by the enzyme 15,15’-CAROTENOID DIOXYGENASE.

Answer 266

All trans retinal can be converted to trans retinol by RETINOL DEHYDROGENASE.

Answer 267

False. The retinol acts like a detergent, which is UNSAFE for a cell. So retinol is converted into a retinyl ester (safer for the cell).

Answer 268

Nothing. Retinyl esters have no direct function in the body.

Answer 269

All trans retinal can be converted into TRANS RETINOL or RETINOIC ACID (directly).

Answer 270

Night vision.

Answer 271

1. Rod cells use rhodopsin to absorb light (greyish purple colour) 2. Opsin + 11-cis retinal combine to become rhodopsin, which is light-sensitive (night sensitivity causes neuron signalling = vision) 3. When light hits rhodopsin, it reforms all trans retinol

Answer 272

Isomerase introduces a KINK to all-trans retinal when it converts it to 11-cis retinal.

Answer 273

In the cytosol, retinol is converted into retinoic acid.

Answer 274

RA --> into nucleus --> binds to and activates RAR & RXR transcription factors --> complexes homo- & hetero-dimerize with other NHR --> creates a large number of possible TF combinations --> allows regulation of gene expression *RAR --> retinoic acid receptor RXR --> retinoid X receptor NHR --> nuclear hormone receptors

Answer 275

1. Night blindness (lack of rhodopsin) - Reversible, one of the first signs of Vit A deficiency - Associated with Bitot’s spots, a buildup of keratin debris in the conjunctiva of the eye 2. Impaired epithelial cell differentiation - Can cause permanent blindness and life threatening infections 3. Impaired growth (growth hormone not produced) - Impacts bone development, tooth decay, etc. 4. Impaired fertility - Decreased sperm formation, fetal resorption (early death of embryo) 5. Fetal development defects - Birth defects due to loss of control of differentiation - Can occur with too little OR too much Vit A

Answer 276

1. Night blindness (lack of rhodopsin) - Reversible, one of the first signs of Vit A deficiency - Associated with Bitot’s spots, a buildup of keratin debris in the conjunctiva of the eye 2. Impaired epithelial cell differentiation - Can cause permanent blindness and life threatening infections 3. Impaired growth (growth hormone not produced) - Impacts bone development, tooth decay, etc. 4. Impaired fertility - Decreased sperm formation, fetal resorption (early death of embryo) 5. Fetal development defects - Birth defects due to loss of control of differentiation - Can occur with too little OR too much Vit A

Answer 277

RAE = Retinol Activity Equivalents RAE accounts for differences in the biological activity of carotenoids 1 RAE = 1 μg dietary retinol = 12 μg dietary β-carotene = 24 μg other carotenes

Answer 278

Men --> 900 μg/d RAE | Women --> 700 μg/d RAE

Answer 279

UL = 3000 μg/d RAE

Answer 280

Carotenoids prevent deficiency, but don’t cause toxicity. 15,15’-carotenoid dioxygenase regulated by Vit A status. If you have enough Vit A, carotenoids aren’t converted to retinol, but are stored “as is”. (Carotenoids are stored in the inactive form and are converted when needed, but retinol is always in the active form and can cause toxicity.)

Answer 281

Most severe consequence is liver cell death.

Answer 282

Retinyl esters are stored in the stellate cells of the liver and with excess Vit A intake, the cells get full to capacity. Raw Vit A spills out and the local hepatocytes become damaged and die.

Answer 283

Excessive intake of β-carotene can cause hypercarotenosis (skin turns yellow-orange).

Answer 284

It was shown to cause birth defects in women in the early months of pregnancy.

Answer 285

It was shown to cause birth defects in women in the early months of pregnancy.

Answer 286

You would have Vit A toxicity. Human liver has ~170 RAE/g Polar bear liver has ~10,000 RAE/g

Answer 287

Supports a healthy immune system and bone health.

Answer 288

Although Vit A and Iodine deficiencies are prevalent in the developing world, VITAMIN D is the most prevalent micronutrient deficiency in the developed world.

