biochem exam 4/8/24 Flashcards

1
Q

the more active form of glutamine synthetase is the

  1. adenylylated form of the enzyme
  2. de-adenylylated form of the enzyme
A
  1. de-adenylylated form of the enzyme
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2
Q

PII is the factor that binds to adenylyl transferase (AT). If PII is uridylylated

  1. AT preferentially catalyzes the adenylation of glutamine synthetase (GS)
  2. AT preferentially catalyzes the de-adenylation of GS
A
  1. AT preferentially catalyzes the de-adenylation of GS
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3
Q

An elevated glutamine concentration leads to…

A. An increase in the [PII + UMP]
B. A decrease in the [PII + UMP]
C. The de-adenylation of glutamine synthetase

A

B. A decrease in the [PII + UMP]

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4
Q

When there is a sufficient amount (or more) of gln in a cell, which of the following is true about glutamine synthetase and the associated regulatory enzyme

  1. AT-PII will be uridylylated, GS will not be adenylylated and GS will be active
  2. AT-PII will be uridylylated, GS will be adenylylated and GS will be inactive
  3. AT-PII will not be uridylylated, GS will be adenylylated and GS will be inactive
  4. AT-PII will not be uridylylated, GS will not be adenylylated and GS will be active
A
  1. AT-PII will not be uridylylated, GS will be adenylylated and GS will be inactive
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5
Q

heme is derived from ____ and is broken down to form ____

  1. arginine, creatine
  2. glycine, creatine
  3. glycine, bilirubin
  4. blirubin, creatine
A
  1. glycine, bilirubin
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6
Q

Which of the following statements is incorrect?

A. GABA is derived from glutamate
B. Histamine→histidine
C. Serotonin→tryptophan
D. Dopamine→tryptophan
E. Epinephrine→tyrosine

A

D. Dopamine→tryptophan

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7
Q

therapies for Parkinson’s disease include

  1. block formation of L-Dopa
  2. administer L-dopa to the patient
  3. accelerate dopamine breakdown
  4. administer an MAO inhibitor
A
  1. administer L-dopa to the patient
  2. administer an MAO inhibitor
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8
Q

which of the following reactions is part of the normal nucleotide synthesis

  1. AMP to dAMP
  2. GDP to dGDP
  3. TDP to dTDP
  4. UTP to dUTP
  5. CMP to CDP
A
  1. GDP to dGDP
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9
Q

Folate and/or vitamin B12 is/are required for the synthesis of…

A. dAMP
B. dCMP
C. dGMP
D. dTMP
E. dUMP

A

D. dTMP

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10
Q

which statement is false

  1. gout involves uric acid crystals in joints
  2. purine catabolism leads to uric acid formation
  3. allopurinol inhibits uric acid breakdown
  4. allopurinol inhibits xanthine oxidase
A
  1. allopurinol inhibits uric acid breakdown
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11
Q

which of the following inhibits the reduction of NDPs to dNDPs

  1. allopurinol indomethacin
  2. azaserin, acivicin
  3. aminopterin, methotrexate
  4. gemcitabine
A
  1. gemcitabine
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12
Q

which of the following are Gln analogs that interfere with nucleotide synthase

  1. allopurinol indomethacin
  2. azaserin, acivicin
  3. aminopterin, methotrexate
  4. gemcitabine
A
  1. azaserin, acivicin
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13
Q

aminopterin, methotrexate, and fluorouracil reduce the synthesis of

  1. glutamate
  2. glutamine
  3. cAMP
  4. dAMP
  5. dTMP
A
  1. dTMP
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14
Q

Sources of Nitrogen

A

Ammonia is toxic to mammalian cells and must be immediately used up (assimilated) or converted to urea and removed (Ch 18)

Soluble, biologically useful nitrogen-containing molecules are generally scarce, so organisms are conservative in their use

Ammonia is assimilated into glutamine (major) and glutamate (minor) in mammalian cells.
Glutamine and glutamate are the nitrogen sources for the cellular synthesis of other amino acids and other nitrogenous compounds.

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15
Q

Assimilation of Ammonia into Glutamine (Major Pathway)

A

Glutamate + glutamine synthetase = acyl-phosphate intermediate

Glutamine is the source of amino groups for most other nitrogenous compounds.

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16
Q

Major Source of Glutamate

A

Breakdown of excess dietary amino acids by transamination reactions yields high levels of cellular glutamate, shortly after the meal is consumed.

Glutamate is the source of amino groups for most other amino acids.

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17
Q

Assimilation of Ammonia into Glutamate (Minor Pathway)

A

Km for NH4+ = 1 mM rendering glutamate synthesis only possible when [NH4+] is abnormally high (hyperammonemia).

In cells, both Glutamine and Glutamate are kept at concentrations higher than other amino acids

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18
Q

Allosteric Regulation of Glutamine Synthetase

A

Each molecule alone partially inhibits the enzyme…

6 of these are derived from glutamine

If all products are present at sufficiently high levels, the enzyme is essentially turned off.

Don’t need it, don’t make it.

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19
Q

Covalent Regulation of Glutamine Synthetase

A

GS + AMP = OFF
GS = ON
PII + UMP + AT = GS ON (via deadenylation)
PII + AT = GS + AMP = OFF (via adenylation)

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20
Q

Simplified: Covalent Regulation of Glutamine Synthetase

A

high ATP or high alpha ketoglutarate, low Gln
- AT-PII uridylyated - yes
- GS adenylylated - no
- GS active - yes

low ATP or low alpha-ketoglutarate or high Gln
- AT-PII uridylyated - no
- GS adenylylated - yes
- GS active - no

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21
Q

Essential and Non-Essential Amino Acids

A

Essential Amino Acids:
- Amino acids that cannot be synthesized (made) by an organism and must be a component of the diet.

Non-Essential Amino Acids:
- Amino acids that can be synthesized by an organism and are not required to be a component of the diet.

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22
Q

Amino Acid Synthesis

A

Synthesized from 6 common precursors!
- Sometimes more than one way…

We’ve seen some of these already:
Phenylalanine→Tyrosine (PKU) Pyruvate→Alanine (Muscle) Oxaloacetate→Aspartate (Urea Cycle) α-KG → Glutamate (Transamination) Glutamate→Glutamine (Above)
Connections:
Serine→Glycine uses THF (remember?!) Methionine cycle involves SAM, B12, Folate (B9)!

Glycolysis, PPP, CAC, AA Catabolism, etc.

