560D Clinical Biochem - Hessberger Flashcards
1
Q
A client with iron deficiency anemia despite eating meat and green leafy vegetables. What other nutrient is needed to properly absorb iron.
A
Vitamin C
2
Q
Which 3 factors can increase the likelihood of getting iron deficiency anemia?
A
Heavy menstruation
Deficiency of copper
Celiac disease
3
Q
Why is it important to differentiate iron deficiency anemia from Thalassemia?
A
Blood transfusions in Thalassemia can lead to iron overload (and iron is oxidative)
4
Q
Sickle cell anemia is caused by a point mutation leading to structural instability of the RBC. What 3 conditions can increase stress leading to increased deoxyhemoglobin in sickle cell crisis?
A
High altitude
Increased 2,3-Bisphosphoglycerate
Decreased pH (acidity)
5
Q
Anemia of chronic disease can be caused from prolonged inflammation (IL-6, cytokines, infection), which increases level of ____________ to sequester iron in the tissue so that germs can’t use the iron to reproduce.
A
Hepicidin
Synthesized by the liver and controls homeostasis
6
Q
Increased levels of deoxyhemoglobin from altitudes can precipitate a Sickle Cell Crisis. The “T” form of hemoglobin (ie deoxyhemoglobin) is more predominant in peripheral body tissue with (in terms of pH and respiration):
A
Decreased pH; Increased CO2
7
Q
What nutrient binds to intrinsic factor to be properly absorbed? Where is it absorbed in the GI?
A
Vit B12
Ileum
8
Q
Folate trap occurs when there is deficient amounts of Vit B12 and folate gets “trapped” in the form of _____________.
A
5-Methy-THF
9
Q
Folic acid is composed of (3 parts):
A
Pterin, PABA, glutamic acid
10
Q
Which aminotransferase plays a role in the malate-aspartate shuttle and has subcellular isoenzymes located in the mitochondria and cytosol?
A
Aspartate amniotransferase (AST)
11
Q
Glutathione is composed of (3 parts):
A
Gamma-glutamyl, cysteinyl, and glycine
12
Q
How many ATP are utilized in the Gamma-glutamyl cycle to resynthesize glutathione?
A
3 ATP
13
Q
What 4 factors interfere with the Iodide uptake and utilization by the thyroid?
A
Low TSH
Low ATP
Competing halogens like bromide and chloride
Goitrogenic foods like soy and uncooked cruciferous vegetables
14
Q
What minerals are selectively symported into the thyroid follicular cell from the bloodstream for the creation of thyroid hormones?
A
Iodide and Sodium (Sodium Iodide Symporter NIS)
15
Q
Iodothyronine Deiodinase 2 converts T4-T3. what cofactor is needed for proper function?
A
Selenium
16
Q
Thyroperoxidase (TPO) is responsible for catalyzing what 4 reactions?
A
Coupling of DIT with DIT to form T4
Coupling of MIT with DIT to form T3
Iodination, joining of Iodine to thyroglobulin
Oxidization of Iodide to Iodine
17
Q
Insulin’s effects on target tissue include all the following (4)
A
Increased cell uptake of glucose
Increased glycogen synthesis
Increased potassium uptake
Increased FA synthesis
18
Q
Intra-abdominal (visceral) fat is more dangerous than subcutaneous fat because:
A
Increases inflammatory cytokines
Increases free FA
May increase insulin resistance and ER stress
19
Q
Glucagon rises in fasting state and controls metabolism by: (3)
A
Blocking glycolytic enzymes
Increasing PEP-carboxylase (gluconeogensis)
Inhibiting glycogen synthase (glycogenesis)
20
Q
Hyperglycemia can lead to glycation (glycosylation) reactions. One such glycation reaction with hemoglobin A leads to HbA1C. What level of HbA1C is indicative of diabetes?
A
> or = 6.5
21
Q
One of the maladaptive responses to insulin resistance is dyslipidemia. Increased activity of vascular lipoprotein lipase leads to increased chylomicron and VLDL release of non-estrified or __________.
A
Free Fatty Acids = non-esterified FA
22
Q
Peroxisome Proliferator Activated Receptor (PPAR) is important in FA and glucose metabolism. What factors/nutrients can assist in activation of these receptors: (4)
A
PUFA and 9-cis-retinoic acid
Exercise
Zinc and Magnesium
Vitamin E
23
Q
Insulin resistance leads to increased cardiovascular disease risk through which of the following:(3)
A
Increased PAI-1
Increased inflammation through peroxidation
Increased TG, VLDL, and LDL
24
Q
Obstruction of the bile duct from gallstones (extrahepatic cholestasis) can cause symptoms of pale clay colored stool and dark urine upon standing. This occurs because:
A
The liver regurgitates conjugated bilirubin into the blood, and decline of conjugated bilirubin entering the GI
25
How is porphyrin different from porphyrinogen?