Answer 289

1. Made in one tissue (kidney) and acts on other tissues | 2. Works with other hormones such as parathyroid and calcitonin

Answer 290

Rediscovered the use of cod liver oil to prevent bone diseases.

Answer 291

This indicated that fat soluble Vit D can also be synthesized in the body.

Answer 292

1. Natural Plant Sources (Provitamin D2) 2. Natural Animal Sources (Provitamin D3) 3. Sunlight 4. Supplementation 5. Fortification

Answer 293

1. Natural Plant Sources (Provitamin D2) 2. Natural Animal Sources (Provitamin D3) 3. Sunlight 4. Supplementation 5. Fortification

Answer 294

- Shitake mushrooms - It's not very active in plants, so not a great source of Vit D *Ergocaliferol is less bioactive than cholecalciferol

Answer 295

After irridation, ergosterol (provitamin D2) turns into ERGOCALCIFEROL (vitamin d2).

Answer 296

Fish, fish liver oils

Answer 297

• 7-dehydrocholesterol (7-D) is converted to CHOLECALCIFEROL (Vit D3) by sunlight (UVB and infrared) This occurs in sebaceous glands of skin.

Answer 298

False. | This occurs as soon as you go out in the sun.

Answer 299

Vit D3 binds to the Vitamin D binding protein.

Answer 300

These molecules are inactive, and are eventually lost as we shed skin. *Note: Luminesterol and tachysterol can also be converted back into 7D.

Answer 301

MELANIN in the epidermis absorbs UV rays, which can limit Vit D3 production. *This was part of the problem for population deficiencies over time (migrating populations).

Answer 302

We should use Vit D3 (cholecalciferol). This is especially important for someone who spends lots of time indoors.

Answer 303

No. | It is insufficient for health if this is a person’s only source of Vit D3.

Answer 304

No. | It is insufficient for health if this is a person’s only source of Vit D3.

Answer 305

There is no risk.

Answer 306

It can go to: • Liver (conversion) • Adipose (storage)

Answer 307

Vitamin D3 is absorbed PASSIVELY in the ileum, but this is not very efficient.

Answer 308

There is no difference. It is the same molecule.

Answer 309

In the liver, Vit D3 is HYDROXYLATED to form 25-OH D3 via 25-HYDROXYLASE (a cytochrome p450 enzyme).

Answer 310

25-OH D3 is secreted into blood bound to DBP. *This corresponds to the largest pool of 25-OH D3 in body.

Answer 311

Low 25-OH D3 in the blood is the key sign of Vit D deficiency.

Answer 312

When CALCIUM levels are low in the body, 25-OH D3 will be converted into an active molecule.

Answer 313

False. | High gradient of blood to intracellular Ca2+ is essential.

Answer 314

Low blood Ca2+ is sensed by the PARATHYROID GLAND.

Answer 315

When the parathyroid gland senses low blood Ca2+, it releases PTH (parathyroid hormone). PTH promotes uptake of 25-OH D3/ DBP complex into the kidney.

Answer 316

In the kidney, 1-hydroxylase converts inactive 25-OH D3 into active 1,25-(OH)2 D3.

Answer 317

The active form of Vitamin D3 (1,25-(OH)2 D3) is known as CALCITRIOL.

Answer 318

1. Genomic | 2. Non-genomic

Answer 319

- Vit D receptor (VDR) = nuclear hormone receptor - Transcription factor that promotes calcium binding protein synthesis - Calcium-binding proteins are activated by Vitamin K dependent post-translational modifications (γ-carboxylation)

Answer 320

- Binds cell surface receptors, like MARRS (membrane associated rapid response steroid-binding protein) - Activates intracellular signalling cascades - Very fast, no dependence on Vit K

Answer 321

1. VDR is activated and turns on the expression of genes coding for calcium binding proteins (require Vitamin K dependent γ-carboxylation to become fully functional) 2. Membrane transporters are activated (e.g., MARRS)