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23
Q

Porphyrins (Heme)

A

Heme isn’t just for hemoglobin:
Myoglobin, catalase, peroxidase, P450 liver cytochromes

Deficiency in the enzymes in this pathway cause a build-up of toxic porphyrins→ Porphyria

“Mad” King George III
Genetic, can be triggered by meds Different porphyrias, different symptoms Neurological, skin, photosensitivity

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24
Q

heme breakdown

A

to bilirubin etc.

a stronger antioxidant, but an elevated level in blood may indicate liver disease

heme breakdown color: black/blue/purple

biliverdin breakdown color:
green

bilirubin breakdown in blood:
yellow

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25
creatine from Gly, Arg, Met
a ready source of phosphoryl groups for quick synthesis of ATP (phosphocreatine s later replenished by phosphoryl transfer from ATP) ADP + PCr = ATP + Cr delta G = -12.5kJ/mol
26
Neurotransmitters: Derived from Amino Acids
dopamine, norepinephrine, epinephrine gamma-aminobutyric acid (butyrate) - GABA serotonin histamine nitric oxide (NO)
27
From tyrosine:
dopamine, norepinephrine, epinephrine catecholamines tyrosine - deficiency of this coenzyme results in deficiency of catecholamines as well as PKU dopamine - too little: associated with Parkinson's norepinephrine regulates blood pressure epinephrine fight or flight
28
Therapy for Parkinson’s Disease
raise dopamine levels (L-dopa) maintain dopamine levels by inhibiting monoamine oxidase (MAO inhibitors, such as selegiline) - xadago (safinamide) L-dopa is the precursor to dopamine L-dopa crosses the BBB, dopamine cannot can be metabolized in the periphery challenge: must get L-dopa to the brain without being metabolized if you do not beat this challenge 1. side effects 2. reduced availability of DOPA in the brain solution - co-administer with a DOPA carboxylase inhibitor so that the drug isn't metabolized to DOPA in the periphery, and therefore more DOPA gets to the brain
29
from glutamate
GABA 1. astrocytes control the biosynthesis and turnover of glutamate and GABA 2. there are other ways to treat epilepsy - not just through GABA 3. can be co-released with glycine (also inhibitory; AA) lack associated with epileptic seizures. treatment: administer GABA analogs or inhibitor breakdown
30
from tryptophan
serotonin - suppresses appetite - induces fatigue - makes you mellow brainstem control of respiration serotonin syndrome: DDI Trp is also a precursor of melatonin which is involved in the control of circadian rhythms tetrahydrobiopterin - deficiency of this coenzyme results in deficiency of serotonin and PKU Monoamine oxidase - maintains serotonin levels
31
from histidine
histamine released in allergic response and stimulates acid secretion in the stomach this structural analog interferes with the action of histamines (an H2 receptor antagonist used to treat gastric reflux)
32
from arginine
nitric oxide involved in neurotransmission, blood clotting, control of blood pressure gas activates GC to cGMP for vasodilation
33
De Novo (From Scratch) Nucleotide Synthesis
NMPs are synthesized "on phosphorizes" not by adding free bases to ribose Ribose + P to P-ribose to NMP not by attaching a pre-formed base to P-Ribose basically - start with the P-ribose and synthesize the rest of the P-Ribose
34
purine nucleotide synthesis
35
Purine Nucleotide Synthesis: Salvage Pathway
Some tissues can’t De novo, so when RNA/DNA degenerates, bases and nucleosides can be recovered, and recycled back into nucleotides. adenine + PRPP to adenylyase PPi enzyme: adenine phosphoribosyltransferase hypoxanthine + PRPP to inosinate + PPi guanine + PRPP to guanlyate + PPi enzyme: hypoxanthine-guanine...
36
Nucleotide Synthesis
general scheme: nucleotide synthesis start mono add phosphates Ribose → deoxyribose via reduction
37
folate, vtamine/coenzyme B12 & DNA synthesis
folate & B12 required for DNA synthesis
38
B12 and or folate deficiency
one serious consequence of B12 or folate deficiency as N5, N10-Me THF defc. dTMP def. and reduced DNA synthesis
39
Nucleotide Degradation
purine nucleotides to urc acd to excretion pyrimidine nucleotides to NH4 to ureaa to excretion
40
Excessive Purine Catabolism
Following excessive purine consumption or synthesis If this happens→overproduction of uric acid→ high [uric acid] in the blood and tissues... Then urate crystals (the salt of uric acid) get deposited in the joints which become inflamed, painful, and arthritic. Additional deposits found in the kidneys * The above are signs of Gout. Cause unknown, maybe genetic? 90% of affected individuals are men > 40 years old * Effects ~ 1 million Americans * Joint of big toe affected ~ 50% of cases
41
Gout
control of Gout: Limit intake of foods rich in purines: meat (esp: liver), poultry, seafood Avoid: alcohol, fructose-sweetened drinks, and obesity (these increase risk) Vitamin C, dairy products, and coffee (not tea) may reduce risk * Treatment for Gout Allopurinol – an irreversible inhibitor of xanthine oxidase – the enzyme that converts purines to uric acid Allopurinol therapy results in the accumulation of xanthine and hypoxanthine (instead of uric acid/urate), which are soluble (uric acid is not) Other drugs you might see: Probenecid, Febuxostat Treat pain/inflammation with NSAIDs, steroids, colchicine
42
Cancer
cancer cells are growing much more rapidly than most normal tissues, and have a great need for nucleotides, precursors of DNA & RNA a growing array of anti-cancer drugs interfere with nucleotide biosynthesis: - glutamine analogs - glutamine to source for nucleotides - inhibition of ribonucleotide reductase - ribose to deoxyribose - thymidylate synthesis blockers - need T's
43
Glutamine Analogs
Looks like glutamine, but isn’t. Interferes with enzymatic reactions involving glutamine and the formation of nucleotides Gln is a nitrogen donor in many nucleotide synthesis rxns mechanisms unclear: competitive or suicide inhibition research only
44
Ribonucleotide Reductase Inhibition
gemcitabine seems to do that
45
Blocking dTMP Synthesis
use fluorouracil on dUMP
46
Resting muscle derives most of its energy from...?
A. Muscle glycogen B. Fatty acids C. Blood glucose D. Phosphocreatine
47
the cori cycle involves the transport of ____ from muscle tissue to the liver and of _____ from the liver to muscle 1. glucose, glutamine 2. alanine, glucose 3. lactose, glucose 4. glucose, lactate 5. lactate, glucose
5. lactate, glucose
48
Which of the following carries out only aerobic metabolism and therefore must have access to oxygen (O2)? A. Liver B. Adipose tissue C. Skeletal muscle D. Cardiac muscle E. Brain
49
which of the following normally uses only glucose as a source of energy 1. the liver 2. adipose tissue 3. skeletal muscle 4. cardiac muscle 5. the brain
5. the brain
50
which of the following (types of) hormones is relatively fast-acting 1. catecholamines 2. vitamin D 3. Eicosanoids 4. retinoids 5. steroids
1. catecholamines 3. Eicosanoids
51
an elevated level of insulin would lead to a(n) _____ in glucose synthesis in the liver increase decrease
decrease
52
an elevated level of glucagon would lead to a(n) in glycogen breakdown n the liver increase decrease
increase
53