Porphyrins are the oxidized form of porphytinogen.
26
How can porphyrias arise from low caloric/low glucose diets?
Because ALA synthase 1 will be upregulated to push heme biosynthesis
Glucose inhibits ALAS1, so it is automatically upregulated in the absence of glucose. This is why glucose is given IV to people with acute porphyrias and why it is important for people with porphyrias to avoid crash dieting and low-carb diets.
27
How many ATP are needed to create active ALA synthase (fold it, activate it, and transport it into the mitochondria)?
2 ATP
28
The first step in heme degradation utilizes heme oxygenase to create biliverden. What reductant is required for this step of the pathway to function?
NADPH
29
Which enzyme in the heme biosynthesis pathway contains Zinc and is located in the cytosol?
Delta-ALA Dehydrate
This enzyme converts 2 ALA into porphobilinogen and is very sensitive to heavy metals like lead because they replace the zinc.
30
What's the abbreviation for Isoleucine?
Ile
31
List the essential Amino Acids (9):
PVT TIM HALL
Phe
Val
Thr
Trp
Ile
Met
His
Arg
Leu
Lys
32
List the large neutral AA (6)
```
Trp
Tyr
Phe
Leu
Ile
Met
```
33
NH3 is _______ and acts to help buffer _______ environments.
mildly basic
| acidic
34
In the urea cycle, Arginase requires what cofactor to convert Arg -> Orn + urea?
Mn++
35
In the urea cycle, Citrulline combines with Aspartate to form __________ via the enzyme ASS (argininosuccinate synthase).
Argininosuccinate
36
In the urea cycle, Ornathine + Carbamoyl phosphate -> PO4 + Citrulline is catalyzed by what enzyme?
Mitochondrial Ornathine Tricaboxylase (OTC)
37
A defect in the ura cycle enzyme argininosuccinate lyase, will lead to the accumulation of what substrate?
Argininosuccinate
38
Arganine conversion into Agmatine via the enzyme arganine decarboxylase requires what cofactor?
P5P (B6)
39
Elevated ADMA (asymmetric dimethylarginine) ________ nitric oxide synthesis and angiogenesis.
inhibits
40
BCAA are converted to alpha-ketoacids via BCAA Transaminase. This enzyme requires the cofactor:
P5P (B6)
41
Branched Chain Ketoacid Dehydrogenase Complex (BCKDC) attaches Coenzyme A to alpha-ketoacids. The nutrients utilized in this reaction (either substrates or cofactors) are:
B1, B2, B3, B5, Lipoic Acid
42
The following reaction requires what two enzymes?
| Threonine -1-> alpha-ketobutryate +NH3 -2-> propionyl CoA
Threonine Dehydrotase
Branched Chain alpha-Ketoacid Dehydrogenase Complex (BCKDC)
43
Histidine is converted to histamine via Histidine Decarboxylase- What cofactor is required?
P5P (B6)
44
Lysine does NOT undergo the initial transamination requiring B6 but downstream conversion of alpha-aminoadipic acid (a-AAA) to alpha-ketoadipate does require B6. What nutrient is required for the initial conversion of Lys -> Saccharopine?
B3 (Niacin)
45
Conversion of Lys ->->-> Carnitine is important because carnitine shuttles FA into the mitochondria for Beta-oxidation. Along with Lys, what nutrients would improve enzymatic function of this pathway?
```
SAMe,
a-KG,
B3,
FE++,
Vit C
```
46
Phenylalanine hydroxylase (PAH) requires what nutrients for conversion of Phe --> Tyr
Iron, B3, BH4
47
Conversion of norepinephrine -> epinephrine via the enzyme Catechol-O-Methytransferase (COMT) utilizes what nutrient in this reaction?
SAMe
48
Tryptophane monooxygenase (ie tryptophan hydroxylase) like tyrosine hydroxylase and phenylalanine hydroxylase require what cofactor for proper function?
Iron (Fe), tetrahydrobiopterin (BH4)
49
Degradation of serotonin -> 5HIAA via monoamine oxidase (MAO) requires what two minerals for functionality?
Cu, Fe
50
Alpha-amino-N-butyric acid (AANB) may be elevated in alcoholism. What may be deficient when AANB is elevated?
B6
51
What enzyme requiring B6 converts Glutamate -> Gamma-amino-N-butyric acid (GABA)?
Catechol-O-methyltransferase
Succinate semialdehyde dehydrogenase
Glutamic acid decarboxylase (GAD)
Monoamine oxidase
Glutamic acid decarboxylase (GAD)
52
Methionine adenosyltransferase converts Met -> to _________ with the assistance of ATP and H2O.
