functional med november Flashcards
- What types of biochemical perturbations/lesions are predisposing and propagating factors involved in the etiology of chronic diseases?
a. Amino acid substitutions or deletions in protein primary structures - changes in higher order protein structures that affect structure and function - change cell architecture or enzyme activities. B. Toxicant may cause alterations in cell structural components or they may bind to enzyme active sites, blocking required biochemical pathways.
- How does early detection of nutrient deficiency prevent chronic degenerative disease?
a. Early detection can lead to interventions that restore nutrient levels to values that enhance the recovery of normal cellular and tissue function.
- How do standard therapeutic interventions for heart disease or depression affect a patient’s nutritional status?
a. Use of drugs like statins for atherosclerotic heart disease or SSRIs for depression serve to avert the short term effects of the disease, but they can exacerbate underlying nutrient insufficiencies or toxic effects.
- As of 2001 (the year of publication for reference 317 of Chapter 4), how many genetic mutations of PAH were known to cause some variant of PKU?
In what enzyme? phenylalanine _________
a. 400, phenylalanine hydroxylase
- What other enzyme is a principal cause of PKU?
hint _ _ _ cyclohydrolase
What is the biochemical relationship of this enzyme to the clearance of excess L-phenylalanine?
a. GTP cyclohydrolase
can have mutations that decrease the available levels of BH4 (Tetrahydrobiopterin)that is required as a coenzyme for Pulmonary hypertension (PAH)
- For enzymes with vitamin-derived cofactor requirements, is there any difference between the clinical outcome from a genetic alteration in the protein structure and dietary deficiency of the nutrient required for production of the cofactor?
a. No.
Differences in manifestations arise the age of onset and severity of outcome from strongly disrupting genetic mutations.
(CI 2.1) Why is it unusual to find elevated lipid peroxides when fat-soluble vitamins in serum are in their upper ranges? What does such a finding tell you about other nutrients that need evaluation?
• (CI 2.1) an indication that an individual has normal levels of protection against oxidative stress
- because many of the primary antioxidant functions are carried out by those vitamins, especially regarding biological membrane damage revealed by elevated lipid peroxides.
- The pattern found suggests that there may be elevated levels of membrane components that are easily oxidized, principally the polyunsaturated fatty acids.
(CI 2.2) Which vitamin insufficiencies are indicated by elevated branched chain keto acids in urine?
B1, B2, B3, folate and lipoic acid
B1, B2, B3, B5 and lipoic acid
B1, B2, B3, B12 and lipoic acid
B1, B2, B3, B6 and lipoic acid
• (CI 2.2) Elevated BCKA indicates low activity for the BCKA dehydrogenase complex that can be caused by deficiencies for one of its 5 B-vitamin-derived coenzymes, B1, B2, B3, B5 and lipoic acid.
(CI 2.3) How does urinary formiminoglutamate testing add clinical insight to homocysteine testing?
• (CI 2.3) Elevated HCys can be due to several factors, one of which is folate deficiency. Finding a normal level of FIGLU helps to rule that out as a cause.
What organ failure most directly causes multiple low essential trace elements to be found in blood or urine? Why do such patients frequently show only slowly improving trace element status?
r
• (CI 3.1) Failure of hydrochloric acid output by the stomach reduced the digestion of dietary protein and the accompanying release of bound multivalent elements. Supplementing the elements without correcting the stomach acid deficiency may be poorly effective because (1) foods are the major source of daily element intake and (2) lack of properly timed pH shifts can interfere with the sequence of events required fodelivering added elemental salts to absorptive surfaces in the small intestine. Free amino acids and small peptides from dietary protein are often required intermediate ligands for element absorption.
If you are called to review the records of a patient who has undergone multiple heavy metal detoxification procedures, what change in treatment is suspected when previously normal urinary mercury suddenly shows strong elevation?
• (CI 3.2) Rapid increase in Hg found in body fluids when no significant change in exposure has occurred could be due to either physician-guided chelation therapy or patient-administered forms of chelating agents such as sulfur amino acid that can mobilize Hg from deep sequestered sites such as bone.
What amino acid evaluation would come to mind for a patient with chronic thyroid insufficiency?
