SM02 Mini4 Flashcards Preview

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Flashcards in SM02 Mini4 Deck (215):
1

what class of hormones has the shortest half life?

small peptides

2

what are the substrates for prostaglandin synthesis and which is most abundant?

eicosatrienoic acid

arachidonic acid **most abundant**

eicosapentaenoic acid

3

where does the arachidonic acid for prostaglandin synthesis come from?

phosphoglycerates in cell membranes

4

how is arachidonic acid releases from membranes?

by hydration via phospholipase A2

5

what is the first stable prostaglandin product? describe how it is synthesized.

PGH2

  • arachidonic acid is oxygenated by 2 O2 molecules via cyclooxygenase
  • forms PGG2
  • PGG2 dehydrated by peroxidase
    • assisted by 2 glutathione (converted to GSSG)

6

what are the basic structural units of prostaglandins?

20 carbons

a carboxyl group

a ring (usually 5 membered)

7

what does the subscript in the name of a prostaglandin indicate?

the number of double bonds it has outside of the ring structure

8

prostaglandins with one double bond are made form which fatty acid?

eicosatrienoic acid

9

prostaglandins with two double bond are made form which fatty acid?

arachidonic acid

10

prostaglandins with three double bond are made form which fatty acid?

eicosapentaenoic acid

11

where is COX-1 found?

constitutively in most tissues

12

where is COX-2 found?

mainly in leukocytes

inducible in some other tissues

13

function of TXA2

platelet aggregation

inflammation

14

function of PGE2

vasodilaton

uterine contraction

inflammation

fever

reduced gastric acid secretion & enhaced mucus formation→ protective for stomach mucosa

15

functions of PGI2

vasodilation

16

function of PGF2alpha

uterine contractions

17

what prostaglandins are used to induce an abortion?

PGE2 & PGF2alpha

18

what are the disadvantages to using prostaglandins as pharmacologic agents?

  • rapidly metabolized
  • affect multiple organ systems⇒ many side effects

19

what is the major structural difference between the prostaglandins and leukotrienes?

no ring structure in leukotrienes

20

what adds variety to the leukotriene family?

LTC4 contains bound glutathione

amino acids of glutathione may be cleaved to create a different leukotriene

21

describe the lipoxygenase pathway

  • 5-LOX acts on arachidonic acid w/O2
  • creates 5-HPETE
  • rearranges to LTA4
  • addition of glutathione creates LTC4​​

22

how do leukotrienes contribute to asthma pathology?

cause bronchoconstriction

23

what class of drugs inhibit phospholipase A2?

anti-inflammatory steroids

ex. glucocorticoids

24

what is the direct consequence of phospholipase A2 inhibition?

reduced formation of prostaglandins & leukotrienes

25

what common drugs selectively inhibits COX-1?

ASA

26

what is the direct effect of inhibiting COX enzymes?

prevent synthesis of prostaglandins, BUT NOT leukotrienes

  • reduce: inflammation, pain, fever, platelet aggregation and thrombus formation
  • increase likelihood of gastric complaint & bronchoconstriction in asthma pts

27

what is the most abundant hormone found in blood plasma?

cortisol

300nmol/L

28

which concentration level determines a hormones biological effect?

concentration of free hormone

not total

29

what are hormone plasma levels dependent on?

  • rate of hormone secretion
  • amount of hormone bound to plasma proteins
  • rate at which hormone is metabolized or excreted

30

how does protein binding effect hormones?

protects hormone from enzymatic breakdown & renal excretion

31

which hormone levels can be tested?

total, free, and bound hormone levels

as well as levels of binding protein

32

how does binding protein deficiency affect hormone activity?

it doesn't→pt should be healthy

hormone activity is completed by free hormone

only total hormone plasma levels will be decreased

33

what is used to measure hormone levels and why?

antibodies for their high level of sensitivity and specificity

b/c hormone levels are normally found in very low overall plasma concentrations

34

what type of testing is used to detect hormone levels?

ELISA: radioimmunoassay or sandwich

35

what are the major protein hormones?