An elevated level of cortisol would lead to a(n) ___ in fatty acid mobilization from adipose tissue. A. Increase B. Decrease
A. Increase
54
an elevated level of epinephrine would lead to a(n) ___ in glucose synthesis in the liver increase decrease
increase
55
an elevated level of epinephrine would lead to a(n) ___ in glucagon secretion increase decrease
increase
56
what effect will an elevated level of insulin have on (i) glycogen breakdown in the liver and muscle and on (ii) fatty acid synthesis in the liver 1. (i) promote (ii) promote 2. (i) promote (ii) inhibit 3. (i) inhibit (ii) promote 4. (i) inhibit (ii) inhibit
3. (i) inhibit (ii) promote
57
The TCA cycle is the central metabolic hub
AA carbon skeletons Electron extractor Building block and energy import/export
58
Subcellular locations of the major metabolic pathways
59
Specialized Functions of Tissues/Organs
liver - processes fats, carbohydrates, and proteins from det; synthesizes and distributes lipids, ketone bodies, and glucose for other tissues; converts excess nitrogen to urea brain - transports ions to maintain membrane potential; integrates inputs from body and surroundings; sends signals to other organs cardiac muscle - uses ATP generated aerobically to pump blood lymphatic system - carries lipids from the intestine to the liver adipose tissue - synthesizes stores and mobilizes triacylglycerols. Brown adipose tissue carriers out thermogenesis skeletal muscle - uses ATP generated aerobically or anaerobically to do mechanical work
60
The Liver
The central metabolic organ; it transforms and exports/imports molecules. Hepatocytes transform dietary nutrients into fuels and precursors required by other tissues. Flexible: can adjust enzyme levels to adjust to nutritional state Oxidative organ: detoxifies foreign organic compounds (Cytochrome P-450 and others) Regenerates!
61
carbohydrate metabolism (liver)
fates of glucose 6-phos 1. glucose (blood) 2. glycogen 3. glycolysis to CAC 4. Glyc. to AcCoA to anabolism 5. pentose phosphate pathway glucose to G-6-P - free glucose (blood) - liver glycogen (storage) - energy via glycolysis and CAC - acetyl-CoA - synthesis of larger molecules via glycolysis - NADPH & nucleic acid precursors via the PPP
62
Amino acid metabolism
fates of AA's 1. protein (liver) 2. protein (elsewhere) 3. nucleotides etc. 4. deamination A. urea B. Pyruvate - glucose, acetyl-CoA Amino acid users 1. protein synthesis in the liver 2. export to other tissues for protein 3. synthesis of nucleotide, hormones etc 4. deamination for: a. gluconeogenesis b. CAC to ATP c. lipid synthesis d. transformation into ammonia and urea
63
fatty acid metabolism
FA's are the primary fuel in the liver fates of FA's 1. liver lipids 2. acetyl-CoA to CAC a. CAC (energy) b. ketone bodies c. cholesterol etc 3. plasma lipoproteins 4. transport (free FA) fatty acid uses: 1. storage in lipids (tails) 2. Major oxidative fuel for the liver (beta-oxidation to acetyl CoA to CAC) 3. transformation into ketone bodies, transported to other places 4. formation of cholesterol 5. incorporated into lipoproteins, transported to other places 6. combine with serum albumin, and transport to other places as a source of energy
64
Adipose Tissue
fatty acids cycle between TAGs and FFAs 2/3 of adipose tissue is TAGs
65
Skeletal Muscle
The source of energy depends on the activity level 1. At rest: source of energy comes from fatty acids (from adipose tissue) and ketone bodies (from the liver) 2. Moderate activity level: source of energy comes from FAs, KBs, AND glucose 3. Heavy activity level: source of energy comes from all of the above AND muscle glycogen (transformed into lactate) AND phosphocreatine
66
Time course of fuel consumption
creatine phosphate anaerobic metabolism ATP
67
the Cori cycle
how muscles use and replenish glycogen with the assistance of the liver muscle: during heavy exercise, glycogen is broken down and anaerobic glycolysis leads to the formation of ATP and lactate liver: rapid respiration produces ATP, which is used to form glucose from lactate in the liver
68
Heart Muscle and Brain
heart muscle - completely aerobic - mitochondria abundant (~50% of cell volume) - fuel: FA's (main source), glucose, KB's phosphocreatine (minor source) - lack of O2 fatal brain - normally uses only glucose, but can use KB's - very active: accounts for 20% of O2 use when the body is at rest
69
types and classes of hormones
autocrine: acts on the same cells paracrine: acts on adjacent cells endocrine: acts on distant cells 1. Biosynthesis 2. Storage and Secretion 3. Transport 4. Binding 5. Relay and Amplification (cellular response) 6. Breakdown
70
Hormones
cell surface receptor - peptide or amine hormone binds to a receptor on the outside of the cell; acts through the receptor without entering the cell nuclease receptor - steroid or thyroid hormone enters the cell; hormone-receptor complex acts in the nucleus
71
Hormones
plasma membrane receptors; relatively fast-acting Peptide Hormones 3-200+ amino acids in length Pancreatic: insulin, glucagon, somatostatin – growth hormone inhibiting hormone – GHIH) Thyroid: calcitonin (calcium homeostasis and metabolism) All hypothalamic and pituitary hormones Catecholamine Hormones Tyrosine (precursor) → L-DOPA → Dopamine → Norepinephrine → Epinephrine (Chapter 22) Eicosanoid Hormones
72
Hormones
steroid hormones: cholesterol to progesterone to cortisol or aldosterone or testosterone Vitamin D calcium homeostasis and metabolism to 7-dehydrocholesterol + UV light to vitamin D3 to 25-hydroxycholecaliiferol to 1,25-dihydroxycholecalciferol Retinoid Hormones Embryonic Development, Vision beta carotene to vitamin A1 (retinol) to retinoic acid
73
Hormones
hormone regulation of fuel metabolism peptides - insulin (high blood glucose) - glucagon (low blood glucose) catecholamine - epinephrine (stress; fast acting) steroid - cortisol (stress; slow acting) thyroid hormones that regulate metabolism
74
Insulin
metabolic effect
75
Well-Fed State: Insulin and its Effects
76
Glucose and Insulin
more blood glucose leads to - more insulin secretion - less glucagon secretion what makes this happen - islet of Langerhanss elevated [ATP] closes this channel, reducing K+ efflux and leading to...
77
ATP-Gated K+ Channel
remember - normally elevated [ATP] closes this channel, leading to insulin secretion type 2 diabetes treatment: sulfonylurea drugs stimulate insulin secretion: glyburide, glipizide, glimepiride
78
The fed state
Liver - Glycogen synthesis - Glycolysis - Fatty acid synthesis (-) glycogenolysis (-) gluconeogenesis (-) fatty acid oxidation GLUT2 Glucokinase (hexokinase IV) Phosphorylase a to phosphorylase b High F-2,6-BP Acetyl-CoA carboxylase Muscle GLUT4 to surface Glycogen synthesis Adipose GLUT4 to surface Synthesis of TAGs
79
The fasted state
Liver glycogenolysis Gluconeogenesis (-) glycogen synthesis (-) glycolysis (-) acetyl-CoA carboxylase Low F-2,6-BP Muscle Adipose Breakdown of TAGs
80
Epinephrine (Fast)!
ready to fight or flee
81
Cortisol (Slow)!