• Low tyrosine and phenylalanine
(pp 188-189) What effect does delayed specimen transport have on relative levels of glutamate (glu) and glutamine (gln)?
• (pp 188-189) Spontaneous hydrolysis of the amide side chain causes Gln conversion to Glu in specimens that are either delayed or warmed during transit.
(pp 222-230) The reciprocal regulation of transmethylation and transulfuration of HCys shown in Fig. 4.20 translates to decreased availability of HCys for reformation of Met.
What pattern of amino acids in plasma might indicate chronic presence of such effects in a patient?
why would this happen?
The reciprocal regulation of transmethylation and transulfuration of HCys shown in Fig. 4.20 translates to decreased availability of HCys for reformation of Met as shown in Fig. 2.11. The reduced flow of Met tends to reduce available active methyl (S-adnosylmethionine) for all methylation reactions shown in Fig. 2.11. Multiple clinical outcomes can be associated with these competing demands for homocysteine.
What body function uses the most amount of AA’s?
Protein synthesis is, by far, the greatest demand on absorbed amino acids, far outpacing other products such as neurotransmitters or hormones like thyroxin.
A consequence of this fact (Protein synthesis is, by far, the greatest demand on absorbed amino acids) is that patients who show dramatic responses to therapies of customized essential amino acids are most likely demonstrating clinical effects of ____ ____ ____.
This is especially true regarding the organs with greatest turnover rates like the __1__ and 2. In the 2, the only process that can approach the magnitude of amino acid demand for protein synthesis is glutathione synthesis in a patient under chronic, severe oxidative or toxicant stress.
restored organ reserve
GI tract and liver
(Fig 4.11) What compound is abbreviated “ADMA.” What cell regulator does elevated levels of ADMA in blood affect? What symptom is frequently produced?
ADMA stands for assymetric dimethylarginine
it inhibits nitric oxide synthase, regulating the multiple, powerful effects of that cell regulator.
Excessive ADMA frequently produces hypertension due to lack of NO to induce vasodilatation.
(Fig 4.17) What elemental cofactor is required for conversion of dopamine to norepinephrine? For what enzyme?
And what vitamin derivative?
• (Fig 4.17) Copper ions are a critical cofactors required by dopamine hydroxylase.
also needs ascorbate
why does finding a pattern of strongly elevated serine with low glycine on a plasma amino acid profile may be related to patient symptoms of poor growth, maldigestion, impaired cognition or excessive fatigue?
- Gly and Ser are related by a single reaction that transfers the hydroxymethyl group,
- they normally move up and down together on amino acid profiles.
- When they do not, then other pathway interferences are suspected, mainly glycine cleavage system
- genetic or toxicant interruption of that enzyme would tend to prevent the degradation of glycine.
- The resulting accumulation of glycine would tend to reduce activity of the Gly to Ser conversion, leading to such a pattern of elevated Gly and normal or low Ser.
-Since that pathway is a major source of single carbon for the THF pathways (Fig 2.11), multiple biosynthetic and methylation defect manifestations may be found.
finding a pattern of strongly elevated serine with low glycine on a plasma amino acid profile, Which micronutrients are potential causes or confounding factors?
That system may be activated by added vitamin B6 or folate.
finding a pattern of strongly elevated serine with low glycine on a plasma amino acid profile, : If your assessments indicate normal levels of those micronutrients (B6 or folate), what other explanation is likely for the amino acid abnormality pattern?
If various evaluations indicate normal levels of those vitamins, then a genetic polymorphism in the glycine cleavage system enzyme is indicated, as occurs in the condition known as non-ketotic hyperglycinemia.
finding a pattern of strongly elevated serine with low glycine on a plasma amino acid profile: What further information about health effects related to the pattern is suggested by the information in Fig. 4.23?
• (Fig’s 4.22 and 4.23). Since that pathway is a major source of single carbon for the THF pathways (Fig 2.11), multiple biosynthetic and methylation defect manifestations may be found.
Describe a typical procedure for producing a customized free-form amino acid product.