SAMe
53
Both Methionine Synthase (MS) and Betaine Homocycteine Methyltransferase (BHMT) can convert homocycteine to methionine with the assistance of what mineral?
Zn++
54
Heme iron, B6, betaine and SAMe assist Cystathionine Beta-Synthase (CBS) in activating the transulfuration pathway in oxidative stress to convert homocysteine + ________ -> cystathionine.
Serine
55
Homocycteine is considered the _____________ form of homocystine
Reduced
56
Supplements with what vitamin raise betaine levels?
folic acid
57
T/F: Oxidative stress activates the transulfation pathway to divert sulfur-containing amino acids into creation of glutathione, a major antioxidant.
TRUE
58
Glutathione reductase converts GSSG -> 2 GSH. What nutrients assist this process?
FAD, NAD, Cu++
59
Taurine, utilized in the skelatal muscle and bile, can be created from cycteine with the assistance of what nutrients (4)?
Fe, P5P, FAD, NAD
Iron, P5P, FAD, NAD
60
What AA is a precursor to serine and component of glutahione?
Glycine
61
While the Glycine Cleavage System utilizes Gly, NAD, and THF in the chain reactions to create 5,10-Methylene THF, it also contains a __________ binding domain and _____________ prosthetic group.
FAD
| Lipoic Acid
62
Serine Hydroxymethyltransferase (SHMT) interconverts serine and glycine with assistance of what nutrients?
5,10-Methylene THF, P5P, Mn++
63
Sarcosine (aka N-methylglycine) can be a storage of buffer for excess methyl groups that are transferred from ___________ to Glycine to create sarcosine.
SAMe
| Via enzyme glycine-N-methyltransferase
64
What nutrients are required for the creation of connective tissue components Hydroxyproline (HPro) and Hyroxylysine (HLys)?
Vit C, iron
65
In biochemistry, an enzyme ends with "-ase" like lactase, a sugar ends in "-ose" like lactose, and the ionized form of an organic acid ends in "____"
"-ate" butryate
66
Proteins require the use of _________ for the conversion of ketoacids in acetyl-CoA.
B1, B2, B3, B5 and lipoate
67
Carbohydrates require the use of __________ for the conversion to acetyl-coA and entry into he TCA cycle.
B1, B2, B3, B5 and lipoate
68
Citrate, cis-aconitate, Isocitrate are located at the beginning of the TCA cycle. Elevations of Cis-aconotate can indicate dysfunction of the enzyme aconitase, which requires the mineral _______ and cysteine.
Fe++
69
Low urinary Citrate levels have been associated with kidney stone formation. What kind of diet may increase the risk of kidney stone formation?
High protein, low carbohydrate
70
High MMA can inhibit the ________ transporter, leading to elevations of it in the urine. Hence elevations in this TCA cycle intermediate can be from B12 deficiency.
Malate
71
The conversion of alpha-ketoglutarate (a-KG) to succinyl-CoA via enzyme a-KG-dehydrogenase is similar to other dehydragenase complexes (like BCKDC) in that it also requires the same nutrients for functionality: ______________.
B1, B2, B3, B5 and lipoate
72
Isocitrate dehydrogenase converts isocitrate to a-KG with the assitance of (3 cofactors): ________
Mg++, Mn++, NAD++
73
Inhibition of CoQ10 synthesis from statin drugs will tpically reveal elevations in urinary ____________.
Hydroxymethylglutarate
74
High levels of suberate, adipate and ethylmalonae can be reduced with Vitamin _______, which is utilized by the flavoprotein enzyme Fatty Acyl-CoA Dehydrogenase,
B2 (riboflavin)
75
Elevations in lacate can indicate disruption of carbohydrate metabolism and the body's need to regenerate the vitamin ________ to keep the glycolytic pathway functioning.
B3, niacin
76
high urinary oxalates can occur from which of the following? (3)
high intake of spinach, peanuts, beets, and chocolate
Production from GI bacteria
Absence of Oxalobacter formigenes
77
Elevations in lactate can indicate disruption of carbohydrate metabolism and the body's need to regenerate the vitamin/cofactor _____________ to keep the glycolytic pathway functional
NAD+ (B3)
78
Elevations in lactate, pyruvate, and beta-hydroxybuyrate indicate abnormalities in __________ metabolism.
Carbohydrate
79
It is important to note that elevations in Xanthurenate indicate that you should NOT supplement with any amino acids till you have first supplemented with Vitamin ______ because transamination function is impaired.
B6
80
Formiminotransferase utilizes _________ to convert FIGLU to glutamate.