released from the adrenal cortex in response to stress (long-term stress hormone) acts slowly, increasing the fuel supply increases the release of FAs from adipose and the synthesis of glucose, glycogen, and TAG in the liver. May result in weight gain no evidence that supplements can lower weight by lowering [cortisol] Glucocorticoid and stress hormone In essence, this does the opposite of insulin Cortisol is released in response to stress and low blood glucose Hydrocortisone if used as a medication – is anti-inflammatory.
82
Starvation
Fed: protein - may be converted to fats (low efficiency) carbohydrates - maybe stored as glycogen - maybe stored as fat (75% efficiency) lipids - maybe stored as a fat (95% efficiency) starved 1. glycogen (liver & muscle) is depleted within ~12 hours 2. within ~24 hours, blood [glucose] begins to fall - insulin secretion decreases - glucagon secretion increases 3. these signal TAG mobilization & use 4. to provide fuel for the brain
83
Starvation
first 12-24 hours - fatty acids to acetyl-CoA - liver glycogen to glucose to acetyl-CoA max: ~12 hours after glucose & glycogen are depleted: - fatty acids to acetyl-CoA (continuing) no net conversion to glucose - protein to AA's to pyruvate to glucose - fat to ketone bodies to brain etc - (fat to glycerol [from TAG's] to glucose
84
Starvation
liver - glycogenolysis gluconeogenesis fatty acid oxidation ketone body formation amino acid oxidation muscle - fatty acid oxidation - protein breakdown adipose - breakdown of TAGs
85
Regulation of Feeding Behavior
“-atide”, “-glutide” Trulicity, Ozempic, Rybelsus, Wegovy, Mounjaro GLP-1 decreases blood glucose by enhancing the secretion of insulin. It also decreases glucagon secretion. And even increases taste sensitivity in the tongue (this is fun!). This is great for diabetics! Additionally, GLP-1 (and its agonists are pro-satiety) →Weight loss! (shortage)
86
Summary of Hormonal Regulation
glycogen - insulin: not broken down in muscle or liver but synthesized in muscles and liver - glucagon: broken down in the liver, not synthesized in the liver - epinephrine: broken down in muscle and liver, not synthesized in muscle and liver - cortisol: *blank* glucose - insulin: not and liver, glucose uptake: done in muscle and liver broken down in the liver, glycolysis: happens in the muscle and liver - glucagon: synthesized in the liver, glycolysis does not take place in the liver
87
Major regulated steps
Glycolysis hexokinase – P of glucose PFK-1 – P of glucose-6-P pyruvate kinase – phosphoenolpyruvate to pyruvate Gluconeogenesis pyruvate carboxylase - oxaloacetate phosphoenolpyruvate carboxykinase - PPEpyruvate fructose-1,6-bisphosphatase – removes PFK-1 P glucose-6-phosphatase – removes hexokinases P Glycogen synthesis glycogen synthase Glycogenolysis (phosphorylase kinase) glycogen phosphorylase Pentose shunt glucose-6-phosphate dehydrogenase – send it down the side path
88
Major regulated steps con’t
TCA cycle (pyruvate dehydrogenase) isocitrate dehydrogenase a-ketoglutarate dehydrogenase Oxidative phosphorylation levels of ADP/ATP Fatty acid oxidation carnitine acyl transferase 1 – cytoplasm to matrix Fatty acid biosynthesis acetyl-CoA carboxylase – makes malonyl Fatty acid storage hormone-sensitive lipase Urea cycle carbamoyl phosphate synthetase-1
89
Key junction points
Glucose-6-phosphate - glycogen synthesis/glycogenolysis glycolysis/gluconeogenesis pentose phosphate shunt Pyruvate - to acetyl-CoA - to oxaloacetate - oxidation by TCA fatty acid synthesis gluconeogenesis TCA cycle intermediate Acetyl-CoA - TCA cycle fatty acid synthesis ketone bodies cholesterol, steroids, bile salts Citrate - TCA cycle fatty acid synthesis
90
Regulation of fuel metabolism
Hormone - Insulin islet b cells Release - high glucose Liver - glycogenesis glycolysis FA synthesis - glycogenolysis, gluconeogenesis Muscle - glucose uptake glycogenesis Adipose - glucose uptake Counter-regulatory hormones hormone - Glucagon islet a cells release - low-glucose liver - glycogenolysis - gluconeogenesis epinephrine - adrenal medulla release - acute stress liver - glycogenolysis muscle - glycogenolysis to lactate adipose - HSL
91
Key, direct actions of insulin
Glycolysis - Stimulation: PFK-1 - via gene expression pyruvate kinase - via gene expression PFK-2/FBPase-2 - via gene expression Gluconeogenesis - inhibition: PFK-2/FBPase-2 via gene expression Glycogen synthesis - Stimulation: glycogen synthase Glycogenolysis - inhibition: phosphorylase kinase glycogen phosphorylase TCA cycle - Stimulation: pyruvate dehydrogenase Fatty acid oxidation - inhibition: hormone-sensitive lipase Fatty acid biosynthesis - Stimulation: acetyl-CoA carboxylase
92
Key, direct actions of glucagon
Glycolysis - Inhibition: PFK-1 (via PFK-2/FBPase-2) pyruvate kinase Gluconeogenesis - Stimulation: fructose-1,6-bisphosphatase (via PFK-2/FBPase-2) Glycogen synthesis - inhibition: glycogen synthase Glycogenolysis - stimulation: phosphorylase kinase glycogen phosphorylase TCA cycle Fatty acid oxidation - stimulation: hormone-sensitive lipase Fatty acid biosynthesis - inhibition: acetyl-CoA carboxylase
93
Key, direct actions of epinephrine
Glycogen synthesis - inhibition: glycogen synthase Glycogenolysis - stimulation: phosphorylase kinase glycogen phosphorylase TCA cycle - stmulation: pyruvate dehydrogenase (via Ca++ activation of phosphatase) Fatty acid oxidation - stimulation: hormone-sensitive lipase Fatty acid biosynthesis - inhibition: acetyl-CoA carboxylase
94
How many b.p.’s does a relaxed, closed circular piece of DNA with Lk = 100 have? A. 100 B. 200 C. 1050 D. 1000 E. 2000
C. 1050
95
Increasing the Lk of this piece of DNA from 100 to 102 will lead to... A. An increase in b.p.’s/turn and & negative supercoiling B. Adecreaseinb.p.’s/turnand& negative supercoiling C. Anincreaseinb.p.’s/turnand& positive supercoiling D. A decrease in b.p.’s/turn and & positive supercoiling
D. A decrease in b.p.’s/turn and & positive supercoiling
96
if a piece of DNA has 12,600 bp's and a Lk of 1000 it is underwound relaxed overwound
underwound
97
if a piece of DBA has 10500 bp's and an Lk of 1050 it will form a negative supercoil a positive supercoil neither of the above; it will be relaxed
a positive supercoil
98
underwinding DNA may result in any of the following except strand separation increasing the Lk negative supercoiling cruciform DNA
increasing the Lk
99
which of the following inhibits bacterial topoisomerases actinomycin D, acridine, and rifampicin puromycin and tetracyclines ciprofloxacin and levofloxacin irinotecan and topotecan
ciprofloxacin and levofloxacin
100
camptothecin, irinotecan and topotecan inhibit bacterial type I topoisomerase bacterial type II topoisomerases human type I topoisomerases
human type I topoisomerases
101
the typical error rate for DNA replication in E.coli after all proofreading is 1 in 100 10,000 1,000,000 10^7 10^9
10^9
102
which of the following inhibits both ribonucleotide reductase and DNA replication cisplatin oxaliplatin gemcitabine acridine
gemcitabine
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gemcitabine inhibits DNA synthesis topoisomerase RNA transcription protein translation
DNA synthesis
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Which of the following inhibits bacterial, but not human, RNA polymerase? A. Actinomycin D B. Acridine C. Rifampicin D. α-amantin
C. Rifampicin
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the genetic material in the SARS-CoV2 virus is DNA RNA the spike protein the N protein
