General Flashcards
(109 cards)
1
Q
Type I familial dyslipidemia - Hyperchylomicronemia
A
AR
Defect in Lipoprotein lipase or altered apo-C-II (co-factor for lipoprotein lipase)
Causes: creamy layer in supernatant. pancreatitis, HSM, eruptive/pruritic xanthomas *NO increase risk for atherosclerosis
2
Q
Type IIa familial dyslipidemia - Familial hypercholesterolemia
A
AD
Defective or absent LDL receptor (binds apoB100)
Increased LDL and cholesterol (~300 in heterozygotes, ~700 in homozygotes)
Causes accelerated atherosclerosis-> early cardiovascular disease, Tendon xanthomas, xanthelesmas (eyelid cholesterol deposits), corneal arcus
3
Q
Type III familial dysbetalipoprotienemia
A
Defect in Apo E (decreased remnant reputake by liver) -> VLDL and chylomicrons accumulate
Increased levels of cholesterol and TG
Causes premature cardiovascular disease and xanthomas
4
Q
Type IV- familial hypertriglyceridemia
A
AD
Defective Apo A-V, Hepatic overproduction of VLDL
Causes hyptertriglyceridemia >1000 and increases risk for acute pancreatitis
5
Q
Alkaptonuria
A
AR defect in homogentisic acid (HGA) oxidase, prevents degradation of phenylalanine and tyrosine to fumarate -> HGA accumulates which is pigmented black/blue
Findings: Dark connective tissue Brown sclera Urine turns black on standing Debilitating arthralgias (HGA build up in cartilage)
6
Q
Leucine zipper
A
Dimerization domain found in transcription factors
Made up of 30 amino acid alpha helical fragments that have leucine at every 7th position
7
Q
Carbamoyl phosphate synthase I and II
A
CPS I:
Urea cycle- 1st step
Mitochondira
converts NH3, CO2 and 2ATP -> carbamoyl phosphate
CPSII:
Pyrimidine synthesis- 1st step
Cytoplasm
Converts Glutamine+CO2+2ATP -> carbamoyl phosphate
8
Q
Chronic granulomatous disease
A
Defective NADPH -> inefficient PMN oxidative burst -> increased risk of infection from encapsulated gram + organisms
9
Q
Nonpolar (hydrophobic) amino acids
A
glycine, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline
10
Q
Adenosine deaminase (ADA) deficiency
A
AR
Cannot break down adenosine -> ATP and dATP excess imbalances nucleotide pool via feed back inhibition of ribonucleotide reductase -> prevents DNA synthesis -> decreased lymphocyte count
One major cause of SCID
11
Q
Lesch-Nyhan syndrome
A
XR absent HGPRT (converts hypoxanthine to IMP and guanine to GMP) -> defective purine salvage -> excess uric acid and de novo purine synthesis
Findings:
- Hyperuricemia -> gout
- Aggression, self-mutilation
- Retardation
- Dystonia
Treatment: allopurinol or febuxostat (inhibit XO -> decrease uric acid buildup)
12
Q
DNA polymerase I
A
Degrades RNA primer and replaces with DNA
13
Q
DNA polymerase III
A
Elongates strand 5’->3’ synthesis
Proofreads with 3’->5’ exonuclease
14
Q
What disease is caused by defective single strand nucleotide excision repair?
A
Xeroderma pigmentosum -> prevents repair of pyrimidine dimers from UV exposure
15
Q
What disease is caused by defective DNA mismatch repair?
A
Hereditary nonpolyposis colorectal cancer (HNPCC)
16
Q
What disease is caused by defective double strand nonhomologous end joining to repair double-stranded breaks?
A
Ataxia telangiectasia (ATM mutation) - nonhomologous end joining required VDJ recombination -> immunodeficiency
Fanconi anemia
17
Q
CDKs
A
Promote cell division, constitutive and inactive
18
Q
Cyclins
A
Regulatory proteins that control cell cycle; phase specific; Activate CDKs
19
Q
Cyclin-CDK complex
A
phosphorylates other proteins like Rb to coordinate cell cycle progression
20
Q
Rb
A
Tumor suppressor gene
Rb loses phosphate group after mitosis; when hypophosphorylated -> inhibits G1-S progression
Is activated by being phosphorylated by CDK -> G1-> S progression
If both Rb genes mutated-> causes unrestrained cell division
21
Q
p53
A
If there is DNA damage p53 prevents progression of G1->S and stimulates repair enzymes. If DNA is repaired the cell can resume G1->S, if not repaired then apoptosis
2 hit mutation -> unrestricted cell division (Li-Fraumeni syndrome)
22
Q
Where are steroids synthesized?