THF
81
The marker for biotin deficiency is ________
Beta-hydroxyisovalerate
82
Catabolism of several AA and odd-chain FA eventually yields methymalonyl CoA (MMA). Conversion via enzyme MMA mutase requires the vitamin _________
B12
83
Elevations of the jynurenin pathway constituent 3-hydroxykynurenin leads to its side conversion into xnathurenate, which spills into the urine and can indicate insufficiency of vitamin _______.
B6 (pyridoxine)
84
Breakdown of serotonin into 5HIAA occurs via he enzyme ____1_____ which requires ____2_____ (2 cofactors).
MAO
Cu++ and Fe++
85
Homovanillate is the degradation product of ________ catabolism.
Dopamine
86
COMT utilizes _________ and __________ to degrade the catecholamines dopamine, norepinephrine and epinephrine.
SAMe and Mg++
87
High protein diets increase activity of ACMSD (alpha-amino-beta-carboxymuconate-E-semialdehude decarboxylase) which converts 2-amino-3-carboxymuconate into the organic acid ______________ and leads to the upregulation of NO synthase, shifts Tryptophan metabolism away from B3 formation, and leads to the activation of inflammatory chemokines.
Picolinate
88
Copper deficiency can lead to reduced activity of dpamine beta-monooxygenase (DBM) which converts dopamine to norepinephrine. Hence in copper deficiency you can find elevated urinary ____1____ and reduced urinary ____2____.
1. HVA (OA metabolite of dopamine elevated)
| 2. VMA (OA metabolite of NE reduced)
89
The ratio of kynurenate to quinolinate (KYNA:QUIN) is important because?
KYN blocks NMDA receptors reducing glutamate excitoxicity
90
Homogentisate (HGA) may be elevated in urine due to excess supplementation of the amino acid _____________.
Tyrosine
91
_________________ is a metabolite of Tyrosine, cell proliferation marker, and may indicate normal tissue growth or tumor growth.
p-Hydroxyphenyllacetate (HPLA)
92
When the DNA oxidative damage marker _________ is seen elevated in urine with high QUIN and HPLA, this indicates sustained inflammatory responses and increased cell proliferation rates caused by increased ROS, which lead to DNA damage via oxidation.
8-hydroxy-2'-deoxyguanosine (8-OHDG)
93
High ammonia levels from urea cycle dysfunction can lead to accumulation of ___1____. Treatment with __2/3___ may help urea cycle function better and decrease urinary ____1___ levels.
Orotate
Arginine
Mg++
94
High urinary _________, a marker for phase I & II liver detoxification, may indicate exposure to pesticides, petrochemicals, alcohol and drugs.
Glucarate
95
Elevations in urinary pyroglutamate indicates that supplementation with __________ maybe indicated.
NAC, Glycine, GSH, antioxidants, Mg++
96
Elevations in ___1____ from xylene exposure may warrant supplementation with ____2/3____ to assist cytochrome P450 oxidase enzymes and phase II conjugation reactions.
2-Methylhippurate
NAC
B3
97
Alpha-hydroxybuterate appears elevated in the urine when there has been a shift from trans-__1____ to trans- ___2____ to increase creation of ___3____.
methylation
sulfuration
GSH
98
Deficincy of the mineral _______ can lead to decreased incorporation of cystine into protein, allowing sulfate to spill into urine.
Zinc
99
Poor absorption of the AA Tryptophan can lead to the assumulation of the dysbiosis metabolite _______.
Indican
100
Clostridia species like C. Difficile can lead to elevations in several dysbiosis markers such as: (3)
Phenylpropionate
p-Cresol
3,4-Dihydroxyphenylpropionate
101
Bacterial ingestion of dietary polyphenols can lead to the creation of the intestinal dysbiosis markers ___________.
Benzoate, Hippurate, Phenylacetate, Phenylpropionate.
102
Elevations in benzoate and not hippurate indicate:
Difficulty with phase II conjugation
There is a need for B5
There is a need for Glycine
103
High urniary D-lactate may indicate a person: (3)
is ingesting too many carbs
ingesting too much Lactobacillus acidophilus or L. plantarum
has short bowl syndrome
104
Sugars ingested by yeast and fungi produce the intestinal dysbiosis marker:
D-Arabinitol
105
When considering toxic exposure, through what barriers and routes of entry can lipophilic toxins be absorbed? (4)
The skin
lymphatics
in utero
through the GI
106
The insecticide DDT, a chlorinated hydrocarbon pesticide, has been banned in the US since the 970's but is still causing toxic effects today because it's: (3)
a presistent toxin
still used overseas
bio accumulative
107
Toxins can cause cell injury by interfering with DNA regulatory mechanisms, increasing oxidative stress, and altering enzymatic function. The damage is extensive and cannot be easily repaired, the DNA itself will be damaged as indicated by a rise in___________.