RNA
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the Pfizer-BiioNTech and Moderna vaccines contain which of the following RNA DNA the SARS-CoV2 spike protein inactivated SARS-CoV2 virus
RNA
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the typical error rate for protein translation is about 1 in 100 10,000 1,000,000 10^7 10^9
10,000
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which of the following inhibits protein synthesis actinomycin D, acridine, and rifampicin puromycin and tetracyclines tunicamycin irinotecan and topotecan
puromycin and tetracyclines
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Eukaryotic protein synthesis is inhibited by ___? A. α-sarcin and ricin B. Chloramphenicol and erythromycin C. Clindamycin and streptomycin D. Puromycin and tetracycline
A. α-sarcin and ricin
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tunicamycin blocks DNA replication RNA Transcription protein translation protein glycosylation reverse transcriptase
protein glycosylation
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Most protein modification takes place in the ___? A. Cytosol B. Ribosome C. Nucleus D. Endoplasmic Reticulum E. Mitochondria
D. Endoplasmic Reticulum
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Diet Components
Nutrients – Carbohydrates, lipids, protein (energy & more) – Vitamins, minerals (no energy) – Water Non-nutrients: – Alcohol – Phytochemicals (plant-derived, bio-active) – Pigments – Additives
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Two “E”s
“Essential:” does not simply mean “necessary;” must be included in the diet * Energy: energy stored in chemical bonds; molecules stored until energy is used: – Carbohydrates: 4 kcal/g – Protein: 4 kcal/g – Fat (lipids): 9 kcal/g – Alcohol: 7 kcal/g
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Nutrients (narrowly defined)
* Vitamins: essential organic nutrients, required in small amounts; do not supply energy; may be degraded * Minerals (metal ions): required for structure (Ca: bones & teeth) or function (Fe, Mg); indestructible * Water: essential
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Nutritional Standards
* American & Canadian standards (1997-): Dietary Reference Intakes (DRI) * Age- and sex-specific * Estimated Average Requirements (EAR) * Recommended Dietary Allowances (RDA): supported by extensive research * Adequate Intakes (AI): supported by some research * Tolerable Upper Intake Levels (UL)
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EAR and RDA Compared (1 of 2)
The Estimated Average Requirement (EAR) for a nutrient is the amount that meets the needs of about half of the population (shown here by the red line). The Recommended Dietary Allowance (RDA) for a nutrient (shown here In green) is set well above the EAR. meeting the needs of about 99% of the population.
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Recommended Intakes of Nutrients and Energy
nutrients - enough for 99% of the subpopulation energy - average = RDA
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Views of Nutrient Intakes
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Notes about the DRI’s
* They apply to healthy people. * For nutrients, remember 99%. * Meant to apply to foods, not supplements * Average requirements over time – OK to have ups and downs * (We will discuss Daily Values later.)
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Nutrition deficiency ... and assessment nutrition deficiency ... and assessment
beginning/cause here is what is happening inside the body: - primary deficiency caused by inadequate diet or secondary deficiency caused by problems inside the body - declining nutrient stores - abnormal functions inside the body - physical (outward) signs and symptoms how can the health care provider tell? - diet history - health history - laboratory tests - physical examination and anthropometric measures
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Nutrition and Health
* Earlier, and in developing countries, disease associated with deficiency: – Scurvy – Vitamin C – Rickets – Vitamin D * Today, in developed countries, chronic diseases often associated with excess: – Heart disease (#1 cause of death in U.S.) – Cancers – Stroke – Diabetes
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Healthy Diet (RPW, Chap. 2)
* General Principles: ABCD+V: * Adequacy: enough of each nutrient & energy * Balance: enough, but not too much, of each * Calorie-control (& Energy Density) * Nutrient Density (next 3 slides; g/kcal) * Variety
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Comparison: Nutrient & Energy Density of Two Breakfast Options
nutrient-dense breakfast - energy density: 500 kcal/450 g = 1.1 nutrient-poor breakfast - energy density: 500 kcal/144 g = 3.5 nutrient density comparison (fraction of rec. amount)
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Nutrient Density
* Amount of a given nutrient per (kilo)calorie * Example #1: – 1 cup of ice cream: 170 mg Ca++/265 kcal. – 1 cup of nonfat milk: 300 mg Ca++/85 kcal * Example #2: Next slide
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Nutrient Density: the Potato
Oven-Baked Potato, with skin: 220 kcal +: – 0.07 mg Riboflavin, 3.33 mg Niacin – 2.75 mg Iron – 16 mg Sodium, 844 mg Potassium * McDonald’s small french fries: 207 kcal +: – 0 mg Riboflavin, 1.94 mg Niacin – 0.53 mg Iron – 135 mg Sodium, 469 mg Potassium
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Dietary Guidelines
* See the Dietary Guidelines for Americans, 2020-2025 (links on Blackboard) * Key recommendations (RPW, p. 41) – Focus on healthy eating patterns – Focus on variety, nutrient density, & amount – Limit intake of added sugar, sat. fats, Na+ – Shift to healthier food, and beverage choices – Support healthy eating patterns for everyone.
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healthy eating plate
healthy oils - use healthy oils (olive and canola oil) for cooking on salad, and at the table. Limit butter avoids trans fats the more veggies - and the greater the variety - the better. Potatoes and french fries do not count lol eat plenty of fruits of all colors drink water, tea, or coffee. Limit milk/dairy eat a variety of whole grains like oats, whole grain pasta, and brown rice. Limit refined grains like white rcs and white bread choose fish, poultry, beans and nuts; limits red meat and cheese; avoid bacon, cold cuts and other processed meats
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Estimated Calorie Requirements
* Amount depends on age and sex * Sedentary – Adults: 1600-2600 kcal * Moderately Active – Adults: 1800-2800 kcal * Active – Adults: 2000-3000 kcal
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Estimated Energy Needs for Sedentary Adults
women 19-25 yr: 2000 26-50 yr: 1800 51+ yr: 1600 men 19-25 yr: 2600 26-40 yr: 2400 41-60 yr: 2200 61+ yr: 2000
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Recommended Daily Intakes
for a person consuming 2,000 kcal/day * Fruit Group: 2 cups (4 servings) * Vegetable Group: 2.5 cups (5 servings) – Dark green: 11⁄2 cups/week – Red & orange: 51⁄2 cups/week – Legumes (dry beans): 11⁄2 cups/week – Starchy: 5 cups/week – Other: 4 cups/week