Answer 322

1. Elevated calcitriol and PTH work together to stimulate resorption of Ca2+ and Phorphorus from bone 2. Calcitriol causes an increase in the expression of RANK ligand (RANKL), a cytokine 3. RANKL activates osteoclasts to increase their activity 4. Osteoclasts secrete factors that degrade the bone matrix to release Ca2+ and P into the blood (high calcitriol (and pth) --> high RANKL --> high osteoclast activity)

Answer 323

1. Primary function is to increase absorption and reabsorption of Ca2+ 2. Calcitriol turns on the expression of genes coding calcium binding proteins

Answer 324

1. Absorption (small intestine) 2. Reabsorption (kidney) 3. Resorption (bone)

Answer 325

- Minerals need transporters to be absorbed by intestinal cells and enter into portal circulation - Proper absorption of Ca2+ depends on the expression of Ca2+ binding proteins in enterocytes

Answer 326

- Small molecules like Ca2+ circulate in blood and eventually reach the kidney, where they pass through the filter and can end up in the urine (unless reabsorbed) - Reabsorption removes the molecules from the filtrate and gets them back into the blood

Answer 327

- Dissolving bone structure to release Ca2+ into the blood (Osteoclasts resorb bone, osteoblasts build bone) - Balance between break-down and synthesis allows for bone maintenance, remodeling and repair

Answer 328

Serves to INCREASE blood calcium (1st response): - Promotes the production of calcitriol in kidney by activating 1-hydroxylase enyzme - Stimulates resorption of bone by activating osteoclasts - Maximizes tubular reabsorption of calcium in kidney - No direct effect on small intestinal absorption

Answer 329

Serves to INCREASE blood calcium: - Stimulates Ca2+ resorption from bone - Helps to increase absorption of Ca2+ from intestine - Maximizes tubular reabsorption of Ca2+ in kidney

Answer 330

Secreted by parafollicular cells in the thyroid Serves to DECREASE blood Ca2+ (e.g. in response to Ca2+ rebound): - Suppresses tubular reabsorption of Ca2+ in kidney - Inhibits bone resorption and facilitates remineralization

Answer 331

The composition of normal bone is a mixture of SOLID (outer) and SPONGY (inner) parts.

Answer 332

Solid part is 60% mineral (Ca2+, P) and 40% organic (collagen)

Answer 333

False. | In babies, bones start as COLLAGEN and gradually become infused with MINERALS.

Answer 334

Vit D deficiency concerns only the SOLID part of bones, as it changes the ratio of mineral to collagen in the bone matrix.

Answer 335

Vit D deficiency in Infants = Rickets (poor mineralization) - Bones don’t mineralize properly and can’t support the body’s weight when they start walking (permanent and reversible only with surgery) - Was seen in Britain during the industrial revolution

Answer 336

Vit D deficiency in Adolescents to Adult = Osteomalacia –-Bones become demineralized (can be reversed with supplementation) - Bone fractures can occur more easily

Answer 337

Vit D deficiency in Middle-Aged to Elderly = Osteoporosis - Normal part of aging (loss of both mineral and organic parts of bone) - Diagnosed with bone density scans - Difficult to reverse due to erosion of bone (holes in bone form)

Answer 338

UV treatment and cod oil.

Answer 339

Osteoporosis --> Bone loss associated with aging

Answer 340

False. Men have higher peak bone mass between 20-30 yrs and LOWER bone loss

Answer 341

Treatments include supplementation or drugs that affect bone formation/ resorption.

Answer 342

Menopause.

Answer 343

The RDA for Vit D intake for adults is 600 IU (international units). 1μg Vit D = 40 IU…so this means 15 μg of Vit D / day.

Answer 344

In 2010, the RDA was 200 IU. Health Canada tripled the RDA based on overwhelming scientific evidence (Used input from research, stakeholders, and scientists) Statscan found that a lot of canadians were deficient.

Answer 345

False. Production of Vit D3 is limited by amounts of 7-D present in the skin – Sunglight also produces the inactive lumisterol and tachysterol metabolites with prolonged sun exposure, which have no bioactivity

Answer 346

Very high dietary levels of Vitamin D can cause HYPERCALCEMIA, leading to a possible calcification of soft tissues.