A
Smooth ER, also site of drug and poison detox and site of G6Pase (last step of gluconeogenesis)
23
Q
Drugs that act on microtubules
A
Mebendazole (anti-helminthic) Griseofulvin (antifungal) Colchicine (antigout) Vincristine/Vinblastine (anticancer) Paclitaxel (anticancer)
24
Q
What cell type does vimentin stain for?
A
connective tissue
25
What cell type does desmin stain for?
muscle
26
What cell type does cytokeratin stain for?
epithelial cells
27
What cell type does GFAP stain for?
neuroglia
28
What cell type does neurofilaments stain for?
neurons
29
What is composed of type I collagen?
Most common
(Decreased in osteogenesis imperfecta)
```
Bone
Skin
Tendon
Dentin
Fascia
Cornea
Late wound repair
```
30
What is composed of type II collagen?
Cartilage (including hyaline), vitreous body, nucleus pulposus
31
What is composed of type III collagen?
Reticulin- skin, blood vessels, uterus, fetal tissue, granulation tissue
Deficient in vascular type of Ehlers-Danlos syndrome
32
What is composed of type IV collagen?
Basement membrane, basal lamina, lens
Defective in Alport syndrome, targeted by antibodies in Goodpasture syndrome
33
What are the components of collagen?
Gly-X-Y (X and Y are proline or lysine), collagen is 1/3 glycine
34
Which steps of collagen synthesis take place inside the fibroblasts and which take place outside?
Inside fibroblasts:
1. synthesis (RER) - preprocollagen
2. hydroxylation (RER) of proline and lysine (Vitamin C required)
3. glycosylation (RER) - formation of triple helix procollagen
4. exocytosis of procollagen in to extracellular space via COPII
Outside fibroblasts:
5. proteolytic processing- cleave disulfide-rich terminal regions --> tropocollagen (insoluble)
6. Cross-linking of tropocollagen --> collagen fibrils (defective in Ehlers-Danlos and Menkes disease)
35
Ehlers-Danlos
Can be AD or AR
Hyperextensible skin, easy bruising, hypermobile joints (type V collagen mutation)
May be associated w/ berry and aortic aneurysms, organ rupture (type III collagen mutation)
36
Menkes disease
Rare XR disorder caused by defective ATP7A Menkes protein -> impaired copper absorption and transport -> decreased lysyl oxidase (co-factor)
- Brittle 'kinky' hair
- Growth retardation
- hypotonia
- seizures
- decreased muscle tone
- blue sclera
37
Elastin
rich in non-hydroxylated proline, glycine, lysine
Tropoelastin with fibrillin scaffolding (Fibrillin defect in Marfan syndrome)
Broken down by elastase which is inhibited by alpha1-antitrypsin (A1AT deficiency causes emphysema)
Wrinkles -> decreased collagen and elastin production
38
What is identified in Southern, Northern, Western, and Southwestern blots?
Southern blot - DNA
Northern blot - RNA
Western blot - protein
Southwestern blot - DNA-binding proteins (transcription factors)
39
Fragile X syndrome
X-linked defect causing hypermethylation of FMR1 gene -> decreased expression, Trinucleotide repeat of (CGG)n
2nd most common genetic cause of retardation
Large testes, jaw and ears
Autism
MVP
40
Ataxia-telangiectasia
AR, mutation in ATM gene
DNA hypersensitivity to ionizing radiation due to defective DNA repair of double strand non-homologous end joining, which is usually caused by radiation
Features:
- Ataxia from cerebellar atrophy (1st years of life)
- Telangiectasias
- Recurrent sinopulmonary infections (severe immunodeficiency)
- Increased risk of cancer
41
lac operon regulation
High glucose -> decreases adenylate cyclase activity -> low cAMP -> poor binding of CAP to CAP-DNA binding domain -> decreased expression of lac operon genes
Low glucose -> High cAMP -> CAP binds CAP site -> induces transcription
High lactose -> unbinds repressor protein from repressor/operator site -> Increased transcription
Low lactose -> repressor protein is bound to operator -> no transcription
42
Down Syndrome
Trisomy 21 due to nondisjunction (95%), Robertsonian translocation (4%) or mosaicism (1%)
1st trimester
- ultrasound: Increased nuchal translucency and hypoplastic nasal bone
- low serum PAPP-A
- high free beta-hCG
2nd trimester:
- low AFP and estriol
- high beta-hCG and inhibin A
Findings:
Mental retardation
Flat faces, prominent epicanthal folds, single palmar crease
Duodenal atresia
Hirschsprung disease
Congenital heart defects: ASD of ostium primum, cleft in leaflet of mitral valve and tricuspid valve -> regurgitation
Brushfield spots
Associated with:
- Increased risk of ALL and AML
- Early onset Alzheimer disease (amyloid precursor protein on chromosome 21)
