560D Clinical Biochem - Hessberger Flashcards
A client with iron deficiency anemia despite eating meat and green leafy vegetables. What other nutrient is needed to properly absorb iron.
Vitamin C
Which 3 factors can increase the likelihood of getting iron deficiency anemia?
Heavy menstruation
Deficiency of copper
Celiac disease
Why is it important to differentiate iron deficiency anemia from Thalassemia?
Blood transfusions in Thalassemia can lead to iron overload (and iron is oxidative)
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?
High altitude
Increased 2,3-Bisphosphoglycerate
Decreased pH (acidity)
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.
Hepicidin
Synthesized by the liver and controls homeostasis
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):
Decreased pH; Increased CO2
What nutrient binds to intrinsic factor to be properly absorbed? Where is it absorbed in the GI?
Vit B12
Ileum
Folate trap occurs when there is deficient amounts of Vit B12 and folate gets “trapped” in the form of _____________.
5-Methy-THF
Folic acid is composed of (3 parts):
Pterin, PABA, glutamic acid
Which aminotransferase plays a role in the malate-aspartate shuttle and has subcellular isoenzymes located in the mitochondria and cytosol?
Aspartate amniotransferase (AST)
Glutathione is composed of (3 parts):
Gamma-glutamyl, cysteinyl, and glycine
How many ATP are utilized in the Gamma-glutamyl cycle to resynthesize glutathione?
3 ATP
What 4 factors interfere with the Iodide uptake and utilization by the thyroid?
Low TSH
Low ATP
Competing halogens like bromide and chloride
Goitrogenic foods like soy and uncooked cruciferous vegetables
What minerals are selectively symported into the thyroid follicular cell from the bloodstream for the creation of thyroid hormones?
Iodide and Sodium (Sodium Iodide Symporter NIS)
Iodothyronine Deiodinase 2 converts T4-T3. what cofactor is needed for proper function?
Selenium
Thyroperoxidase (TPO) is responsible for catalyzing what 4 reactions?
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
Insulin’s effects on target tissue include all the following (4)
Increased cell uptake of glucose
Increased glycogen synthesis
Increased potassium uptake
Increased FA synthesis
Intra-abdominal (visceral) fat is more dangerous than subcutaneous fat because:
Increases inflammatory cytokines
Increases free FA
May increase insulin resistance and ER stress
Glucagon rises in fasting state and controls metabolism by: (3)
Blocking glycolytic enzymes
Increasing PEP-carboxylase (gluconeogensis)
Inhibiting glycogen synthase (glycogenesis)
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?
> or = 6.5
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 __________.
Free Fatty Acids = non-esterified FA
Peroxisome Proliferator Activated Receptor (PPAR) is important in FA and glucose metabolism. What factors/nutrients can assist in activation of these receptors: (4)
PUFA and 9-cis-retinoic acid
Exercise
Zinc and Magnesium
Vitamin E
Insulin resistance leads to increased cardiovascular disease risk through which of the following:(3)
Increased PAI-1
Increased inflammation through peroxidation
Increased TG, VLDL, and LDL
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:
The liver regurgitates conjugated bilirubin into the blood, and decline of conjugated bilirubin entering the GI
How is porphyrin different from porphyrinogen?
Porphyrins are the oxidized form of porphytinogen.
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.
How many ATP are needed to create active ALA synthase (fold it, activate it, and transport it into the mitochondria)?
2 ATP
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
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.
What’s the abbreviation for Isoleucine?
Ile
List the essential Amino Acids (9):
PVT TIM HALL
Phe
Val
Thr
Trp
Ile
Met
His
Arg
Leu
Lys
List the large neutral AA (6)
Trp Tyr Phe Leu Ile Met
NH3 is _______ and acts to help buffer _______ environments.
mildly basic
acidic
In the urea cycle, Arginase requires what cofactor to convert Arg -> Orn + urea?
Mn++
In the urea cycle, Citrulline combines with Aspartate to form __________ via the enzyme ASS (argininosuccinate synthase).
Argininosuccinate
In the urea cycle, Ornathine + Carbamoyl phosphate -> PO4 + Citrulline is catalyzed by what enzyme?