GH, prolactin

36

what are the major glycoprotein hormones?

LH

FSH

TSH

37

what are the major peptide hormones?

ACTH

oxytocin

vasopressin

endorphins

38

what are the neurohypophysial hormones?

aka posterior pituitary

oxytocin & ADH/vasopressin

39

what is the function of oxytocin?

uterine conctractions during childbirth

milk ejection

40

what is the function of ADH?

aka antidiuretic hormone or vasopressin

anitdiuresis

vasoconstriction at higher concentrations (during hypovolemia)

41

what is the function of TSH?

aka thyrotropin

to stimulated the thyroid to produce & release hormone

42

what are the hormones produced in the anterior pituitary?

aka adenohypophysis

TSH

LH

FSH

ACTH (adrenocorticotropic hormone)

GH

prolactin

43

where are the hormones of the posterior pituitary synthesized?

neurosecretory neurons of the hypothalamus

only stored in the neurohypophysis

44

how are the neurosecretory hormones made?

prohormones attached to larger neurophysin

neurophysin I attached to oxytocin

neurophysin II attached to vasopressin

45

which hormones are initially synthesized as proopiomelanocortin (POMC)?

ACTH & MSH

in the corticotrophs of the anterior pituitary gland

also lipotropin (beta & alpha: involved in adipocyte breakdown) & beta-endorphins

 

46

where are the steroid hormones produced?

mainly in specialized endocrin glands

ex. testosterone in testes or ovaries

47

what types of hormones utilize nuclear receptors?

steroid hormones

thyroid hormones

retinoic acid (vitamin A)

calcitriol (vitamin D)

dietary lipids

48

what is the function of the thyroid hormones?

increase metabolic rate & have important developmental effects

49

what is the structural building block of the thyroid hormones?

tyrosine

50

how is insulin synthesized?

  • in pancreatic beta cells
  • preproinsulin synthesized in rER
  • signal sequence is removed while ribosome is still synthesizing polypepetide
  • tertiary structure forms spontaneously
  • disulfide bonds form between alpha & beta chains
  • endopeptidase cuts out C-peptide
    • no known function

51

why do many labs test for C-peptide instead of insulin?

  • released in equimolar amounts
  • C-peptide survives longer than insulin in the blood→ at higher level
  • can be used in pts that use insulin injections to measure endogenous insulin levels
    • diabetic patients

52

describe the angiotension synthesis.

  • angiotensinogen converted to angiotensin I by renin (from kidneys)
  • angiotensin I converted to angiotensin II by converting enzyme (in lung capillaries)

53

where & when is renin secreted?

by the juxtaglomerular cells in the kidneys when intraglomerular pressure is too low

54

how does angiotensin II increase blood pressure?

constricts blood vessels

potentiating effects of norepinephrine on vascular tone

releases aldosterone from adrenal cortex

55

allele frequency

likelihood of encountering the allele in the locus

measured as a fraction of 1 or less frquently as a % 

**sum of allele frequencies for a given locus is 1.**

56

what alleles are more likely to case a single gene disorder?

rare alleles

57

In a swamp area in Nigeria, a newborn screening program tested 100 newborns for the sickle cell mutation. Of these 100 newborns, one was an SS homozygote, and 18 were SA heterozygotes. What is the frequency of the sickle cell allele in this population? 

total of 200 alleles (2 x 100 newborns)

homozygote has 2 S alleles & 18 heterozygotes
each have 1 S allele

20 out of 200 alleles are S alleles. Allele frequency is 0.1
(10%).
 

58

With an allele frequency of 5% for the X-linked recessive color blindness gene, what proportion of women are expected to be color blind? Assume there is no skewed X inactivation.
 

Only women w/mutation on both X chromosomes
are color blind

chance of one mutated X chromosome= 1/20 (5%) 

chance of second mutated X chromosome is
also 1/20

chance of homozygosity= 1/20 x 1/20 = 1/400 (0.25%)

59

what is the allelic frequency for rare autosomal diseases?