Answer 347

They claim it supports a healthy immune system and bone health

Answer 348

Vitamin K is most important for bone FORMATION and blood COAGULATION.

Answer 349

Vitamin K is found in leafy greens as PHYLLOQUINONE, and made by gut bacteria in the form of MENAQUINONE.

Answer 350

- There is little Vit K in mother’s milk and babies aren’t eating leafy plants yet - Babies also haven’t developed their colonic (gut) bacteria, so no menaquinone - Babies given Vit K via a heel prick at birth

Answer 351

False. | Deficiency is very rare in adults due to bacterial production

Answer 352

Phylloquinone requires no digestion - Incorporated into micelles and absorbed in the small intestine - Absorbed via NPC1L1 apical transporter (also involved in cholesterol absorption)

Answer 353

Menaquinones produced by bacteria in the large intestine | – Passive absorption

Answer 354

Vit K can be stored in cell membranes in lungs, kidneys, adrenal glands, bone, etc.

Answer 355

Phylloquinone in PLANTS (Vit K1): Saturated side chain Menaquinone by BACTERIA (Vit K2): Unsaturated side chain

Answer 356

γ-CARBOXYLATION is the post-translation modification that Vit K is responsible/ essential for.

Answer 357

WARFARIN= (anti-coagulant drug) rat poison that functions by inhibiting epoxide reductase, keeps vitamin k in inactive form and prevents the pathway from taking place.

Answer 358

Gla residues on blood clotting proteins bind Ca2+. Ca2+ allows Gla-containing proteins to bind to phospholipids on membranes of blood platelets and endothelial cells.

Answer 359

1. Newborn infants (injected with phylloquinone at birth) - Little Vit K in breast milk - Vit K can’t cross the placenta for delivery to the developing fetus - Gut bacteria population not established 2. People who take antibiotics chronically - Antibiotics destroy the gut bacterial community (can no longer produce menoquinone) 3. People with malabsorptive illnesses (IBD, Crohn’s, pancreatitis)

Answer 360

1. Impaired blood clotting - Possible hemorrhagic syndrome (mostly seen in newborns) 2. Impaired activation of calcium binding proteins - Accelerate development of osteoporosis (mostly seen in elderly adults)

Answer 361

Helps to prevent osteoporosis and develop strong bones.

Answer 362

Calcium represents 40% of the body's mineral mass. *1,000 – 1,400 mg in human body

Answer 363

99% --> Bones and teeth contain | 1% --> critically important for signalling pathways

Answer 364

Parathyroid hormones.

Answer 365

Predominantly obtained from dairy products, but also high in sardines, salmon, and some green leafy vegetables *Present in these foods as an insoluble salt – Stomach acid creates soluble Ca2+

Answer 366

Small intestine.

Answer 367

Primary uptake: Saturable, carrier-mediated, active transport • Absorption regulated by calcitriol; Most calcium absorbed this way Secondary pathway uptake: Diffusion via paracellular route is

Answer 368

~40% bound to albumin ~10% found complexed with sulfate, phosphate, etc ~50% found in free (ionized) form

Answer 369

BONE Calcium (99%) - Minerals (calcium, phosphorus, fluoride, magnesium, potassium, etc) make up hydroxyapatite (a crystal like structure) (This is ~60% of solid bone mass)

Answer 370

INTRA- and EXTRACELLULAR Calcium (1%) Ionized calcium is active and used for: - Blood clotting (formation of “Gla” residues on coagulation proteins) - Skeletal muscle contraction (release of calcium stores) - Nerve potential (acting through ion channels) Intracellular signalling pathways (e.g., Ca2+ activates PLA2, which cleaves arachidonic acid from phospholipids to produce eicosanoids)

Answer 371

Bone is sacrificed in this case.

