MTC Exam III part V Flashcards
hPL
human placental lactogen
secreted by the placenta
promotes lactation, growth, and production of corpus luteum
inhibits maternal insulin
Type II diabetes diagnostic criteria
- fasting glucose >126 mg/dl
- symptoms and plasma glucose >200
- plasma glucose >200 2 hrs after a 75g oral glucose ingestion
- hemoblobin A1C > 6.5%
When are the fetus’ needs for energy highest (trimester wise_
3rd trimester
caudal regression syndrome
syndrome in infants born to diabetic moms. characterized by hypoplasia of sacrum and lower extremities.
type I, IIa, and IIx muscle fibers
type I: red muscle/slow twich. lots of mitochondria, lots of capillaries, resistant to fatigue, uses fat oxidation for energy
IIa: intermediate. also fast twitch but has a moderate amt of mitochondria and can use fat or glucose
type IIx: fast twich/white muscle. few atp; uses glycolysis for ATP production
concentric, eccentric, isometric constractions
concentric: shortening of a muscle against resistance
eccentric: controlled lengthening of a muscle
isometric: muscle contractions without a change in muscle length
NRF1/2
nuclear response factor. help mediate inc. in mitochondria in endurance training.
EGR-1
upregulates COX genes during response to endurance training
PGC1a
important in endurance training
controls PPARs. PPARs increase expression of genes for lipid trafficking, beta oxidation, uncoupling of electron transport chain, mitofusion
How is PGC1a regulated
increased by increased Ca++, by AMPK, and by DNA demethylation upon acute exercise
IGF-1
factor that increases protein synthesis through the mTOR pathway during resistance training
PGC1a4
splice variant of PGC1a that is active and important during resistance training. helps regulate myostatin and IGF1.
EF2
important in protein synthesis: resistance training
ACE alleles for perfomance enhancement
I vs. D. I has an insertion and is seen in endurance atheletes; D better for resistance/power athletes
ACTN3: performance enhancement
577R vs. 577X. RR better at resistance; XX better at endurance. ACTN3 mostly seen in fast twitch fibers
MSTN
leads to muscle hypertrophy when inhibited/knocked out.
equation that estimates mutation rate
m=I X S
I = incidence
S = selectivity
S = 1 means that this trait causes a total loss of reproductive activity.
equation for the genetic difference between human populations
(pi-pj)^2/ (Pa(1-Pa))
pi and pj are the allelic freqs. of the considered allele in populations i and j.
Pa is the avgs allel among all pops.
What is the difference btw RDA and adequate intake, nutritionally speaking?
RDA is more quantitative. the RDA is the avs daily dietarty nutrient intake level sufficient to meet the nutrient needs of about 98% of the population of a particular age and gender.
When this data doesn’t exist, we look at how much of this nutrient is being taken in by a group of “healthy” people and say that this amount must be adequate.
What is the estimated average requirement for a given nutrient?
EAR is the avg. daily nutrient intake level at which inadequacy is seen in 50% of the population
What are the functions of vitamin A, and what are the three forms I should know?
Retinol: storage form; retinal: visual pigment; retinoic acid: hormone
Functions: mediate vision, fat-soluable anti-oxidant, helps with development
What happens in vitamin A toxicity?
increased skin pigmentation, increased lung cancer risk, liver damage, possible birth defects
How is vitamin A absorbed and stored?
Retinal transferred to the liver a s retinol ester. It is bound to a retinol binding protein. It can then be oxidzed to retinoic acid in a process that requires a zinc cofactor.
Vitamen C: what are the main functions? How can it be absorbed
antioxidant, regenerates vitamin E and protects LDL from oxidation. It is critical for collagen synthesis. Absorbed from fresh fruits: not very stable
scurvy symptoms and causes
cause: not enough vitamin C
symptoms: bleeding gums, impaired wound healing, easy bleeding/bruising, joint and bone pain, vision problems
Vitamin E functions
lipid peroxidation, inhibition of atherosclerotic plaque formation,
What happens if you have vit E deficiency? Toxicity?
deficiency: neuropathy and sensory problems
toxicity: hemorrhagic stroke
What two organs synthesize heme? For what two proteins do we need it most?
bone marrow and liver
needed for hemoglobin and for cytochrome P450s (detox)
How is heme synthesis controlled in the liver?
it is dependent on the pre-existing heme conc.
Extra heme is converted to hemin (Fe3+ form)
hemin decreases the transcription of ALA synthase, which is the enzyme that catalyzes the rate-limiting step of porphyrin synthesis.
If we need to detox a bunch of drugs or toxins or something, we will use up lots of heme in cytochrome p450 synthesis. hemin conc. will decrease and ALA synthase will increase.
acute intermittent porphyria:
inheritance pattern, symptoms, biochem
Autosomal dominant but only has 10% penetrance: must be triggered by something.
Deficiency in porphobilinogen deaminase (PBG deaminase). Normally this is ok- the other allele makes enough enzyme that you don’t notice this. But if P450 needs skyrocket for some reason, you suddenly don’t have enough PBG deaminase to meet needs and there is a build up of toxic intermediates like aminolevulinc acid and porphobilinogen.
symptoms: neurological symptoms, abdominal pain, tachycardia, hypertension, fever, confusion, hallucination, seizures, psychiatric crises. DON’T MISTAKE FOR ACUTE ABDOMEN: barbituate administration can further increase P450 demand and lead to patient death.