Mitochondrial Ornathine Tricaboxylase (OTC)
A defect in the ura cycle enzyme argininosuccinate lyase, will lead to the accumulation of what substrate?
Argininosuccinate
Arganine conversion into Agmatine via the enzyme arganine decarboxylase requires what cofactor?
P5P (B6)
Elevated ADMA (asymmetric dimethylarginine) ________ nitric oxide synthesis and angiogenesis.
inhibits
BCAA are converted to alpha-ketoacids via BCAA Transaminase. This enzyme requires the cofactor:
P5P (B6)
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
The following reaction requires what two enzymes?
Threonine -1-> alpha-ketobutryate +NH3 -2-> propionyl CoA
Threonine Dehydrotase
Branched Chain alpha-Ketoacid Dehydrogenase Complex (BCKDC)
Histidine is converted to histamine via Histidine Decarboxylase- What cofactor is required?
P5P (B6)
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)
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
Phenylalanine hydroxylase (PAH) requires what nutrients for conversion of Phe –> Tyr
Iron, B3, BH4
Conversion of norepinephrine -> epinephrine via the enzyme Catechol-O-Methytransferase (COMT) utilizes what nutrient in this reaction?
SAMe
Tryptophane monooxygenase (ie tryptophan hydroxylase) like tyrosine hydroxylase and phenylalanine hydroxylase require what cofactor for proper function?
Iron (Fe), tetrahydrobiopterin (BH4)
Degradation of serotonin -> 5HIAA via monoamine oxidase (MAO) requires what two minerals for functionality?
Cu, Fe
Alpha-amino-N-butyric acid (AANB) may be elevated in alcoholism. What may be deficient when AANB is elevated?
B6
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)
Methionine adenosyltransferase converts Met -> to _________ with the assistance of ATP and H2O.
SAMe
Both Methionine Synthase (MS) and Betaine Homocycteine Methyltransferase (BHMT) can convert homocycteine to methionine with the assistance of what mineral?
Zn++
Heme iron, B6, betaine and SAMe assist Cystathionine Beta-Synthase (CBS) in activating the transulfuration pathway in oxidative stress to convert homocysteine + ________ -> cystathionine.
Serine
Homocycteine is considered the _____________ form of homocystine
Reduced
Supplements with what vitamin raise betaine levels?
folic acid
T/F: Oxidative stress activates the transulfation pathway to divert sulfur-containing amino acids into creation of glutathione, a major antioxidant.
TRUE
Glutathione reductase converts GSSG -> 2 GSH. What nutrients assist this process?
FAD, NAD, Cu++
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
What AA is a precursor to serine and component of glutahione?
Glycine
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
Serine Hydroxymethyltransferase (SHMT) interconverts serine and glycine with assistance of what nutrients?
5,10-Methylene THF, P5P, Mn++
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
What nutrients are required for the creation of connective tissue components Hydroxyproline (HPro) and Hyroxylysine (HLys)?
Vit C, iron
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
Proteins require the use of _________ for the conversion of ketoacids in acetyl-CoA.
B1, B2, B3, B5 and lipoate
Carbohydrates require the use of __________ for the conversion to acetyl-coA and entry into he TCA cycle.
B1, B2, B3, B5 and lipoate
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++
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
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
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
Isocitrate dehydrogenase converts isocitrate to a-KG with the assitance of (3 cofactors): ________
Mg++, Mn++, NAD++
Inhibition of CoQ10 synthesis from statin drugs will tpically reveal elevations in urinary ____________.
Hydroxymethylglutarate
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)
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
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
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)
Elevations in lactate, pyruvate, and beta-hydroxybuyrate indicate abnormalities in __________ metabolism.
Carbohydrate
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
Formiminotransferase utilizes _________ to convert FIGLU to glutamate.
THF
The marker for biotin deficiency is ________
Beta-hydroxyisovalerate
Catabolism of several AA and odd-chain FA eventually yields methymalonyl CoA (MMA). Conversion via enzyme MMA mutase requires the vitamin _________
B12
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)
Breakdown of serotonin into 5HIAA occurs via he enzyme ____1_____ which requires ____2_____ (2 cofactors).
MAO
Cu++ and Fe++