Answer 372

- Most is stored in mitochondria and ER - Released from stores in response to an extracellular signal (e.g. receptor binding) to ultimately promote an intracellular response (e.g., gene expression, neurotransmission, etc.) (leads to depolarization of the cell, and very rapid changes)

Answer 373

-Maintained at a very constant level; ~10,000x the concentration of intracellular calcium*** (when something happens within the cell that needs the response of calcium, there is a very favourable gradient that allows calcium to rush into the cell and come into effect) – Nearly identical to the concentration of phosphorus (detected by parathyroid hormone)

Answer 374

- The majority (around 99%) of the calcium in the body is in the bone and teeth - In bone, 99% is in mineral phase (hydroxyapatite), and 1% is in a pool that can exchange with extracellular calcium

Answer 375

↑ UL in children ↓ UL in adults (51-70 yrs) ↓ UL in >70yrs to prevent developing kidney stones

Answer 376

↑ UL in children (help mineralization and formation of bones) ↓ UL in adults (51-70 yrs) (due to kidney stones) ↓ UL in >70yrs to prevent developing kidney stones

Answer 377

``` Caffeine ↓ Some fibres ↓ Magnesium & Zinc ↓ PTH (Vit D) ↑ Pregnancy & lactation ↑ (this is why RDA for calcium remains the same during pregnancy) ```

Answer 378

*Profoundly affects bone and muscle 1. Bone • Inadequate mineralization in bone – Rickets in children (commonly associated with Vit D deficiency) – Osteomalacia in adults (and increases risk of developing Osteoporosis) 2. Muscle • Tetany – A condition characterized by involuntary muscle contractions 3. Evidence for association with hypertension 4. Evidence for association with colon cancer (current research supports association in high risk populations)

Answer 379

1. Constipation, bloating, and/or gas 2. Hypercalcemia (calcification of soft tissues) – Kidney stones

Answer 380

Phosphorus.

Answer 381

Phospphorys is widely distributed in foods.

Answer 382

Phosphorus is found in animal products as PHOSPHORUS and in grains as PHYTIC ACID.

Answer 383

Most phosphorus is absorbed in the small intestine in its ionic form - Passive diffusion (primary method) - Saturable, carrier-mediated, active transport (NaPi cotransporter) (could also be with ATP active transport) 50-70% of the phosphorus in foods is absorbed.

Answer 384

Absorption inhibited by magnesium, aluminum, & calcium (these are called phosphate binders).

Answer 385

Absorption inhibited by magnesium, aluminum, & calcium (these are called phosphate binders).

Answer 386

Phosphorus is primarily transported in the blood as ORGANIC PHOSPHATE (it is incorporated into PHOSPHOLIPIDS).

Answer 387

Phosphorus is found largely in bone (HYDROXYAPATITE), but also in molecules key for metabolism like ATP, DNA, RNA, cAMP, etc.

Answer 388

Phosphorus plays a key role in protein PHOSPHORYLATION, a common PTM in proteins.

Answer 389

No. | Fluoride is present in the body in trace amounts.

Answer 390

Community water fluoridated (with ~1 ppm or ~1mg/L) for the past 60 years

Answer 391

Absorption in stomach by passive diffusion (nearly 100% efficiency)

Answer 392

Transported in the body as ionic fluoride or bound to plasma proteins.

Answer 393

Increases resistance of enamel to acid demineralization by forming fluoroapatite (protective layer)

Answer 394

Increased incidence of tooth decay

Answer 395

Fluorosis (mottling of the teeth) -Tolerable upper limit in adults is 10mg/day

Answer 396

Fluorosis (mottling of the teeth) -Tolerable upper limit in adults is 10mg/day

Answer 397

Group II micronutrients are involved in REDOX reactions.

Answer 398

- Involves the transfer of electrons between two substrates (donor and acceptor) - Many biochemical reactions are essentially electron transfers

Answer 399

• The primary electron carriers in the body are NADH and FADH2 They are important for the creation of ATP.

Answer 400

``` Glycolysis Lactic Acid Production Pyruvate Dehydrogenation Kreb’s Cycle Gluconeogenesis β-oxidation ```

Answer 401

The primary electron carriers in the body are NADH (niacin) and FADH2 (riboflavin) They are important for the creation of ATP.