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Recommended Daily Intakes for a person consuming 2,000 kcal/day
* Grain Group: 6 ounce-equivalents – Whole grains: 3 oz.-equiv. – Other grains: 3 oz.-equiv. * Protein foods: 5.5 ounce-equivalents * Dairy Group: 3 cups * Oils: 6 tsp
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What about the rest of us?
Appendix 3, Table A3-1 suggests amounts of food form the various groups for those who consume less or more than 2000 kcal/day. Excerpts on the following slide.
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USDA Food Patterns: Fruits
Fruits contribute folate, vitamin A, vitamin C, potassium, and fiber. Consume a variety of fruits, and choose whole or cut-up fruits more often than fruit juice. Apples, apricots, avocados, bananas, blueberries, cantaloupe, cherries, grapefruit, grapes, guava, honeydew, kiwi, mango, nectarines, oranges, papaya, peaches, pears, pineapples, plums, raspberries, strawberries, tangerines, watermelon; dried fruit (dates, figs, prunes, raisins); 100% fruit juices Limit these fruits that contain solid fats and/or added sugars: Canned or frozen fruit in syrup; juices, punches, -ades, and fruit drinks with added sugars; tried plantains 1 c fruit = 1 c fresh, frozen, or canned fruit 1/2 c dried fruit 1 c 100% FruitUSDA Food Patterns: Vegetables Juice
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USDA Food Patterns: Vegetables
Vegetables contribute folate, vitamin A. vitamin C, vitamin K. vitamin E. magnesium, potassium, and fiber. Consume a variety of vegetables each day, and choose from all five subgroups several times a week. Dark-green vegetables: Broccoli and leafy greens such as arugula, beet greens, bok choy, collard greens, kale, mustard greens, romaine lettuce, spinach, turnip greens. watercress Red and orange vegetables: Carrots, carrot juice, pumpkin, red bell peppers, sweet potatoes, tomatoes, tomato juice, vegetable juice, winter squash (acorn, butternut) Legumes: Black beans, black-eyed peas, garbanzo beans (chickpeas), kidney beans, lentils, navy beans, pinto beans, soybeans and soy products such as tofu, split peas, white beans
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USDA Food Patterns: Vegetables (cont.)
Vegetables (continued from the previous slide Starchy vegetables: Cassava, corn, green peas. hominy. lima beans, potatoes Other vegetables: Artichokes, asparagus, bamboo shoots, bean sprouts, beets, brussels sprouts, cabbages, cactus, cauliflower, celery, cucumbers, eggplant. green beans, green bell peppers, iceberg lettuce. mushrooms, okra, onions, seaweed, snow peas, zucchini Limit these vegetables that contain solid fats and/or added sugars: Baked beans, candied sweet potatoes. coleslaw. french fries, potato salad, and refried beans. scalloped potatoes. tempura vegetables 1 c vegetables = 1 c cut-up raw or cooked vegetables 1 c cooked legumes 1 c vegetable Juice 2 c raw, leafy greens
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USDA Food Patterns: Grains
Grains contribute folate. niacin, riboflavin, thiamin, iron, magnesium, selenium, and fiber. Make most (at least half) of the grain selections whole grains. Whole grains: amaranth, barley, brown rice, buckwheat, bulgur, cornmeal, millet. oats, quinoa. rye. wheat, wild rice and whole-grain products such as breads. cereals. crackers, and pastas; popcorn Enriched refined products: bagels, breads. cereals, pasta (couscous, macaroni, spaghetti), pretzels, white rice, rolls, tortillas Limit these grains that contain solid fats and/or added sugars: Biscuits, cakes, cookies, cornbread, crackers, croissants, doughnuts, fried rice, granola, muffins, pastries, pies, presweetened cereals, taco shells 1 oz grains= 1 slice bread 1/2 c cooked rice, pasta, or cereal 1 oz dry pasta or rice 1 c ready-to-eat cereal 3 c popped popcorn
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USDA Food Patterns: Protein Foods
Protein foods contribute protein, essential fatty acids, niacin, thiamin, vitamin B6, vitamin B12, iron, magnesium, potassium, and zinc. Choose a variety of protein foods from the three subgroups, including seafood in place of meat or poultry twice a week. Seafood: Fish (catfish, cod, flounder, haddock, halibut, herring, mackerel, pollock, salmon, sardines, sea bass, snapper, trout, tuna), shellfish (clams, crab, lobster, mussels, oysters, scallops, shrimp) Meats, poultry, eggs: Lean or low-fat meats (fat-trimmed beef, game, ham, lamb, pork. veal), poultry (no skin), eggs Nuts, seeds, soy products: Unsalted nuts (almonds, cashews, filberts, pecans, pistachios, walnuts), seeds (flaxseeds, pumpkin seeds, sesame seeds, sunflower seeds), legumes, soy products (textured vegetable protein, tofu, tempeh), peanut butter, peanuts Limit these foods that contain solid fats and/or added sugars: Bacon; baked beans; fried meat, seafood, poultry, eggs, or tofu; refried beans: ground beef; hot dogs; luncheon meats; marbled steaks; poultry with skin: sausages; spare ribs 1 oz protein foods= 1 oz cooked lean meat, poultry, or seafood 1 egg 1⁄4 c cooked legumes or tofu 1 tbs peanut butter 1⁄2 z nuts or seeds
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USDA Food Patterns: Milk & Milk Prods.
Milk and milk products contribute protein, riboflavin, vitamin B12, calcium, potassium, and, when fortified, vitamin A and vitamin D. Make fat-free or low-fat choices. Choose other calcium-rich foods if you don't consume milk. Fat-free or 1% low-fat milk and fat-free or 1% low-fat milk products such as buttermilk, cheeses, cottage cheese, yogurt; fat- free fortified soy milk Limit these milk products that contain solid fats and/or added sugars: 2% reduced-fat milk and whole milk; 2% reduced-fat and whole- milk products such as cheeses, cottage cheese, and yogurt; flavored milk with added sugars such as chocolate milk, custard, frozen yogurt, ice cream, milk shakes, pudding, sherbet; fortified soy milk 1 c milk or milk product = 1 c milk, yogurt, or fortified soy milk 1 1⁄2 oz natural cheese 2 oz processed cheese
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USDA Food Patterns: Oils
ils are not a food group, but are featured here because they contribute vitamin E and essential fatty acids. Use oils instead of solid fats, when possible. Liquid vegetable oils such as canola, corn, flaxseed, nut, olive, peanut, safflower, sesame, soybean, sunflower oils; mayonnaise, oil-based salad dressing, soft trans-fat-free margarine; unsaturated oils that occur naturally in foods such as avocados, fatty fish, nuts, olives, seeds (flaxseeds, sesame seeds), shellfish Limit these solid fats: Butter, animal fats, stick margarine, shortening 1 tsp oil = 1 tsp vegetable oil 1 tsp soft margarine 1 tbs low-fat mayonnaise 2 tbs light salad dressing
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Is your serving a “serving?”
* Most bagels today weigh 4+ ounces, equal to 4+ servings!
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What you need to know (typical questions)
* On average, how many servings per day of fruit should a person who consumes 2000 kcal per day have? * If Table A2-1 & A3-1 (DGA 2010, Table 2-3 and Appendix 7) information is given: On average, how many servings per day of whole grains should a Moderately Active 25-year-old woman have?