8-OHDG
108
Testing toxin load can be complicated by deposition in different tissues like the extracellular matrix and the need to test for ___________ in the urine.
multiple metabolites
109
Advanced glycation end-products (AGE) are created when glucose reacts spontaneously with ____1____ on proteins to create ____2_____ products that spontaneously and irreversibly degrade to form AGE's.
1. Amino acids
| 2. Maillard reaction
110
Treatments to reduce AGE's and ALE's include:
Antioxidants to reduce oxidation
Normalizing plasma glucose levels
Phase I and II detox to remove RCOs
Activation of lysosome degradation
111
ALA + ALA --> porphobilinogen via the enzyme ___1___ which requires (cofactor) ____2____.
Delta-ALA dehydratase
| Zinc
112
Porphyrin accumulation indicates:
Decreased ability to degrade toxins
Decreased ability to oxygenate cells
decreased CYP enzymes
113
Iron deficiency blocks the last step of Heme creation, where iron is inserted into the protoporphyrin IX. Hence there's a rise in:
RBC protoporphyrin and Zn protoporphyrin
114
UROD is blocked by both ___1/2____. The difference between the two heavy metals is that ____3____ causes a high pentacarboxyporphyrin because it slows UROD down, making the last decarboxylation step difficult.
(a) As and Mercury (Hg), (b) Hg
Arsenic blocks UROD at the beginning step, while mercury blocks the last step of UROD.
115
Precoproporphyrin may elevate when _____ blocks the last step of UROD, leading to accumulation of pentacarboxyporphyrinogen, which is converted by CPOX to precoproporphyrin.
Mercury (Hg)
116
The heavy metal _______ causes preferential elevation in Copro I: Copro III because it blocks the early steps of UROD decarboxylation, leading to the accumulation of uroporphyringen I, which converts to coproporphyringen I.
Arsenic (As)
117
AST, ALT, CPK, and _____ are all enzymes that can be indicatos of liver damage, which in turn means impaired liver function
gamma-glutamyl transpeptidase
118
Elevations in total bilirubin levels indicte impaired degredation of heme as seen in Gilbert's syndrome. This indicates impaired ______, a pathway in phase II detoxification.
glucuronidation
119
Elevations in BUN indicate increased load of ammonia. Check OA profile, you find high orotate levels, which could indicate there is a genetic SNP in the enzyme:
Ornithine transcarboxylase (OTC)
120
CYP1A2 and CYP2E1 are important to remember because these pathways are activated by:
caffeine
Also activate by acetominophen
121
Alcohol, high protein diets, high brassica diets, saturated fats, steroid hormones, charcoal-broiled meats (AGE's), oranges, exhaust fumes, pesticides, niacin and riboflavin all have the following in common:
1. induce CYP enzymes
122
One of the 3 major pathways of the phase I detoxification includes:
Hydroxylation
123
Clearance of the compound _______ is used to determine activity level of phase I detoxification.
Caffeine
124
A low rate of caffeine clearance can indicate: (3)
genetic SNPs lowering phase I detox capacity
loss of liver function
low level of toxin exposure
125
Phase II detoxification involves conjugation of water soluble constituent to a functional group on the toxin. These conjugation reactions can occur:
- multiple times, creating different metabolites
- on carboxyl, hydroxyl or amine groups
- along different pathways, depending on substrate concentration
126
Location of the enzyme ___1____ in the ER right next to the cytochrome P450 enzymes enables it to reach the phase I metabolites before other phase II detox enzymes. The isoform ____2___ acts on the highest number of substrates (40%), including bile, morphine, and codeine.
UDP-glucuronyl transferase
| UGT2B4 (=2B7)
127
Immune responses can occur from the creation of __________ , like when acyl groups migrate from C1-acyl glucuronides to another protein, covalently bond this new protein, and create a substance that is now considered foreign and antigenic to the body.
haptens
128
The activated form of glucoronic acid __1____ is used in th glucuronidation reactions and is produced from the oidation of ____2_____.
UDP-glucuronic acid
| UDP-glucose
129
_______ are S-derivatives of N-acetylcysteine synthesized from glutathione.
Mercapturic acids
130
There are 2 major types of sulfotransferases. One type is membrane-bound in the golgi apparatus and sulfates GAG's and glycoproteins, while the other is located in the _____ and conjugates steroids, catacholamines, T4, bile acids, and xenobiotics.
Cytosol
131
Sulfate conjugation requires the activated form of sulfate, _________, which is created using the substrate SO4 +ATP and catalyzed by the enzyme ATP sulfurylase.