Answer 402

``` Glycolysis Lactic Acid Production Pyruvate Dehydrogenation Kreb’s Cycle Gluconeogenesis β-oxidation ```

Answer 403

Reactive Oxygen Species (ROS). -ROS produced as a by product of the ETC when proper electron flow fails (~1% “leakage") - Occurs in a O2 rich environment, where oxygen can react with electrons (causes oxygen radicals with free electrons that are very reactive)

Answer 404

Mutations in SOD cause Lou Gehrig's.

Answer 405

H2O2 is converted to H2O by GLUTATHIONE PEROXIDASE and CATALASE (selenium dependent enzymes).

Answer 406

T3 and T4 production

Answer 407

H2O2. Glutathione perosidase converts H2O2 to 2 H2O, but if H2O2 reacts with a free electron, there is a Fenton reaction, creating a hydroxyl radical.

Answer 408

H2O2. Glutathione perosidase converts H2O2 to 2 H2O, but if H2O2 reacts with a free electron, there is a Fenton reaction, creating a hydroxyl radical.

Answer 409

Mixed tacopherol antioxidant support

Answer 410

Vitamin E is a general term that describes 8 structurally-related compounds known as VITAMERS.

Answer 411

1. 4 tocopherols - Have saturated side chains with 16 carbons 2. 4 tocotrienols - Have unsaturated side chains with 16 carbons Vitamers in both classes ( α , β , γ , δ) *Although they are all similar, the differences are big enough at the molecular level that they have different transport proteins (especially tocopherol)

Answer 412

Only α-tocopherol has significant activity in the body

Answer 413

There is no inter conversion of vitamers in animals Ex., β-tocotrienol cannot be converted into α-tocopherol

Answer 414

Tocopherols

Answer 415

The tocopherol nomenclature is used to describe the # and position of RING METHYL (CH3) groups.

Answer 416

The HYDROXYL group is the antioxidant site of vitamers.

Answer 417

α isoform has the most methylated ring.

Answer 418

Transport mediated uptake in the small intestine (e.g., NPC1L1)

Answer 419

The “R” and “S” of vitamers refers to CHIRAL CARBON configuration of methyl groups on side chain.

Answer 420

Natural α-tocopherol is RRR - Fits into the binding pocket of the Tocopherol Transfer Protein (TTP) * It is the only one that fits into TTP properly

Answer 421

Tocotrienols.

Answer 422

Transport mediated uptake in the small intestine (e.g., NPC1L1)

Answer 423

Tocotrienols are only not converted to α-tocopherol or able to fit in the TTP binding pocket.

Answer 424

- Food sources: nuts, seeds, vegetable oils, avocado | - Mostly obtained from plants because stored in adipose tissue in animals (and we don’t normally eat the fat).

Answer 425

Yes. (Sensitive to food preparation & storage (e.g. roasting nuts ↓ Vit E levels)

Answer 426

True. Adults (15 mg = 22.4 IU) of α-tocopherol per day - The RDA is increased for pregnant women compared to age matched non pregnant women (due to oxidative damage that can occur to the fetus)

Answer 427

Estimated with tests to examine the hemolysis (breakdown) of red blood cells in the presence of dilute H2O2 (put RBC in dilute H2O2 and see what happens; lack of vitamin E = hemolysis) - (>20% RBC hemolysis means there is a Vit E deficiency)

Answer 428

UL = 1,000 mg / day (above this amount will cause increased bleeding) - However, gastrointestinal problems can be seen at lower levels than the UL *Note: UL changes from person to person, some people have GI problems at 600mg or lower

Answer 429

1. Pre-mature infants (kept in oxygen rich incubators, which increases oxidative stress) 2. People with fat malabsorption disorders or gallbladders removed 3. People with genetic defects in lipoproteins or TTP (need to be monitored as they have problems transporting vitamin e across the body)

Answer 430

1. Requires bile acids for emulsification & incorporation into micelles 2. Absorbed in small intestine by transporters (e.g., NPC1L1) 3. Packaged into chylomicrons 4. Chylomicron remnants, containing Vit E, are taken up by the liver 5. Liver makes TTP, which is needed to get α tocopherol packaged into VLDL (Other vitamers can help a bit with anti-oxidant activity in the liver only, but are quickly degraded) 6. No specific “storage” organ for Vit E, but most of it goes into lipid droplets in adipose tissue

Answer 431

Lines of Defense: 1. GSH peroxidase 2. Vitamin E 3. FA peroxidase

Answer 432

Super Antioxidant support

Answer 433

Plants incorporate selenium from the soil into methionine and cysteine AAs instead of sulfur Therefore, selenium content in food is determined by selenium levels in the soil *Note: selenocysteine makes certain proteins function, selenomethionine makes them not functional.

Answer 434

SelenoAA are absorbed in the small intestine by amino acid transporters and travel freely in the blood

Answer 435

The body uses selenocysteine –~30 specific selenocysteine containing proteins in body that are involved in thyroid hormone metabolism, DNA synthesis and protection from oxidative damage

Answer 436

- China and Africa (low Se in soil) - Keshan disease (cardiomyopathy from cell damage by free radicals)

Answer 437

Selenosis --> chronic consumption of lots of brazil nuts which are rich in selenium can lead to hair and nail loss (most common symptoms)

Answer 438

1. Glutathione peroxidase = 1st line of defence against lipid peroxidation 2. Fatty acid peroxidase = 3rd line of defence against lipid peroxidation

Answer 439

Both selenoproteins use GLUTATHIONE (GSH) as a substrate, which helps to protect cells against oxidative damage (it acts as the reducing agent).

Answer 440

The structure of glutathione is crucial as GLUTAMATE and CYSTEINE linked through a gamma-carbon. This gamma peptide bond is resistant to cellular PROTEASES. *Note: glutathione itself does not have selenium in its structure.

Answer 441

Selenium gets incorporated into the enzymes, not into the glutathione itself. It is however within the peroxidase enzyme. Glutathione is a SINGLE electron donor (1 electron per glutathione) and it is a reducing agent. Glutathione will donate an electron from its thiol group, but it keeps its structure thanks to the bond between cysteine and glutamate - glutamate is attached to cysteine via its side chain (gamma carbon) this gamma-peptide bond gives stability --> resistant to cellular proteases it allows glutathione to function as a good reducing agent within the cell

Answer 442

2 GSH. | GSH is oxidized and reacts with another GSH to form GSSG.

Answer 443

