MTC Exam III part V

Question 1

hPL

Answer 1

human placental lactogen
secreted by the placenta
promotes lactation, growth, and production of corpus luteum
inhibits maternal insulin

Question 2

Type II diabetes diagnostic criteria

Answer 2

1. fasting glucose >126 mg/dl
2. symptoms and plasma glucose >200
3. plasma glucose >200 2 hrs after a 75g oral glucose ingestion
4. hemoblobin A1C > 6.5%

Question 3

When are the fetus’ needs for energy highest (trimester wise_

Answer 3

3rd trimester

Question 4

caudal regression syndrome

Answer 4

syndrome in infants born to diabetic moms. characterized by hypoplasia of sacrum and lower extremities.

Question 5

type I, IIa, and IIx muscle fibers

Answer 5

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

Question 6

concentric, eccentric, isometric constractions

Answer 6

concentric: shortening of a muscle against resistance
eccentric: controlled lengthening of a muscle
isometric: muscle contractions without a change in muscle length

Question 7

NRF1/2

Answer 7

nuclear response factor. help mediate inc. in mitochondria in endurance training.

Question 8

EGR-1

Answer 8

upregulates COX genes during response to endurance training

Question 9

PGC1a

Answer 9

important in endurance training
controls PPARs. PPARs increase expression of genes for lipid trafficking, beta oxidation, uncoupling of electron transport chain, mitofusion

Question 10

How is PGC1a regulated

Answer 10

increased by increased Ca++, by AMPK, and by DNA demethylation upon acute exercise

Question 11

IGF-1

Answer 11

factor that increases protein synthesis through the mTOR pathway during resistance training

Question 12

PGC1a4

Answer 12

splice variant of PGC1a that is active and important during resistance training. helps regulate myostatin and IGF1.

Question 13

EF2

Answer 13

important in protein synthesis: resistance training

Question 14

ACE alleles for perfomance enhancement

Answer 14

I vs. D. I has an insertion and is seen in endurance atheletes; D better for resistance/power athletes

Question 15

ACTN3: performance enhancement

Answer 15

577R vs. 577X. RR better at resistance; XX better at endurance. ACTN3 mostly seen in fast twitch fibers

Question 16

MSTN

Answer 16

leads to muscle hypertrophy when inhibited/knocked out.

Question 17

equation that estimates mutation rate

Answer 17

m=I X S
I = incidence
S = selectivity
S = 1 means that this trait causes a total loss of reproductive activity.

Question 18

equation for the genetic difference between human populations

Answer 18

(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.

Question 19

What is the difference btw RDA and adequate intake, nutritionally speaking?

Answer 19

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.

Question 20

What is the estimated average requirement for a given nutrient?

Answer 20

EAR is the avg. daily nutrient intake level at which inadequacy is seen in 50% of the population

Question 21

What are the functions of vitamin A, and what are the three forms I should know?

Answer 21

Retinol: storage form; retinal: visual pigment; retinoic acid: hormone
Functions: mediate vision, fat-soluable anti-oxidant, helps with development

Question 22

What happens in vitamin A toxicity?

Answer 22

increased skin pigmentation, increased lung cancer risk, liver damage, possible birth defects

Question 23

How is vitamin A absorbed and stored?

Answer 23

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.

Question 24

Vitamen C: what are the main functions? How can it be absorbed

Answer 24

antioxidant, regenerates vitamin E and protects LDL from oxidation. It is critical for collagen synthesis. Absorbed from fresh fruits: not very stable

Question 25

scurvy symptoms and causes

Answer 25

cause: not enough vitamin C
symptoms: bleeding gums, impaired wound healing, easy bleeding/bruising, joint and bone pain, vision problems

Question 26

Vitamin E functions

Answer 26

lipid peroxidation, inhibition of atherosclerotic plaque formation,

Question 27

What happens if you have vit E deficiency? Toxicity?

Answer 27

deficiency: neuropathy and sensory problems
toxicity: hemorrhagic stroke

Question 28

What two organs synthesize heme? For what two proteins do we need it most?

Answer 28

bone marrow and liver

needed for hemoglobin and for cytochrome P450s (detox)

Question 29

How is heme synthesis controlled in the liver?

Answer 29

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.

Question 30

acute intermittent porphyria:

inheritance pattern, symptoms, biochem

Answer 30

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.

Question 31

Porphyria cutanea tarda. biochem, symptoms,

Answer 31

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)

Question 32

How is heme degraded?

Answer 32

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.

Question 33

What enzyme is responsible for conjugating bilirubin?

Answer 33

bilirubin glucuronyltransferase or UDP glucuronyltransferase (same enzyme, 2 names) adds 2 UDPs to bilirubin in a 2 step process

Question 34

What can be measured in a bilirubin blood test?

Answer 34

Direct bilirubin measures conjugated/soluable bilirubin.
total measures total
unconjucated/indirect bilirubin is measured as total-direct

Question 35

hemolysis and hyperbilirubinemia

Answer 35

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.

Question 36

Gilbert’s syndrome

Answer 36

unconjugated hyperbilirubinemia caused by impaired hepatic uptake of bilirubin

Question 37

Crigler-Najjar syndrome

Answer 37

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.

Question 38

Benign Neonatal Jaundice

Answer 38

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.

Question 39

Conjugated hyperbilirubinemias

Answer 39

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

Question 40

Dubin Johnson Syndrome

Answer 40

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.

Question 41

What factors regulate calcium levels? What is released when Ca is low vs when it is high?

Answer 41

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.

Question 42

symptoms of hypocalcemia

Answer 42

paresthesia (“pins and needles”), muscle spasms, cardiac arrhythmia, osteoporosis, increased QT interval

Question 43

What are two likely pathological causes of hypercalcemia?

Answer 43

excess PTH/parathyroid issues or cancer

Question 44

hypercalcemia symptoms

Answer 44

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

Question 45

What regulates Phosphorus and how?

Answer 45

parathyroid hormone and vitamin D.
PTH increases renal phosphorus excretion- lowers phosphorus.
Vitamin D increases P absorption: increases P.

Question 46

hypophosphatemia

Answer 46

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.

Question 47

hyperphosphatemia

Answer 47

increases in metastatic calcicfication that can cause tissue and organ damage. usually caused by laxatives, diabetic ketoacidosis, vitamin D toxicity, or low PTH

Question 48

rickets: cause

Answer 48

vitamin D deficiency

Question 49

pharmacokinetics vs. pharmacodynamics

Answer 49

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.

Question 50

P450 CYP family

Answer 50

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

Question 51

N-Acetylation (NAT). examples of the significance of NAT polymorphisms?

Answer 51

-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

Question 52

Thiopurine S-methyltransferase. Significance?

Answer 52

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.