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Grains: not all are the same
* As-is * Refined * Enriched or Fortified (+ Fe, thiamin, riboflavin, niacin, folate) * Whole-grain
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Daily Values (DV)
* Average recommended daily intake for a person on a 2000-kcal. diet (Note: average, not based on age or sex) * See inside of the back cover of RPW for a list. * The number on the label is the fraction (%) of the DV of a given nutrient in one serving. * Utility of DV is to compare foods, not to accurately determine adequacy for a given individual.
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Personal Daily Values
* Some DV’s can be ‘personalized:’ – Fat: 30% of kcal intake (9 kcal/g) [65g] – Saturated fat: 10% of kcal intake (9 kcal/g) [20g] – Carbohydrate: 60% of kcal intake (4 kcal/g) [300g] – Fiber: 11.5g/1000 kcal intake [23g, or ~25g] (proposed change: 14g/kcal) – Protein: 10% of kcal intake (4 kcal/g) [50g] * Others (cholesterol [300 mg – same for all adults], vitamins, minerals)
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Claims on food labels
nutrient health structure-function
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Nutrient Claims
* Indicates the specific content of a nutrient. * FDA defines and regulates (Link to claims allowed by FDA on Blackboard) * E.g., cholesterol-free: – <2 mg cholesterol/serving – ≤ 2 g saturated fat/serving * E.g., high fiber: 5 g or more per serving * See RPW Glossary, p. 61
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Health Claims
* Describes association between nutrient/food and a health problem. * FDA approval is required (Link to claims allowed by FDA on Blackboard) * Different from Structure-Function Claims, which do not require FDA approval * “A list” example: Ca and reduced risk for osteoporosis: Ca ≥ 20% of DV; P ≤ Ca * More examples: next 2 slides
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More “A” health claims (examples)
* Folate and neural tube defects * Low fat, low saturated fat and low cholesterol, and coronary heart disease * Saturated fat, cholesterol, trans fat and heart disease * Foods with soluble fiber and coronary heart disease * Whole grain foods and risk of heart disease and certain cancers
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More “A” health claims (examples)
* Low sodium & adequate potassium, and hypertension & stroke * Non-sugar sweeteners and dental caries * Fluoridated water and dental caries * Low fat and cancer * Fiber-containing foods and cancer * Fruits and vegetables and cancer
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Structure-Function Claims
* No FDA approval required * Must not mention any disease or symptom * Compare: – H.C.: “May reduce the risk of heart disease.” – S.-F.C.: “Promotes a healthy heart.” * Examples: – “Builds strong bones.” “Improves memory” “Slows aging.” “Guards against colds,
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What is the RDA for this nutrient (vitamin or mineral) and population?
#3 which is 62 #2 is the EAR
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Which of the following has the highest Ca nutrient density? (data for 1 serving, showing % of DV of Ca [1000mg]) * Cereal #1: 1⁄2 cup, 100 kcal, 2% of DV (20 mg) * Cereal #2: 1 cup, 100 kcal, 4% of DV (40 mg) * Cereal #3: 1 cup, 200 kcal, 2% of DV (20 mg) * Cereal #4: 1⁄2 cup, 300 kcal, 8% of DV (80 mg)
* Cereal #2: 1 cup, 100 kcal, 4% of DV (40 mg) cereal #2: 40mg/100 kcal = 0.40 mg/kcal or cereal #2: 4% of DV/100 kcal = 0.040%/kcal
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Which of the following has the highest Zinc nutrient density? Shown: g/serving, % Zn DV, kcal/serving 1. W.C: 47g, 30%, 160 kcal 2. S.W.B: 55g, 15%, 200 kcal 3. O.C.C.: 25g, 25%, 100 kcal 4. T.O.S: 56g, 35%, 210 kcal 5. Ch.: 30g, 25%, 110 kcal
3. O.C.C.: 25g, 25%, 100 kcal 25% of DV/100 kcal = 0.250%/kcal
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The folate RDA for a 19-30-y/o woman is 400 μg. and the UL is 1000 μg. This means that ... 1. The average 19-30- y/o woman needs 400 μg./day. 2. It is probably safe for a 19-30-y/o woman to consume 1000 μg./day. 3. Both of the above.
2. It is probably safe for a 19-30-y/o woman to consume 1000 μg./day.
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On average, how many cups (servings) per day of vegetables should a person who consumes 2000 kcal per day have? 1. 0.5(1) 2. 1 (2) 3. 1.5(3) 4. 2 (4) 5. 2.5(5) 6. 3 (6)
5. 2.5(5)
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Preview of next question On average, how many oz.-eq. per day of whole grains should a moderately active 25-year-old woman have? 1. 2.0-2.5 2. 3.0-3.5 3. 4.0-4.5 4. 5 5. 6-7 6. 7-8
2. 3.0-3.5
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Which of the following is not a connection made by an FDA-allowed Health Claim? 1. Cholesterol intake and hypertension 2. Fat intake and heart disease 3. Folate intake and neural tube defects 4. Sodium intake and hypertension 5. Non-sugar sweeteners and tooth decay
1. Cholesterol intake and hypertension
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“A list” health claims (examples)
* Folate and neural tube defects * Low fat, low saturated fat and low cholesterol, and coronary heart disease * Saturated fat, cholesterol, trans fat and heart disease * Foods with soluble fiber and coronary heart disease * Whole grain foods and risk of heart disease and certain cancers
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More “A” health claims (examples)
* Low sodium & adequate potassium, and hypertension & stroke * Non-sugar sweeteners and dental caries
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“Personal” Daily Values
The following information will be supplied on exam #4, and you may need it this morning: - fat: 30% of caloric intake – Saturated fat: 10% of caloric intake – Carbohydrates: 60% of caloric intake – Protein: 10% of caloric intake – Fiber: 11.5g/1000 kcal
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For an adult consuming 2400 kcal/day, what is the personal D.V. of fat? 1. 65g 2. 80g 3. 100g 4. 300g 5. 720g
2. 80g For an adult consuming 2400 kcal/day, what is the personal D.V. of fat? * 30% x 2400 kcal = 720 kcal * 720 kcal / 9 kcal/g = 80 g
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One serving of Girl Scout Thin Mints (4 cookies) contains 8g of fat. What fraction of this person’s personal D.V. is that? 1. 8% 2. 10% 3. 12%
2. 10% Personal D.V. = 80 g 8 g / 80 g = 10%
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Excessive consumption of EtOH leads to all of the following... 1. DecreaseinpH. 2. Decrease in [NADH]. 3. Increased synthesis of fatty acids. 4. Increased formation of ketone bodies.
2. Decrease in [NADH].
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Alcohol Metabolism: liver (cont.)
(1) EtOH + NAD+ → Acetaldehyde + NADH + H+ (2) Acetaldehyde + CoA + NAD+ → Acetyl CoA + NADH + H+ [Catalyzed by (1) alcohol dehydrogenase and (2) acetaldehyde dehydrogenase] * Consequences of consuming alcohol over the liver’s ability to metabolize it: – Decrease in pH (increase in H+) – NADH inhibits CAC – Acetaldehyde: – Acetyl-CoA accumulates, and begins to be transformed into fatty acids (fatty liver, fibrosis, cirrhosis) and ketone bodies (ketosis)