Porphyria cutanea tarda. biochem, symptoms,
Enzyme: uroporphyrinogen enzyme deficiency
Again, probably needs to be triggered to see symptoms.
Intermediates form superoxides which cause blistering skin lesions upon exposure to UV light.
Triggers: alcoholism, hormones, iron overload, Hepatitis C, HIV (basically, liver damage is bad here)
How is heme degraded?
In spleen, heme is degraded to biliverdin which is converted to bilirubin which travels through the blood bound to albumin. this is called unconjugated bilirubin.
Unconjugated bilirubin is taken up by the liver, where it is converted to conjugated bilirubin with the addtion of UDP groups. Conjugated bilirubin is released with bile into the intestine. In the intestine, it is either absorbed into the blood or converted to urobilinogen and then stercobilin (brown). If absorbed into the blood, it is converted to urobilin in the kidney (yellow). Excretory product colors are based on bilirubin breakdown product colors.
What enzyme is responsible for conjugating bilirubin?
bilirubin glucuronyltransferase or UDP glucuronyltransferase (same enzyme, 2 names) adds 2 UDPs to bilirubin in a 2 step process
What can be measured in a bilirubin blood test?
Direct bilirubin measures conjugated/soluable bilirubin.
total measures total
unconjucated/indirect bilirubin is measured as total-direct
hemolysis and hyperbilirubinemia
hemolysis: more unconjugated bilirubin is produced by the spleen than the liver can handle (like, more than 10X the normal amt). Increases in indirect bilirubin and urobilinogen are observed.
Gilbert’s syndrome
unconjugated hyperbilirubinemia caused by impaired hepatic uptake of bilirubin
Crigler-Najjar syndrome
congenital UDP glucuronyltransferase deficiencies. presents in first hours of life as severe jaundice and will cause death within the first few years of life without a liver transplant. results in unconjugated hyperbilirubinemia.
Benign Neonatal Jaundice
caused by temporarily lower UDP-glucuronyltransferase activity in neonates. This could be a problem- bilirubin can cross the blood brain barrier- but it is easily treated with phototherapy.
Conjugated hyperbilirubinemias
caused by blocks in bile excretion or by liver damage
gallstones can block the bile duct. fortunately, conjugated bilirubin is soluble so the kidneys can excrete the bilirubin even though it can’t get to the intenstines
or, Dubin Johnson Syndrome: bile can be excreted by hepatic cells. Turns the liver black but is generally benign
Dubin Johnson Syndrome
symptoms: black liver
caused by a problem with bile excretion into bile canniliculi. leads to conjugated hyperbilirubinemia but kidneys can handle this load. this condition is considered benign.
What factors regulate calcium levels? What is released when Ca is low vs when it is high?
parathyroid hormone and vitamin D.
PTH is released when Ca is low and causes release of Ca from bone.Increases Ca. Vitamin D causes more Ca absorption by bone. lowers blood Ca.
symptoms of hypocalcemia
paresthesia (“pins and needles”), muscle spasms, cardiac arrhythmia, osteoporosis, increased QT interval
What are two likely pathological causes of hypercalcemia?
excess PTH/parathyroid issues or cancer
hypercalcemia symptoms
dehydration, painful bones, renal stones, abdominal pain, psychiatric disturbances (mnemonic: painful bones, renal stones, abdominal groans, phyche overtones)
also causes bradycardia, heart block, short QT, arrythmias
What regulates Phosphorus and how?
parathyroid hormone and vitamin D.
PTH increases renal phosphorus excretion- lowers phosphorus.
Vitamin D increases P absorption: increases P.
hypophosphatemia
disruption of cell membranes and ATP defects. Usually only seen among alcoholics.
causes muscle weakness, cardiomyopathy, hemolysis.
Can also be very dangerous/lethal in refeeding syndrome: if you fee a starving person too much too fast, they will suddenly mget super active PFK to try to use the glucose and get acute and potentially lethal drop in phosphorus.
hyperphosphatemia
increases in metastatic calcicfication that can cause tissue and organ damage. usually caused by laxatives, diabetic ketoacidosis, vitamin D toxicity, or low PTH
rickets: cause
vitamin D deficiency
pharmacokinetics vs. pharmacodynamics
kinetics: how the body handles a drug- absorption, binding, distribution, metabolism, excretion.
dynamics: how a drug affects its target tissue. caused by differences in receptors at cell surface, diffs in cytoplasmic content, etc.
P450 CYP family
family of proteins that are crucial in Phase I of drug metab.
it is a mixed function oxidase that uses molecular oxygen and NADPH. Allelic polymoriphisms include “fast” and “slow”clusters
N-Acetylation (NAT). examples of the significance of NAT polymorphisms?
-phase II of drug metab: conjugates polar group to the produce of phase I metab
Slow metabolism is recessive; fast is dominant. important for INH drug metab. INH used to treat TB. If you have slow metab, INH doses might lead to effective overdose: peripheral neuropathy
Thiopurine S-methyltransferase. Significance?
TPMT part of phase II metabolism. Inactives some chem agents, like 6-MP and 6-TG.
Fast, slow, and heterozygous (fast is incomplete dominant)
Slow ppl may have extra complications- you are overdosing them.