43
Edwards syndrome
Trisomy 18
1st trimester: low PAPP-A and beta-hCG
2nd trimester: low AFP, beta-hCG, estriol and low/normal inhibin A
Features shared with Patau:
Severe retardation
Rocker-bottom feet
congenital heart disease
Features distinguished from Patau:
* micrognathia (small jaw)
* low-set ears
* overlapping fingers
* prominent occiput
44
Patau syndrome
Trisomy 13
1st trimester: low hCG and PAPP-A, increased nuchal translucency
Findings shared with Edwards:
Severe retardation
Rocker-bottom feet
Congenital heart disease
Distinguishing features from Edwards syndrome:
* microphthalmia
* microcephaly
* cleft lip/palate
* holoprosencephaly
* polydactyly
* cutis aplasia
45
Pyruvate dehydrogenase deficiency
X-linked
Prevents conversion of pyruvate to acetyl CoA so pyruvate is shunted to alanine (via ALT) and lactic acid (via LDH) -> lactic acidosis
Can be acquired in alcoholics due to vitamin B1 (Thiamine) deficiency which is necessary cofactor for PDH
Findings:
Neuro defects, lactic acidosis, high serum alanine
Treatment: ketogenic diet - Lysine and leucine
46
Prader-Willi syndrome
Maternal imprinting w/ deletion or mutated Paternal gene (on chromosome 15)
-25% of cases due to maternal uniparental disomy (2 maternally imprinted genes received and no paternal gene received)
Features:
- Hyperphagia
- Obesity
- Retardation
- Hypogonadism
- Hypotonia
47
Angelman syndrome
Paternal imprinting w/ deletion or mutation of maternal gene (chromosome 15)
~5% of cases due to paternal uniparental disomy
Features:
- Inappropriate laughter 'happy puppet'
- seizures
- ataxia
- Severe retardation
48
Duchenne muscular dystrophy
X-linked, frameshift mutation in DMD gene -> shortened dystrophin protein -> inhibited muscle regeneration; dystrophin helps anchor muscle fibers to ECM
Features: onset
49
Becker muscular dystrophy
X-linked, non-frameshift insertion in dystrophin gene -> partially functional
Less severe than Duchenne, presents in adolescence or early adulthood
50
Myotonic type 1 muscular dystrophy
AD CTG trinucleotide repeat in DMPK gene -> abnormal expression of myotonin protein kinase
Features:
- Myotonia
- Muscle wasting
- Cataracts
- Testicular atrophy
- Frontal balding
- Arrhythmia
51
Cri-du-chat syndrome
Microdeletion of short arm of chromosome 5 (5p-)
Findings:
- microcephaly
- retardation
- high-pitched crying (mewing)
- cardiac abnormalities- VSD
- epicanthal folds
52
Williams syndrome
microdeletion of long arm of chromosome 7 (includes elastin gene)
Findings:
'Elfin' facies
Intellecutal disability
Hypercalcemia (increase vitamin D sensitivity)
Well-developed verbal skills
Extreme friendliness
Aortic stenosis (cardiovascular problems)
Diagnose w/ FISH
53
mitochondrial myopathies
MERRF (myoclonic epilepsy with ragged red fibers) -> EM shows increased number of enlarged abnormally shaped mitochondria
MELAS- mitochondrial encephalopathy w/ stroke-like episodes and lactic acidosis
Leber optic neuropathy (blindness)
54
What is produced by the HMP shunt (pentose phosphate pathway) and what is it used for?
Provides NADPH and ribose from abundant glucose6P
NADPH is necessary for reductive reactions:
- glutathione reduction in RBCs
- fatty acid and cholesterol biosynthesis
Ribose is necessary for nucleotide synthesis and glycolytic intermediates
Sites: lactating mammary glands, liver, adrenal cortex (sites of FA or steroid synthesis), RBCs
55
What are the reactions involved in the HMP shunt?
Oxidative (irreversible), rate limiting step
enzyme: Glucose-6P dehydrogenase
NADP+ + Glucose6P ---> CO2 + 2 NADPH + Ribulose-5-P
Nonoxidative (reversible),
enzymes: phosphopentose isomerase, transketolases
Ribulose-5-P Ribose5P + Glucose3P + Fructose6P
56
Glucose-6P dehydrogenase deficiency
X-linked recessive; more prevalent among blacks, increased malarial resistance
Causes deficiency in NADPH, which is necessary for glutathione reduction -> detoxes free radicals and peroxidase
low NADPH -> hemolytic anemia (Heinz bodies and bite cells) due to decreased RBC defense against oxidizing agents and/or stress:
- Fava beans
- Sulfonamides
- Primaquine
- Isoniazid
- Infection
57
Hexokinase vs glucokinase
phosphorylation of glucose to give glucose-6-P, first step in glycolysis
Location:
hexokinase -most tissues
Glucokinase- liver and pancreas beta cells
Km:
Hexokinase Km glucokinase
Vmax (capacity):
Hexokinase
58
How is fructose-2,6-BP regulated by glucagon and insulin?