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Which has the lower Km for EtOH, alcohol dehydrogenase, or the MEOS enzyme? 1. ADH 2. MEOSenzymes
1. ADH
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MEOS
* Besides ADH, the liver has a microsomal ethanol-oxidizing system. * Metabolizes alcohol and various drugs. * ADH has Km=0.04 mM for EtOH. MEOS has Km=11 mM for EtOH.
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At an EtOH concentration of 1.0 mM, which enzyme will be most actively metabolizing the EtOH? 1. Alcohol dehydrogenase 2. MEOS enzymes
1. Alcohol dehydrogenase
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At an EtOH concentration of 15 mM, which enzyme(s) will be actively metabolizing the EtOH? 1. Alcohol dehydrogenase 2. MEOS enzymes 3. Both 4. Neither
3. Both
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MEOS
In addition to ADH, the liver also has a microsomal ethanol-oxidizing system. * Metabolizes alcohol and various drugs. * ADH has Km=0.04 mM for EtOH. MEOS has Km=11 mM for EtOH. * Repeated high blood [EtOH] stimulates the synthesis of MEOS enzymes. * At high [EtOH], EtOH metabolized more than drugs, resulting in elevated [drug] – a potentially serious problem.
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disulfiram inhibits ___ if a person who is taking this drug consumes alcohol, that person's blood serum level of ___ will increase, resulting in ___ 1. alcohol dehydrogenase, ethanol, flushing (redness) of the face 2. alcohol dehydrogenase, ethanol, ketosis 3. acetaldehyde dehydrogenase, ethanol, formation of fatty acids in the liver 4. acetaldehyde dehydrogenase, acetaldehyde, flushing (redness) of the face 5. acetaldehyde dehydrogenase, acetaldehyde, ketosis
4. acetaldehyde dehydrogenase, acetaldehyde, flushing (redness) of the face
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Acetaldehyde
Causes and consequences of acetaldehyde accumulation (highly reactive and toxic): – Excess consumption of alcohol leads to increased acetaldehyde formation. * Symptoms: alcohol flushing (redness), nausea, headache – Disulfiram inhibits acetaldehyde dehydrogenase. * a drug sometimes used to treat alcoholism
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Alcohol abuse commonly leads to a _____ deficiency. 1. Niacin 2. Riboflavin 3. Thiamin 4. Vitamin E 5. Vitamin K
3. Thiamin
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Alcohol Abuse and Metabolism
Most common vitamin deficiencies: folate, thiamine, B6, B12, D, A
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Alcohol & Nutrition
1⁄2 oz. ethanol in: – 5 oz. wine (100 kcal) – 10 oz. wine cooler (135 kcal) – 12 oz. beer (150 kcal; light: 80-130 kcal) – 11⁄2 oz. distilled liquor (100-110 kcal) Absorption through stomach walls – faster on an empty stomach
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Alcohol Metabolism & Absorption
Alcohol dehydrogenase breaks down some alcohol in the stomach; men generally have more than women, leading to a higher tolerance. * EtOH is absorbed by gastric mucosa, but even more rapidly by small intestinal mucosa (much greater surface area). * Fat delays gastric emptying, and thereby slows EtOH absorption.
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Alcohol Metabolism: liver
From the digestive tract, EtOH is transported to the liver for metabolism. * The liver (alcohol dehydrogenase) can metabolize ~1/2 oz. alcohol per hour; if the input is greater, the excess is transported to other cells. * During a fast, alcohol dehydrogenase may be broken down (to provide energy); this decreases the liver’s ability to metabolize alcohol.
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Alcohol Metabolism: liver (cont.)
(1) EtOH + NAD+ → Acetaldehyde + NADH + H+ (2) Acetaldehyde + CoA + NAD+ → Acetyl CoA + NADH + H+ [Catalyzed by (1) alcohol dehydrogenase and (2) acetaldehyde dehydrogenase] Consequences of consuming alcohol in excess of the liver’s ability to metabolize it: – Decrease in pH (increase in H+) – NADH inhibits CAC – Acetaldehyde: see following slide – Acetyl-CoA accumulates, and begins to be transformed into fatty acids (fatty liver, fibrosis, cirrhosis) and ketone bodies (ketosis)
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Acetaldehyde
Causes and consequences of acetaldehyde accumulation (highly reactive and toxic): – Excess consumption of alcohol leads to increased acetaldehyde formation. – Some populations have an inactive isoform of acetaldehyde dehydrogenase: unable to catabolize acetaldehyde, so it accumulates. * Symptoms: alcohol flushing (redness), nausea, headache * associated with lower incidence of alcoholism – Disulfiram inhibits acetaldehyde dehydrogenase. * a drug sometimes used to treat alcoholism
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MEOS
In addition to ADH, the liver also has a microsomal ethanol-oxidizing system. * Metabolizes alcohol and various drugs. * ADH has Km=0.04 mM for EtOH. MEOS has Km=11 mM for EtOH. * Repeated high blood [EtOH] stimulates the synthesis of MEOS enzymes. * At high [EtOH], EtOH metabolized more than drugs, resulting in elevated [drug] – a potentially serious problem.
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MEOS (continued)
If a heavy drinker stops drinking, the elevated [MEOS enzymes] may metabolize drugs more rapidly. * Such fluctuations may make it difficult to determine correct dosages.
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Alcohol in the brain
Regions affected by elevated [EtOH]: – Frontal lobe (judgment & reasoning) – Midbrain (speech and vision) – Cerebellum (vol. muscle control; may lead to staggering and slurred speech) – Pons, medulla oblongata (respiration and heart action)
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Alcohol and Weight
Moderately heavy drinkers (who have to metabolize the moderately high amount of alcohol they consume) have greater energy (calorie) intake and tend to gain weight (esp. “central obesity”). * Very heavy drinkers generally eat poorly and often suffer from malnutrition (don’t consume enough nutrients and lose weight).
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Alcohol Abuse and Metabolism
Folate deficiency – Not retained by the liver – Over-excreted by kidney – Poorly retained and absorbed by the intestine Thiamine deficiency – Reduced intake and poor absorption – Wernicke-Korsakoff syndrome (paralysis of eye muscles, poor muscle coordination, impaired memory)
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Alcohol Abuse and Metabolism
Vitamin B6 deficiency – De-protected, degraded by alcohol – Impairs production of red blood cells Vitamin B12 deficiency – Poorly absorbed by the intestine Vitamin D deficiency – Insufficient activation by the liver
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Alcohol Abuse and Metabolism
Vitamin A deficiency – Retinol not converted to retinal in eyes – Retinal not converted to retinoic acid in liver Summary: folate, thiamine, B6, B12, D, A
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