1/2 of disease frequency

60

what is the allelic frequency of X-linked diseases?

disease frequency in males

61

what is the allelic frequency of autosomal recessive disorders?

square root of disease frequency

62

conditions for Hardy-Weinberg Equilibrium

  1.  large population
    • reduction of chance effects
  2. no change in allele frequencies through mutation or selection
  3. random mating

63

examples of assortive mating

  • positively: like attracts like
    • dwarves
    • deaf community
  • negatively: opposites attract
    • higher genetic variation in those of mixed races

64

what is the Founder effect?

aka genetic drift

chance event that leads to a high prevalence of a mutation in an originally small population

inbreeding make it more prevalent than it otherwise would be in a larger or communicative population

65

what is consanguinity?

inbreeding

mating between relatives

type of positive assortative mating

66

how much genetic similarity is found among relatives?

  • 1st degree (parents & siblings): 50%
  • 2nd degree (aunt/uncle & grandparents): 25%
  • 3rd degree (first cousins): 12.5%

67

what is autozygosity?

runs of homosygosity that are inherited from long-forgotten shared ancestors

3-8% of genome in most modern populations

68

define genetic fitness.

measure of extent of selection

fraction of offspring produced by mutation carriers relative to general population

69

what is the fitness of a genetically leathal mutation?

0

70

what type of phenotypes are favored by stabilizing selection?

average phenotypes

ex. birth weight, bp, blood glucose

71

what is the rariest form of selection for quantitative traits?

disruptive selection

average is selected against

72

what is selected for in directional selection?

one side of the bell curve

thus a shift of the curve is seen over time

73

how common is Duchenne muscular dystrophy?

1/4000-1/6000 males

74

cause of DMD

lack of dystrophin protein

75

age of onset of DMD symptoms?

before 5yo

76

what is the probability that a male with DMD is a carrier?

1

b/c it is an x-linked recessive disorder

77

what is the probability that a sister of a DMD male is a carrier?

1/2

78

what is the probability of the sister of a DMD male for showing symptoms if she is a proven carrier?

10% for DMD

only 5% for other x-linked recessive disorders

79

why do some female carriers of an X-linked recessive disorder display symptoms?

skewed X inactivation

80

when are redundant X chromosomes inactivated in females?

late blastula stage of embryonic development

≈2,000-10,000 cells

81

how are X chromosomes inactivated?

  • copies of X-inactivation center (XIC) transiently align
  • XIST (X inactivation-specific transcript) [non coding mRNA] and its antisense transcript TSIX get upregulated on one chromosome & downregulated on the other
  • on upregulated chromosome, XIST RNA covers chromosome
  • initiates X inactivation
  • after downstream events, XIST expression no longer needed 

82

what are the downstream events caused by XIST coverage?

  • DNA methylation
  • histone modifications
  • accumulation of variant histone
  • asynchronus replication
  • RNA polymerase II exclusion

83

if the diseased X chromosome also carries a balanced translocation, what is the probability of displaying symptoms?

she will express disease

b/c loss of translocated chromosome lead to cell death if diseased chromosome were inactivated

84

what are pseudoautosomal regions?

identical regions found on X & Y chromosomes

PAR1 is on p arm & PAR2 is on q arm

85

presentation of DMD

Duchenne's muscular dystrophy

  • normal developmental milestones until 2yo
  • more clumsy
  • difficulty jumpin or climbing stairs
  • muscle weakness from proximal to distal & lower before upper limbs
  • Gower's sign around 5-6yo
  • inability to walk 10-12yo
  • death @ 16-20yo
    • due to heart or lung muscular failure

86

function of dystrophin

large protein associated w/sarcolemma

involved in linking extracellular laminin w/intracellular thin filaments

87

difference in cause of DMD v. BMD

  • DMD
    • deletion causes reading frame disruption
    • dystrophin protein is absent
  • BMD (Becker's Muscular Dystrophy)
    • deletion conserves reading frame of gene
    • dystrophin is present but usually of abnormal size

88

how is DMD diagnosed?