3-phosphoadenosine-5'-phosphosulfate (PAPS)
132
Amino Acid conjugation requires 2 steps. the first step is activation of the xenobiotic carboxylic acid using the enzyme __1____, which requires ATP and _______.
acyl synthetase
| B5
133
The rate of acetylation is important in detoxification because:
slow acetylators accumulate higher blood concentrations of the active drug
134
Biomethylation to remove arsenic requires the use of ______ (number) SAMe as a methyl donor.
2
135
Methylation for single carbon transfer is needed in far greater quantities for ___1____ than for ____2____.
Detoxification
| Catecholamine biosynthasis
136
T/F: Oral challenge with aspirin reveals higher glycine conjugate than glucuronides. This is a normal interpretation.
TRUE
137
Oral challenge with benzoic acid reveals high benzoate. Supplementation with __1__ and ___2___ will help with conversion of benzoate to hippurate.
glycine
| B5
138
Sideroblastic anemia is an X-linked condition where the enzyme called ____________________ is mutated, leading to excess iron in the RBC mitochondria.
Delta-aminolevulinic acid synthase
This is also the enzyme that controls the rate limiting step in heme synthesis.
139
What symptoms of iron deficiency anemia block hepcidin expression, leading to increased ferroportin and iron availability? (2)
Hypoxia: An absence of enough oxygen in the tissues to sustain bodily functions.
erythropoeisis: the production of red blood cells.
140
The Bohr effect explains that a decrease in the amount of oxygen associated with hemoglobin (Hb) due to a reduced affinity of oxygen for Hb is the result of:
Increased pCO2 and decreased pH
141
It is important to simultaneously check vitamin B12 and folate levels because administration of folic acid can mask vitamin B12 deficiency, leading to neurological demyelination that is often irreparable. The 2 constituents that accumulate in B12 deficiency, one of which competitively inhibits FA biosynthesis leading to increased myelin sheath turnover/degradation are:
Methylmalonyl CoA and homocysteine
142
GI conjugase enzymes hydrolyze folate to the monoglutamate form. What cofactor is needed for this reaction?
Zinc
143
Alanine aminotransferase (ALT) converts alpha-ketoglutarate into glutamate and alanine into:
Pyruvate
144
Gamma-glutamyl transpeptidase (GGT) is responsible for breaking down ......(a)...... into (b)
(a) GSH, (b) gamma-glutamylAA + cysteinylglycine
145
How can decreased levels of thyroid hormone impact vitamin A?
Impairs conversion of beta-carotene to vitamin A
146
The Alanine Cycle converts __ alanine from peripheral tissue into glucose in the liver during a fasting state, requires ATP and produces ___ ATP in peripheral tissues.
2, 5-7
147
Elevations in Cortisol have been implicated in insulin resistance. Name 3 actions of high cortisol levels
Increased gluconeogenesis
Increased FA synthesis
Increased glycogenolysis
148
True or False: Phosphofructokinase 1, Glucokinase, and Pyruvate Kinase are all upregulated in response to insulin.
TRUE
149
Glucagon rises in a fasting state and controls metabolism by: (3)
Blocking glycolytic enzymes
Inhibiting glycogen synthase
Increasing PEP-carboxykinase
150
Clients may be diagnosed as overweight if their BMI is:
25-29.9
151
High levels of ATP in the cell indicate increased energy reserves. Hence, high levels of ATP will:
Block activity of pyruvate kinase
| High ATP will shut down phosphofructokinase and pyruvate kinase of glycolysis to further slow production of more ATP.
152
The Cori cycle:
Converts 2 lactate into glucose
Is upregulated in a fasting state
Produces 2 ATP in peripheral tissues
153
Adiponectin assists in: (3)
Decreased inflammation
Increased glucose uptake
Decreased fat accumulation
154
Activation of the "thrifty" gene during maternal under- or over-nutrition may lead to under- or over-weight babies, which causes an:
Increased risk of DM, CVD, and Obesity
155
One of the maladaptive responses in insulin resistance includes dyslipidemia. Increased activity of vascular lipoprotein lipase leads to increased chylomicron and VLDL release of non-esterified or __________________.
Free Fatty Acids
Non-esterified FA = Free FA
156
The correlation of hyperinsulinemia and increases in hypertension come from the hyperinsulinemia causing:
Increased sodium retention and uric acid retention
157
Delta-aminolevulinic acid (ALA synthase) creates delta-aminolevulinic acid from what substrates?
Succinyl CoA and glycine
158
The reabsorption of urobilinogens from the GI to the liver so they can be re-secreted into the bile is called the _________________.
Enterohepatic Urobilinogen Cycle
159
What is the abbreviation for Isoleucine?
Ile
160
What are the four conditionally essential amino acids? (4)
Arg, Gln, Gly, Tau
161
List the large neutral AA: (6)
Trp, Tyr, Phe, Leu, Ile, Met
162
If there is a defect in the SN1-SN2 transporter allowing Gln into the presynaptic nerve terminal, what will happen to Glu levels within the presynaptic nerve terminal?