• (Fig 4.30b) performing a plasma amino acid profile and using the results to produce an essential amino acid mixture where the degrees of low levels in plasma govern amounts added for each amino acid. The usual dosing of the product for adults is a rounded teaspoon twice daily.
(CI 4.3) What amino acid imbalance is indicative of ornithine transcarbamylase deficiency? Why?
• (CI 4.3) Genetic polymorphisms in any of the four enzymes of the urea cycle tend to produce strong elevations of urea cycle intermediate products measured in profiles of plasma amino acids. In the case of OTC deficiency, the greatest elevation is usually in its substrate, ornithine.
pg 201 -
Antidepressants can deplete
- B vitamins, Se, Zn, GSH, Ca, Mg, Vit C
- Low plasma AA
- AA’s, Cu, mercury toxicity, lithium def. low cholesterol, low GABA
- Mg, Tauu, Vitamin E
- B vitamins, low plasma AA
- Arg, Arsenic, beta carotene, Iodine, Niacin, Se, Strontium, Vitamin C, zinc
B vitamins, Se, Zn, GSH, Ca, Mg, Vit C
Diabetes can cause what Nutrient Def?
- B vitamins, Se, Zn, GSH, Ca, Mg, Vit C
- Low plasma AA
- AA’s, Cu, mercury toxicity, lithium def. low cholesterol, low GABA
- Mg, Tauu, Vitamin E
- B vitamins, low plasma AA
- Arg, Arsenic, beta carotene, Iodine, Niacin, Se, Strontium, Vitamin C, zinc
Mg, Tauu, Vitamin E
Heart disease can be related to what nutrient def.
- B vitamins, Se, Zn, GSH, Ca, Mg, Vit C
- Low plasma AA
- AA’s, Cu, mercury toxicity, lithium def. low cholesterol, low GABA
- Mg, Tauu, Vitamin E
- B vitamins, low plasma AA
- Arg, Arsenic, beta carotene, Iodine, Niacin, Se, Strontium, Vitamin C, zinc
- oxidative stress, nutrient def. insufficiency of antioxidants, toxicity. Arginine, niacin, CoQ10, vitamin C, E, B vitamins
(not listed in book)–oxidative stress, nutrient def. insufficiency of antioxidants, toxicity. Arginine, niacin, CoQ10, vitamin C, E, B vitamins
Cancer related nutrient def.
- B vitamins, Se, Zn, GSH, Ca, Mg, Vit C
- Low plasma AA
- AA’s, Cu, mercury toxicity, lithium def. low cholesterol, low GABA
- Mg, Tauu, Vitamin E
- B vitamins, low plasma AA
- Arg, Arsenic, beta carotene, Iodine, Niacin, Se, Strontium, Vitamin C, zinc
arginine, arsenic toxicity, beta carotene, iodine, niacin, selenium, strontium, vit C, zinc
Chronic fatigue related nutrient def.
- B vitamins, Se, Zn, GSH, Ca, Mg, Vit C
- Low plasma AA
- AA’s, Cu, mercury toxicity, lithium def. low cholesterol, low GABA
- Mg, Tauu, Vitamin E
- B vitamins, low plasma AA
- Arg, Arsenic, beta carotene, Iodine, Niacin, Se, Strontium, Vitamin C, zinc
Low plasma AA
Depression related nutrient def.
- B vitamins, Se, Zn, GSH, Ca, Mg, Vit C
- Low plasma AA
- AA’s, Cu, mercury toxicity, lithium def. low cholesterol, low GABA
- Mg, Tauu, Vitamin E
- B vitamins, low plasma AA
- Arg, Arsenic, beta carotene, Iodine, Niacin, Se, Strontium, Vitamin C, zinc
B vitamins, low plasma AA
Autism related nutrient def.
- B vitamins, Se, Zn, GSH, Ca, Mg, Vit C
- Low plasma AA
- AA’s, Cu, mercury toxicity, lithium def. low cholesterol, low GABA
- Mg, Tauu, Vitamin E
- B vitamins, low plasma AA
- Arg, Arsenic, beta carotene, Iodine, Niacin, Se, Strontium, Vitamin C, zinc
AA metabolism, copper, mercury toxicity, lithium def. low cholesterol, low GABA (gamma-aminobutyric acid)
Why does direct testing of calcium in body fluids fail to reveal nutritional status of calcium?
what is the proper method?