  • increased creatine kinase 
    • sign of muscle degradation
  • leads to DNA PCR test
    • not all 70 known mutations are tested for only most common
  • if negative, confirm w/muscle biopsy for dystrophin detection
  • if dystrophin absent, follow up to detect specific mutation
    • look for female carriers in family

89

cause of limb girdle muscular dystrophy

mutations of large number of genes 

LGMD1 is autosomal dominant

LGMD2 is recessive

90

what is the likelihood that a new mutation has caused in isolated cause of X-linked DMD?

1/3

91

what is the risk that a sister to an isolated DMD case would be a carrier?

1/3

92

what is the risk that a sister to an isolated DMD case would give birth to an affected child?

1/6

93

22-yo male; father w/Huntington's dz. healthy in his forties, what is his risk taht he has the disease-causing allele?

autosomal dominant, full penetrance

1/2 chance of having dz allele

1/2 chance of having dz allele & no clinical signs at 40yo

(1/2 x 1/2)

divided by his total risk of being dz free: (1/2 x 1/2) + 1/2 (no dz allele)

1/3

94

penetrance

probability of getting dz in question if you have dz allele

quoted as probability of proportion

95

variable expressivity

those w/dz allele that show varying signs of dz

96

Woman's father had autosomal dominant childhood dz w/0.9 penetrance. She was healthy. What is the likelihood that her child will have the dz? 

1/2 chance of having non-dz allele

1/10 chance of having dz allele w/no clinical dz

(1/2 x 1/10)/[(1/2 x 1/10) + 1/2] = 1/20 / 11/20 = 1/11

1/11  chance of mother having dz allele

1/11 x 1/2= 1/22 chance of child having dz allele x 0.9 (penetrance)= 0.04 chance of child having dz

97

A woman has an son w/an isolated case of DMD and a healthy son. what is the risk that her next child will have DMD?

DMD is X-linked recessive w/1/3 of cases arising from new mutations

2/3 chance that mother is carrier of dz

1/2 chance of boy having dz

(2/3 x 1/2)/[(2/3 x 1/2) + 1/3] = 1/3 / 2/3 = 1/2

98

predictive value

with + test, the likelihoood that pt actually has dz

99

specificity

probability of negative given that pt is known to not have dz

proportion of non-dz w/negative test

100

how can a clinical exam help with the probability of a test?

clinical examination for signs & symptoms increases prior probability

which increases the positive predictive value by only performing the test on those who are likely to have dz

101

recurrance risk is equal to?

square of population disease frequency

102

what is the difference between polygenic & multifactorial?

polygenic: many genes

multifactorial: many genes and environmental factors (food, vitamins, toxins, light, radiation, etc)

103

how are multifactorial dz risks calculated?

called empirical recurrence risk

only empirically additive

more dz alleles→ increased risk for dz

threshold # of dz alleles for dz development

104

what is the empirical recurrence risk for a multifactorial dz?

2-5%

105

how does the risk change as relationship distance increases?

1st degree (parents & siblings)→ 2-5%

2nd degree (aunt/uncle & nephew/niece)→half of 1st degree (1-2.5%)

3rd degree (cousin & great-grandchild)→ normal population risk

106

what type of inheritance does pyloric stenosis display?

multifactorial

higher incidence in boys than girls

107

what type of inheritance do neural tube defects display?

multifactorial

polygenic

and can be reduced by half by folic acid supplementation

108

what factors can increase the empirical recurrence risk of disease?

more serious condition

if affected child is of the less often affected gender

with each affected child, recurrence increases for subsequent children

109

for what types of genetic diseases does environment play a larger role?

polygenic

the more genes involved the more important the role of the environment is in determining the development of disease

110

hologenome

evolution of not just the human genome, but the complex of the human & the microbiome that lives in and on us

111

what types of studies can be used to investigate multifactorial diseases?

adoption

twin

association

genome wide association

"next gen sequencing"

112

what are the possible causes of a congenital condition?

intrauterine infection

maternal drug use

spontaneous (Dr. speak for "I don't know')

chromosomal abberation

autosomal recessive

autosomal dominant (one parent should have)

X-linked recessive

multifactorial (usually only causes single malformation)

113

what is a set of clinical findings that have a common non-genetic cause?

sequence

114

why would two very tall people have a son that isn't as tall?

b/c multifactorial traits regress toward the mean

this is a statistical phenomenon

115

heritability

proportion of total variance that is attributable to genetic factors

correlation calculated between relatives

given as a figure between 0 and 1

116

why does heritability appear to change in different societies?

change in environmental factors, can be reduced or increased

117

how can environmental factors influence best be studied?

adoption studies or monoztgotic twins that were adopted is even better

similar genetics in different environments

118

how is an association study designed?