Glu levels will decline unless the EEAC1 receptor can compensate
163
GS (Glutamine Synthetase) requires the use of what minerals to assist in the conversion of Glu -> Gln?
Mg++, Mn++
164
Periportal hepatic cells respond to increased local acidity by transporting ___(a)__ through the SNI-SN2 transporter to cleave it into __(b)__, which buffers the acidity.
a) Gln, (b) Glu + NH3
Glutamine gets broken down into Glutamate and NH3. NH3 is alkaline in nature and helps buffer acidity.
165
Gln can be cleaved to Glu + NH3 via PDG. This process is used in what 3 organs to help regulate/buffer acidic pH.
Kidney
Brain
Liver
166
A defect in the urea cycle enzyme argininosuccinate lyase, will lead to the accumulation of what substrate?
Argininosuccinate
167
The pathway Arg -> Orn + a-KG -> -> Pro for the creation of collagen via the enzymes arginase, ornithine aminotransferase and pyrroline-5-carbosylate reductase require what nutrients for proper activity?
Mn++, P5P, retinoic acid, B3, Mg++
168
Arg -> ADMA via PRMT (methionine dependent protein arginine N-methyltransferase) requires what nutrient?
SAMe
169
Conversion of threonine -> alpha-ketobutryate + NH3 -> propionyl CoA requires the use of what two enzymes?
Threonine Dehydratase,
| Branched Chain alpha-Ketoacid Dehydrogenase Complex (BCKDC)
170
Histamine can be degraded through hepatic (liver) diamine oxidase and aldehyde dehydrogenase OR through extra-hepatic pathways utilizing histamine N-methyltransferase. How do the nutrient requirements differ for these pathways?
Diamine Oxidase is copper-dependent
171
A reaction that forms intermediates in a metabolic pathway like in the TCA cycle from precursors that are not part of the original metabolic pathway is considered a(n) ______________ reaction.
Anaplerotic reaction
172
The central energy pathways begin with digestion and assimilation of fats, carbohydrates, and proteins. Long chain FA require the use of the _________________ shuttle to help them enter the mitochondrial for beta-oxidation.
Carnitine
173
The central energy pathways begin with digestion and assimilation of fats, carbohydrates, and proteins. Carbohydrates require the use of what 5 nutrients for conversion to acetyl-CoA and entry into the TCA cycle.
Vitamins B1, B2, B3, B5 and Lipoate
174
Asparagine (from asparagus) can be converted into aspartate. Aspartate is in a unique position to enter the TCA cycle through its conversion into the TCA cycle intermediate, __________________, via the enzyme AST (SGOT) and cofactor vitamin B6.
Oxaloacetate
175
Succinate is unique because it not only is one of the TCA cycle intermediates, but it can also feed electrons directly to complex II of the ETC, via succinate dehydrogenase. This enzyme requires (a) to function. Low levels of (b) may also raise levels of succinate and all the TCA cycle intermediates because the ETC becomes halted, causing a backup of the TCA cycle.
(a) FAD, (b) CoQ10
176
Elevations in suberate, adipate, and ethylmalonate indicate dysfunction of _______________ metabolism.
Fatty acid
177
Beta-hydroxybutyrate is a ketone body formed in diabetes (from the failure to utilize glucose appropriately) or from a low carbohydrate diet increasing dependency on FA oxidation. Both scenarios lead to a spill over of acetyl-CoA, which gets converted into beta-hydroxybutyrate. Treatment with what two minerals can help support the action of insulin and rebalance carbohydrate metabolism?
Chromium and vanadium
178
Insufficiency of vitamins B1, B2, B3, and B5 can lead to reduced enzymatic function of branched chain ketoacid dehydrogenase complex and causing increased urinary: (5)
alpha-keto-beta-methylvalerate
alpha-ketoisovalerate
alpha-ketoisocaproate
179
Elevation of the kynurenin pathway constituent 3-hydroxykynurenin leads to it's side conversion into xanthurenate, which spills into the urine and can indicate insufficiency of vitamin _______.
B6
180
Norepinephrine and epinephrine can be degraded into _________________ via the enzymes COMT and MAO.
Vanilmandelate
181
Deficiency of the mineral, ___________, can lead to decreased incorporation of cystine into protein, allowing sulfate to spill into the urine.
Zinc
182
High urinary D-Lactate may indicate a person: (3)
- Is ingesting too much Lactobacillus acidophilus or L. plantarum
- Has short bowel syndrome
- Is ingesting too many carbohydrates
183
Poor absorption of the amino acid, ___(a)___, can lead to accumulation of the dysbiosis metabolite indican.