Measuring calcium in body fluids or tissues provides only the status of ionic calcium that is highly regulated and shows little variation over a wide range of balance conditions.
Bone mineral density (BMD) provides the best measurement of calcium status. Calcium is mainly stored in the bones.
(CI 4.7) Corrections of what four amino acid insufficiencies are found to be helpful in anxiety? Why?
- Ly, Gly, Trp, Phe
- Lys, Gly, Tau, Phe
- Ly, Gly, Tau, Proline
- Lys, Gly, Tyr, Phe
• (CI 4.7) Patients with anxiety related to imbalanced brain neurotransmitter function may respond to amino acids that act directly as receptor antagonists (Lys, Gly, Tau) or serve as precursors to neurotransmitters (Phe).
What patterns indicate customized, free-form amino acids?
• Various patterns where some EAA are low and others are normal or elevated suggest specific pathways are activated causing individual amino acid depletions. This pattern is most famously found as low L-Trp in patients on SSRI medications that increase the demand for serotonin formation from tryptophan.
What AA patterns indicate glutathione stress? (6 AAs)
What 2 kinds of stress causes this?
What do the patterns of lower levels and greater numbers of those amino acids are found indicate?
• Low levels of the amino acids that either directly or indirectly participate in GSH formation (Met, Tau, HCys, Gly, Ser, Thr) may be due to chronic oxidative or toxicant stresses that chronically increase demand for glutathione that the liver attempts to supply via higher rates of GSH synthesis.
Patterns of lower levels and greater numbers of those amino acids are found low emerge, give indications of more and more severe GSH stress that may require more aggressive interventions with amino acids and investigation of causes.
(pp 272-273) Into what categories are the fatty acids typically placed on laboratory reports?
chain length within each greater category or desaturation level or
PUFA omega double bond position.
(pp 287-288) What fatty acid is part of the structure of the most active endocannabinoids?
(pp 287-288) The endocannabinoids of greatest physiological activity are derived from arachidonic acid.
(pp 298-299) Which omega-3 fatty acid tends to become persistently low in patients using fish oil supplements?
potentially clinically low levels of AA.
• (pp 298-299) When fish oil supplements are used excessively, the superior binding of the n-3 fatty acids to desaturase enzymes tends to suppress the desaturation of linoleic and GLA to form AA, casing potentially clinically low levels of AA.
(Fig. 5.2) Composition of which lipoprotein is largely revealed in measurements of both serum triglycerides and plasma fatty acids?
largely LDL particles.
• (Fig. 5.2) Since specimen collection for both serum triglycerides and plasma fatty acids is done in the fasting state, the circulating form of lipoprotein is largely LDL particles.
(Table 5.2) Which foods are particularly rich in linoleic acid?
- evening primrose, safflower, grape seed, sunflower and hemp
- Fish oil, avocado, coconut oil
- flax, primrose, or black current oils
- Palm oil, butter, cheese and meats
cooking oils? • coconut, cottonseed and peanut • corn, cottonseed and olive • corn, cottonseed and peanut • olive, cottonseed and peanut
(order of potency) evening primrose, safflower, grape seed, sunflower and hemp.
with the notable exception of olive oil, LA is a major ingredient in all of the oils commonly used in cooking, including corn, cottonseed and peanut.
(Fig 5.9) There is a requirement to perform a 2-carbon removal from the carboxyl group end of the 24:6n3 intermediate that is not possible inside mitochondria. What cellular organelle other than mitochondria is required for VLCFA degradation? What clinical consequence is common in pregnancy?
•
peroxisomes
The VLCFA intermediate must be transported out of the mitochondria and into the peroxisomes in order to generate DHA that is critical for infant brain development. Thus, infants delivered by women who are deficient in DHA take a long time to develop their own DHA levels from dietary precursors.