  • find people w/dz
  • find people w/o dz
  • check both groups for a number of markers
  • some markers are found more frequently in those w/dz
  • look for dz allele in chromosomal area where these markers are found

119

what are the multifactorial imposters?

syndrome that include a sign or symptom of interest but usually come with other effects as well

120

for a certian marker w/2 alleles, 99.9% of alleles in the population are type A, the other allele being denoted a. Would this marker be a good candidate for a marker in a linkage study?

NO

very few people in the population would be heterozygous & thus potentially more informative

121

confounders in a linkage study

  • crossing over/recombination
  • uninformative markers
  • phenocopies: look the same, but different gene
  • reduced penetrance/variable expressivity
  • non-paternity
  • missing information: family member is unkown dz status (died early of something else or losts touch)

122

how likely or unlikely is it that 2 pieces of one chromosome end up on different chromosomes after recombination?

theta

recombination fraction

if theta is small, then very unlikely to be separated by crossing over

if large (cannot be larger than 0.5), rather likely to end up on different chromosomes after crossing over

123

how often will a marker and an allele with no linkage end up together by chance alone?

50%

this is why theta cannot exceed 0.50

124

markers & alleles that go together in a family

linkage eqilibrium 

125

markers & alleles that go together in the population

linkage disequilibrium

126

repulsion

marker and dz allele are on different DNA strands

127

coupling

marker & dz allele on same DNA strand

128

how is a linkage study set up?

  • identify family w/dz
  • identify phenotype of dz
    • #1 for confusion & confounding factors
  • calculate statistical power
  • genotyping
  • linkage analysis: finds chromosomal area 
  • sequence gene found
  • validate mutations found

129

power

probability of rejecting null hypothesis when alternative hypothesis is actually true

130

null hypothesis

the markers is inherited independently of the gene associated w/dz

131

logarithm of the odds

Z (zeta)

log (data given linkage/data given if no linkage)

if LOD>/=3, significant evidence for linkage

if = -2, evidence of no linkage

132

as a trinucleotide repeat gets longer over the generations, what is likely to occur in the phenotype of the disease?

earlier onset

133

when histones are acetylated, chromatin...?

chromatin is open for transcription factor binding

134

normal function of polyglutamines

enhance protein-protein interactions, often between transcription factors

when expanded in dz, can lead to protein aggregates & sequestration of transcription factors

135

signs & symptoms of Huntington's dz

onset 30-55yo

worsens over 10-20yrs til death

  • twitching
  • chorea
  • dementia

136

cause of Huntington's Dz

  • repeat expansion of CAG-repeats
    • premuatation >30 repeats
    • >36 in affected
  • huntingtin protein normally sequesters repressor transcription factor in cytoplasm; mutated protein does not→ BDNF  transcription is reduced
  • also used for BDNF vesicle transport→ mutant binds too tightly reducing BDNF transport

137

what is the difference between a type I & type II repeat disease?

  • type I
    • CAG trinucleotide repeat
    • glutamine 
    • exceeds 35 repeats
    • affects the brain
  • type II
    • variety of trinucleotides
    • does not code for glutamine
    • repeats over 200
    • affects numerous parts of the body

138

signs & symptoms of Fragile X Syndrome

mental retardation

macroorchidism

large ears

prominent jaw

high-pitched jocular speech

autistic-like features

139

where is the genetic mutation in Fragile X Syndrome?

5'UTR of familial mental retardation gene

200-2000 repeats of CGG

hypermethylation of DNA in & around CGG tract→ shuts off promotor→ no protein produced

140

what occurs with 55-200 repeats in the 5'UTR of FMR-1?