``` High cellular levels of GSSG indicative of high oxidative stress. ```

Answer 444

High cellular levels of GSSG indicative of high oxidative stress.

Answer 445

False. | Oral GSH supplements not very effective because they are poorly absorbed.

Answer 446

The pentose phosphate pathway (HEXOSE MONOPHOSPHATE SHUNT) regenerates NADPH (which requires niacin).

Answer 447

Jamison claims vitamin c has antioxidant support. | A better description would be support the immune system.

Answer 448

Vitamin C is ASCORBIC acid; at physiological pH is it known as ASCORBATE.

Answer 449

The L isomer is biologically active in humans.

Answer 450

This is because we lack the specific enzyme gulonolactone oxidase. Glucose (or galactose) --> gulonolactone --(gulonolactone oxidase) --> ascorbic acid

Answer 451

Fruits and vegetables.

Answer 452

Vitamin C doesn’t require digestion prior to absorption.

Answer 453

Uptake via sodium dependent vitamin C (SVCT) 1 and 2 transporters in the small intestine (feedback mechanism exists) - 70 90% dietary Vit C is absorbed - There appears to be a maximum amount of Vit C that can be absorbed (this is what feedback mechanism means)

Answer 454

Found in circulation primarily in “free form” (i.e., not bound to a protein)

Answer 455

Found in circulation primarily in “free form” (i.e., not bound to a protein)

Answer 456

Reduced: Ascorbic acid Oxidized: Dehydroascorbic acid *Foods contain mostly ascorbic acid, but can have small amounts of the oxidized form (dehydroascorbic acid).

Answer 457

Vit C concentrations are high in WHITE blood cells, as well as in many tissues.

Answer 458

Collagen synthesis.

Answer 459

True. | "2 electron donor"

Answer 460

Proline-OH.

Answer 461

Electron donated from Vit C is used to form proline OH.