(a) Tryptophan, (b) Indican
184
When considering toxic exposures, through what barriers and routes of entry can lipophilic (fat loving) toxins be absorbed?
Through the lymphatics
In utero
Through the skin
Through the GI tract
185
The insecticide DDT, a chlorinated hydrocarbon pesticide, has been banned in the USA since the 1970s but is still causing toxic effects today because it is: (3)
A persistent toxin
Still used over seas
Bioaccumulative
186
Two major types of organotoxins are xylene and phthalates. Since both can be stored in adipose, measuring the hepatic detoxification product ________________ in the urine, can reveal that xylene is still being processed long after the initial exposure.
2-methylhippurate
187
The 4 concurrent decarboxylation steps in the porphyrinogen pathway convert (a) to coproporphyrinogen III via the enzyme (b)
(a) uroporphyrinogen III, (b) Uroporphyrinogen decarboxylase
188
The first step in the formation of heme (porphyrinogen pathway) involves the substrates glycine and succinyl CoA being converted to _(a)__ by the enzyme (b)
(a) delta-aminolevulinic acid, (b) delta-aminolevulinic acid synthase
189
The enzyme CPOX (coproporphyrinogen oxidase) converts coproporphyrinogen III to protoporphyrinogen IX and is blocked by the heavy metals ______.
Lead and Mercury
190
High ammonia can be from impaired degradation of proteins, impaired urea cycle, and even exercise. High ammonia can also be indicative of: (3)
excessive glutamine intake
bacterial overgrowth
deficiency of arginine
191
One of the three major pathways of phase I detoxification includes:
Hydroxylation
| Other ones are oxidation and reduction.
192
Cytochrome P450 enzymes function in the hydroxylation reactions for the activation of (a) and in the microsomal system located in the (b) for the detoxification of xenobiotics.
(a) vitamin D, (b) smooth ER
193
High caffeine clearance indicates:
upregulation of phase I detox
can be upregulated by high protein diet, smoking, and other toxins going through CYP1A2 and CYP2E1 pathways
194
The activated form of glucuronic acid, (a) , is used in glucuronidation reactions and is produced from the oxidation of (b) .
a) UDP-glucuronic acid, (b) UDP-glucose
195
Localization of the enzyme (a) in the ER right next to the cytochrome P450 enzymes enables it to reach the phase I metabolites before other phase II detox enzymes. The isoform (b) acts on the highest number of substrates (40%), including bile, morphine, and codeine.
(a) UDP-glucuronyl transferase, (b) UGT2B4 (=2B7)
196
There are two major types of sulfotransferases. One type is membrane-bound in the golgi apparatus and sulfates GAGs and glycoproteins, while the other is located in the __________ and conjugates steroids, catecholamines, T4, bile acids, and xenobiotics.
cytosol
197
Hippuric acid is created via activation of ___(a)____ with CoA and conjugation with the amino acid ____(b)_____.
(a), benzoic acid, (b) glycine
198
Methylation typically works on endogenous constituents, with O-methyl metabolites have ___(a)____ activity than the original molecule. The active methyl group used in methylation reactions is ____(b)____.
(a) greater, (b) SAMe
199
Match the nutrient depletion with the type of symptom/problem than can occur when the nutrient is depleted: B1 and B6 -
neurological symptoms
200
Match the nutrient depletion with the type of symptom/problem than can occur when the nutrient is depleted:B6 and B9
hematologic symptoms
201
Match the nutrient depletion with the type of symptom/problem than can occur when the nutrient is depleted: B1
Wernick-Korsakoff syndrome
202
Match the nutrient depletion with the type of symptom/problem than can occur when the nutrient is depleted: Vit D
osteoperosis
203
Match the pathways of alcohol degradation with the appropriate enzyme:
ethanol + NAD --> acetaldehyde + NADH
Alcohol dehydrogenase
204
Match the pathways of alcohol degradation with the appropriate enzyme: acetaldehyde +NAD --> acetate + NADH
Aldehyde dehydrogenase
205
Match the pathways of alcohol degradation with the appropriate enzyme: ethenol + NADPH --> acetaldehyde + NADP+
Cytochrome P450 CYP2E1
206
Match the appropriate detox function with the specific nutrient: Toxic metal binding/antiox protection
Vit C
207
Match the appropriate detox function with the specific nutrient:hepatic conjugation
glycine, sulfate
208
Match the appropriate detox function with the specific nutrient: glutathione regeneration
Se, Mn, Cu, Zn, NAC
209
Match the appropriate detox function with the specific nutrient: methyl donor
Met and SAMe
210
Match the appropriate detox function with the specific nutrient:-lead protection
Ca
211
Match the appropriate detox function with the specific nutrient: stimulation of phase I and II detox
cruciferous