Fragile X tremor ataxia syndrome

predominantly in older males

ataxic gait, intention tremor, & cognitive impairment

141

Fagile X Syndrome premutation-related disorders

primary ovarian insufficiency in women

gait ataxia

frontla lobe dementia

142

normal function of FMRP protein

binds RNA molecules & regulates their translation by controlling their stability & release to the polyribosome

in dz, protein synthesis is exaggerated, internalization of AMPA receptors, long-term depression exaggeration

143

genetic cause of dystrophia myotonia

type I: expansion of CTG in 3'UTR

OR

type II: CCTG repeat in intron 1

of different genes

144

signs & symptoms of dystophia myotonia

  • progressive muscle wasting & weakness in 20/30s
  • myotonia: stiffness & tighness of muscles
    • slow relaxation of certain muscles
  • cataracts
  • cardiac conduction defects
  • balding & infertility in men
  • breathing problems, developmental delays, & death in babies

145

most common autosomal recessive ataxia

Friedreich ataxia

146

genetic cause of Friedreich ataxia

GAA repeat expansion in 1st intron of grataxin gene

200-1000+ repeats

147

function of frataxin

mitochondrial protein involved in iron homeostasis, especially Fe-S complex synthesis & heme synthesis

lack causes: electron transport chain inefficiency, excess free radicals, low ATP production, mitochondrial iron overload, & loss of myelinated axons in peripheral nerves

148

define genomic imprinting

process of differently marking chromosomal regions during gametogenesis

causes parental alleles to be differentially expressed in tissues of offspring

silencing of non-working copy of a gene by addition of methyl and/or acetyl groups to DNA or histones

149

mechanisms fo imprinting regulation

CTCF-dependent insulators

long noncoding RNA (antisense RNA)

150

what causes the formation of an ovarian teratoma?

26XX karyotype from two female pronuclei

benign tumor

151

what causes a complete hydatidiform mole?

46XX or 46XY karyotype from paternal only→ empty oocyte fertilized by 2 X sperm OR 1 sperm undergoes endoreplication

causes hyperplasia of trophoblast

may lead to choriocarinoma

no fetus develops

152

what causes a partial hydatidiform mole?

69 chromosomes

dispermy of normal oovum

fetus is always present, but rarely survives to term

153

what happens to the fetus when mother's Igf2R gene is deleted and father's igf2 gene is deleted?

normally sized offspring

154

what happens to the fetus when mother's Igf2R gene is deleted and father's igf2 gene is present?

Beckwith Wiedeman Syndrome

overly large offspring

congenital malformations

predisposition to embryonic neoplasia

155

what happens to the fetus when mother's Igf2R gene is present and father's igf2 gene is deleted?

Russell Silver Syndrome

dwarf offspring: slow growth & low birthweight

abnormal head growth: triangular

thin, short

curving of 5th finger

asymmetric growth of some body parts

digestive abnormalities

increased risk of delayed development & learning disabilities

156

cause of Prader-Willi Syndrome

partial deletion of paternal chromosome 15

lack of expression of SNRNP (controls gene splicing for brain proteins)

157

signs & symptoms of Prader-Willi Syndrome

reduced motor function

obesity

mental deficiencies

158

cause of Angelman Syndrome

partial deletion of maternal chromosome 15

lack of expression of UBE3A (involved in ubiquination)

159

signs & symptoms of Angelman Syndrome

hyperactivity

unusual seizures

repetitive muscle movements

mental deficiencies

160

transcriptional effect of DNA methylation

gene repression

161

transcriptional effect of histone acetylation

gene activation

162

transcriptional effect of histone deacetylation

gene repression

163

conversion of pyvruvate to glucose

gluconeogenesis

164

conversion of glucose to ribose

pentose phosphate pathway

165

what substances stimulate gluconeogenesis?

glucagon

epinephrine

glucocorticoids

166

what inhibits gluconeogenesis?

insulin

167

where does gluconeogenesis occur?

mainly the liver

but also renal cortex & skeletal muscle

168

what enzyme for gluconeogenesis is only found in the liver & why?

glucose 6-phosphatase

removes phosphate group from G6P to produce glucose

if it were in other tissues, glucose would be lost

liver does this to maintain blood glucose levels

renal cortex & skeletal muscle that undergo gluconeogenesis, do not have this enzyme b/c they will used G6P to make their own ATP, not for release

169

what enzymes are in gluconeogenesis, but not glycolysis?

pyruvate carboxylase

PEP-carboxykinase

fructose 1,6-bisphosphatase

glucose 6-phosphatase

170

describe the Cori cycle.