Answer 462

Collagen is what gives tissues their structure.

Answer 463

Each ascorbic acid reactivates 2 prolyl hydroxylases.

Answer 464

This evidence suggests that Vitamin C has a role in oxidant defense.

Answer 465

This evidence suggests that Vitamin C has a role in oxidant defense.

Answer 466

RDA goal: to maximize tissue concentrations and minimize urinary excretion.

Answer 467

RDA is increased in pregnant and lactating women to support mother and infant. *Collagen plays a huge role in the development of the fetus --> bone (cartilage), tissue, organs

Answer 468

Above this amount increases risk for digestive problems (diarrhea) and kidney stones.

Answer 469

1. Scurvy (plasma Vit C levels < 0.2 mg/ dL (If you consume 10 mg Vit C per day, signs of scurvy develop in 1 month) 2. Increased risk of hemorrhages (skin, follicles, gums) 3. Increased hair loss, loose teeth 4. Swollen joints, poor wound healing - due to problems producing hydroxyproline (i.e.

Answer 470

The gums. | Since they have such a high turnover rate, if there was a problem making collagen, that's where we would see it first.

Answer 471

limey's = term to describe british sailors - early physicians realized that british soldiers that didn't have any citrus fruit had scurvy, and to prevent that they started bringing limes with them

Answer 472

• False. -Meta analyses suggest that Vit C does not prevent colds (except in people performing intense physical activity (e.g. marathon running)) - Some evidence suggesting Vit C shortens the duration of a cold

Answer 473

Vitamin E: scavenges PUFA peroxy radicals within the cell.

Answer 474

Selenium: Essential for the proper functioning of selenoproteins. – Glutathione Peroxidase (reduces hydroxyl radicals by converting H 2 O 2 into water) – FA Peroxidase (converts PUFA hydroperoxides into PUFA alcohols)

Answer 475

Vitamin C: major blood reducing agent, but it’s role in oxidant defence remains debatable. However, Vit C is critical for the production of hydroxylated prolines.

Answer 476

Sulfur AA (cysteine): is necessary for the synthesis of glutathione (GSH).

Answer 477

Niacin: is required to make NADPH (which is needed to regenerate GSH by glutathione reductase)

Answer 478

Riboflavin: also required by glutathione reductase as a coenzyme

Answer 479

Zn2+ and Cu+: are enzyme cofactors that donate electrons to convert superoxide into H2O2.

Answer 480

Free Fe2+ in the cell in the presence of H2O2 increases risk for making hydroxyl radicals.

Answer 481

Free Fe2+ in the cell in the presence of H2O2 increases risk for making hydroxyl radicals.

Answer 482

Group III: Micronutrients that act as enzyme cofactors ex. Thiamin, Niacin, Riboflavin, Vit B6, Folate, Vit B12, Biotin, Pantothenic acid

Answer 483

Converts carbs, proteins, fats to energy. *It plays an important role in biochemical pathways used to produce energy.

Answer 484

Niacin is also called Vitamin B3.

Answer 485

Discovered through the condition pellagra in humans and a similar condition, called black tongue, in dogs -Niacin was considered the “anti black tongue” factor - High incidence in areas where corn is the main dietary staple (because niacin is attached to indigestible carbohydrates in corn, therefore it is poorly absorbed) * pellagra began when explorers came to america and started eating corn; you can't digest the niacin in corn well, and so the indigenous people had a special way of preparing it to "release" the niacin, however the explorers did not do that.

Answer 486

Most fish, meats, breads and cereals, coffee and tea. *In coffee, trigonelline is converted to niacin by heat (ie ., coffee bean roasting)

Answer 487

1. Nicotinamide 2. Nicotinamide adenine dinucleotide (NAD) 3. Nicotinamide adenine dinucleotide phosphate (NADP)

Answer 488

In plant foods, Vitamin B3 is predominantly found as NICOTINIC ACID, which is considered a provitamin.

Answer 489

No. Only about 1/60 th of Trp is converted into niacin. *Note: Although the conversion is very small it is still taken into account by government when creating RDA values.