18:1n9
Linoleic acid (LA) Oleic Acid (OA) α-linolenic (ALA)
Oleic Acid (OA)
18:2n6
Linoleic acid (LA) Oleic Acid (OA) α-linolenic (ALA)
Linoleic acid (LA)
20:4n6
eicosapentaenoic acid (EPA) Arachidonic acid (AA) Linoleic acid (LA)
Arachidonic acid (AA)
20.5n3
eicosapentaenoic acid (EPA) Arachidonic acid (AA) α-linolenic (ALA)
eicosapentaenoic acid (EPA)
(Fig 5.12) What essential nutrient other than PUFAs is required to stimulate peroxisome proliferation? How does this broaden clinical outcomes due to deficiency of that nutrient?
• Vitamin A as, 9-cis-retinoic acid
(Fig 5.12) Activation of the PPAR requires simultaneous binding of a PUFA and vitamin A as, 9-cis-retinoic acid.
Since peroxisome proliferation is a fundamental cellular response to energetic and immunological stressors, any condition that might require those systems may be impacted by deficiencies of PUFAs or vitamin A.
what is PPAR?
Peroxisome proliferator-activated receptors (PPARs)
are ligand-activated transcription factors of nuclear hormone receptor superfamily.
comprising of the following three subtypes: PPARα, PPARγ, and PPARβ/δ.
_____ function in the metabolism of fatty acids to help rid the cell of toxic peroxides and provide other essential metabolic functions.
peroxisomes
(Table 5.5) Would the symptoms associated with linoleic acid deficiency best be described as diverse or specific? Why?
• (Table 5.5) Highly diverse symptoms have been found in linoleic acid deficiency because of its central role in two processes that broadly impact cellular function. They are 1) cell membrane properties that affect membrane-bound protein complexes and receptors in all tissues and 2) formation of the dominant eicosanoid precursors, GLA and AA.
what intervention for: classic essential fatty acid deficiency
- corn or safflower oil
- fish oil, avoid hydrogenated oils
- good quality fats and oils
- n3 PUFAs, (use n PUFAs with caution)
good quality fats and oils
what intervention for: linoleic acid insufficiency
- corn or safflower oil
- fish oil, avoid hydrogenated oils
- good quality fats and oils
- n3 PUFAs, (use n PUFAs with caution)
corn or safflower oil
what intervention for: long chain PUFA dependent neuromembrane function.
- corn or safflower oil
- fish oil, avoid hydrogenated oils
- good quality fats and oils
- n3 PUFAs, (use n PUFAs with caution)
fish oil, avoid hydrogenated oils
what intervention for: low stearic to oleic ratio.
- corn or safflower oil
- fish oil, avoid hydrogenated oils
- good quality fats and oils
- n3 PUFAs, (use n PUFAs with caution)
n3 PUFAs, (use n PUFAs with caution)
what intervention for:low GLA and DGLA
- flax, primrose, or black current oils
- Primrose
- restrict booze, add lecithin, increase Met
- Vitamin e, and C, Se Mn, Zn
primrose
Fatty liver: what intervention for: saturated and Omega-9 (greek w-9) accumulation in the liver
pg 294
- flax, primrose, or black current oils
- Primrose
- restrict booze, add lecithin, increase Met
- Vitamin e, and C, Se Mn, Zn
restrict booze, add lecithin, increase Met
what intervention for:high PUFA intake without antioxidants
- flax, primrose, or black current oils
- Primrose
- restrict booze, add lecithin, increase Met
- Vitamin e, and C, Se Mn, Zn
Vitamin e, and C, Se Mn, Zn
what intervention for: Alpha or gamma linolenic acid insufficiency
- flax, primrose, or black current oils
- Primrose
- restrict booze, add lecithin, increase Met
- Vitamin e, and C, Se Mn, Zn
flax, primrose, or black current oils
(CI 5.1) Describe the fatty acid profile imbalance that tends to exaggerate inflammatory responses?
- Generally low levels of n-6 PUFAs, and especially EPA along with elevated AA.
- Generally low levels of n-3 PUFAs, and especially DHA along with elevated AA.
- Generally low levels of n-6 PUFAs, and especially EPA along with elevated ALA.
- Generally low levels of n-3 PUFAs, and especially EPA along with elevated AA.
generally low levels of n-3 PUFAs, and especially EPA along with elevated AA.