  • erythrocytes lack mitochondria
  • use glucose for glycolysis & release lactate into plasma (gains 2 ATP)
  • lactate enters liver
  • liver uses lactate in gluconeogenesis to produce glucose (uses 6 ATP)

171

Why would muscle tissue release alanine into plasma instead of lactate?

to help elminate ammonia 

172

how is PEP carboxykinase regulated?

PEP=phosphoenolpyruvate

inhibited by insulin

activated by glucagon & cortisol

173

how is pyruvate carboxylase regulated?

inhibited by ADP (cell can't afford to release glucose)

activated by acetyl-CoA

 

174

how is fructose 1,6-bisphosphatase regulated?

inhibited by insulin

activated by glucagon, NE, & epi

activated by ATP & citrate

competitively inhibited by fructose 2,6-bisphosphate (activates PFK-1 in glycolysis)

175

how is glucose 6-phosphatase regulated?

inhibited by insulin

stimluated by glucagon

inhibited by glucose (don't need to make more if you have in excess)

176

enzymes of fructose metabolism

  • fructokinase
    • fructose→ fructose 1-phophate
  • aldolase B
    • forms DHAP & glyceraldehyde
  • triokinase
    • glyceraldehyde→ glyceraldehyde 3-phosphate

177

what is the rate limiting step in fructose metabolism?

Aldolase B

formation of DHAP & glyceraldehyde

178

why is high dietary fructose bad?

  • fructose 1-phosphate accumulates→ phosphate trapping→ low energy (no phosphate for ATP)
  • fructose bypasses PFK-1 regulation in glycolysis→ accumulation of lactate & triglycerides

179

defect of fructokinase results in?

benign fructosuria

180

defect of Aldolase B results in?

hereditary fructose intolerance

  • poor feeding
  • failure to thrive
  • hepatic & renal insufficiency
  • death
  • asymptomatic if fructose & sucrose are avoided in diet

181

defect or deficiency of fructose 1,6-bisphophatase results in?

hereditary fructose intolerance like condition

182

enzymes of galactose metabolism

galactokinase

galatose 1-phosphate uridyl-transferase

UDP-galactose 4-epimerase

183

cause of galatosemia

autosomal recessive inheritance pattern

deficiency of galactose-phosphate uridyl-transferase

184

features of galactosemia

  • cannot convert galactose to glucose
  • elevated AST & ALT in newborns
  • mental deficiency & cirrhosis
  • galactitol accumulation in lens→ cataracts

185

what are the cellular needs for NADPH?

  • reduction of NTP (nuceltide triphosphates) to deoxy-NTPs for DNA synthesis
  • fatty acid & steroid biosynthesis
  • oxidant control in erythrocytes

186

why does partial deficiency of glucose 6-phosphate dehydrogenase cayse RBC hemolysis?

no NADPH

no glutathione recovery

build up od peroxide

187

where is fructose synthesized?

polyol pathway takes place in seminal vesicles

fructose is found in seminal fluid

  • aldose reductase
    • glucose→ sorbitol
  • sorbitol dehydrogenase
    • sorbitol→ fructose

188

glycogen is polymerized glucose build on what substrate?

glycogenin protein

189

function of glycogen phosphorylase a

remove glucose 1-phosphate form glycogen

190

how is glycogen phosphorylase a regulated?

  • inactivated by increased protein phosphatase-1
    • increased by insulin
  • activated by increased phosphorylase kinase 
    • increased by increased protein kinase A
    • increased by glucagon
  • inhibited by presence of 
    • glucose
    • glucose 6-phophate
    • ATP
  • stimulated by presence of Ca2+ & AMP in muscle

191

how does increased protein kinase A affect glycogen synthase a?

inactivates it

192

what activates glycogen synthase b to glycogen synthase a?

increased protein phosphatase-1

193

how does increased insulin lead to glycogen synthase activation?

  1. increases protein phosphatase-1→ activates glycogen synthase
  2. leads to protein kinase B activation→ inhibits glycogen synthase kinase-3 that normally inactivates glycogen synthase

194

classes of steroid hormones

  • progestins
  • glucocorticoids
  • mineralocorticoids
  • estrogens
  • androgens

195

where are the steroid hormones produced?

adrenal cortex

gonads

placenta

196

how do the steroid hormones exert their effects?

since they are derived from cholesterol & thus lipid soluble→ pass freely thru cell membranes

act on transcription factors

197

what is the function of desmolase?

converstion of cholesterol to pregnenolone

198

what is the function of StAR protein?

aka steroidogenic acute regulator

regulation for conversion of cholesterol into pregnenolone

since desmolase is located inside the inner mitochondrial membrane, StAR transports cholesterol to it

199

how are steroid hydroxylations performed?

steroid-H + O2 + HADPH + H+ → Steroid-OH + NADP+ + H2O

via cytochrome P450

200

how are androgens & estrogens transported in the blood?

sex-hormone binding globulin

201

transcortin is a transport protein for?

glucocorticoids

202

how is testosterone synthesized from cholesterol?

  • cholesterol→pregnenolone by desmolase
  • pregnenolone→ progesterone by 3beta-HSD
  • progesterone→ testosterone by 17alpha-hydroxylase & C17,20 lyase

203

how is estradiol made?

from testosterone via aromatase

204

how is cortisol synthesized?

from pregnenolone

  1. 17alpha-hydroxylse converts to 17alpha OH-pregnenolone
  2. 3beta-HSD converts to 17alpha OH-progesterone
    • thus can also be made from progesterone via enzyme in 1
  3. 21alpha-hydroxylase converts to 11-deoxycortisol
  4. 11beta-hydroxylase converts to cortisol

205

how is aldosterone synthesized?

from pregnenolone

  1. 3beta-HSD converts to progesterone
  2. 21alpha-hysdroxylase converts to 11-deoxycorticosterone
  3. 11beta-hydroxylase converts to corticosterone
  4. aldosterone synthase converts to aldosterone

206

cause of Cushing's syndrome

excess glucocorticoids

207

cause of Cushing's disease

 ACTH-secreting pituitary tumor

causing excess glucocorticoids

208

how does licorice cause HTN?

component of licorice root inhibits oxidation of cortisol to inactive form, cortisone

build up for cortisol

209

cause of congential adrenal hyperplasia

  • 21alpha-hydroxylase deficiency
  • 11beta-hydrolyase deficiency
  • reduced corticosteroids
  • elevated ACTH

210

effects of congenital adrenal hyperplasia

  • overproduction of adrenal androgens
    • continuous due to no cortisol production for - feedback on pituitary
  • Na+ wasting→ hyperkalemia→ peaked T waves & widened QRS
  • ambiguous genitalia in females & early puberty in males

211

effect of 5alpha-reductase deficiency

ambiguous genitalia at birth

virilization at puberty→ "penis at 12" syndrome (autosomal recessive)

212

most common cause of Cushing syndrome

iatrogenic

overuse of antiinflammatory steroids

213

features of Cushing's syndrome

truncal obesity

loss of fat from extremities

weak connective tissue→ striae (stretch marks)

secondary diabetes mellitus type II

214

how is cortisol inactivated?

by 11-hydroxysteroid dehydrogenase to cortisone

NAD dependent rxn

occurs in liver

215

how can 21alpha-hydroxylase deficiency & 11beta-hydroxylase deficiency be differentiated since they both cause virilization

21→ hyperkalemia, salt wasting/craving

11→ hypokalemia, salt sparing→HTN