FBPase-2 converts fructose-2,6BP into fructose 6P (toward gluconeogenesis)
PFK-2 converts fructose-2,6BP into fructose-1,6-BP (toward glycolysis)
Fasting state: Increase glucagon -> increase cAMP -> increase protein kinase A (PKA) -> (+) FBPase2, (-) PFK-2 -> gluconeogenesis
Fed state: Increase insulin -> low cAMP -> decrease PKA -> (-) FBPase2, (+) PFK-2 -> glycolysis
59
Co-factors required for pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex
1. pyrophosphate (B1, thiamine, TPP)
2. FAD (B2, riboflavin)
3. NAD (B3, niacin)
4. CoA (B5, pantothenic acid)
5. Lipoic acid
PDH complex activated by exercise which:
Increases NAD+/NADH ratio
Increases ADP
Increases Ca2+
60
TCA cycle: irreversible enzymes
OAA + Acetyl-CoA --citrate synthase--> citrate
Isocitrate ---isocitrate DH--> alpha-KG + CO2 + NADH
alpha-KG --alphaKG DH--> succinyl CoA + CO2 + NADH
61
What reaction in the TCA cycle produces GTP?
succinyl-CoA -> succinate + GTP + CoA
62
What are the toxins that affect the electron transport chain?
Cause a decrease in H+ gradient and block of ATP synthesis
Rotenone ---| Complex I (NADH dehydrogenase)
Antimycin A ----| Complex III (cytochrome complex)
Cyanide, CO ---| Complex IV (cytochrome oxidase)
63
What toxin inhibits ATP synthase?
Causes an increase in H+ gradient and block of ATP synthesis
Oligomycin ---| Complex V (ATP synthase)
64
Pyruvate carboxylase
In mitochondria, Pyruvate --> OAA
Requires biotin B7, ATP
(+) acetyl-CoA
65
Phosphoenolpyruvate carboxykinase (PEPCK)
cytosol; OAA --> PEP
Requires GTP
66
Fructose-1,6-bisphosphatase
Cytosol; F-1,6-BP --> F-6-P
(+) citrate
(-) F-2,6-BP
67
Glucose-6-phosphatase
ER; glucose-6-P ---> gluocse
68
How can fatty acids contribute to gluconeogenesis?
Odd-chain FAs -> propinoyl-CoA can enter TCA as succinyl-CoA --> gluconeogenesis
Even-chain FAs cannot produce new glucose since yield only acetyl-CoA equivalents
69
Where does gluconeogenesis occur?
Primarily liver, enzymes also in kidney, intestinal epithelium
--> deficiency of key enzymes cause hypoglycemia since muscle cannot contribute due to lack of glucose 6 phosphatase
70
What occurs when oxidative phosphorylation is uncoupled? What can cause uncoupling?
Increase permeability of membrane -> low H+ gradient and high O2 consumption; ATP synthesis stops but e- transport continues
Produces heat
Caused by:
2,4-dinitrophenol (used illegally for weight loss)
aspirin (fevers after OD)
thermogenin (brown fat)
71
Essential fructosuria
AR defect in fructokinase
Benign, asymptomatic, since fructose not trapped in cells
Symptoms: fructose in blood and urine
72
Fructose intolerance
AR deficiency of aldolase B
Fructose1P builds up causing low available phosphate --| glycogenolysis and gluconeogenesis
Symptoms following consumption of fructose (fruit, honey etc):
- hypoglycemia
- jaundice
- cirrhosis
- vomiting
- UA (-) since only tests for glucose, reducing sugar can be detected
Treatment: restrict consumption of fructose and sucrose (glucose + fructose)
73
Galactokinase deficiency
AR deficiency of galactokinase
galactitol galactose1P
Galactitol accumulates if galactose in diet; relatively mild condition
Symptoms:
- galactose in blood and urine
- infantile cataracts
- may have failure to track objects or develop social smile
74
Classic galactosemia
AR ABSENCE of GALT (galactose-1-phosphate uridyltransferase)
Galactose1P ---x--> glucose 1P
Accumulation of galactose1P AND galactitol
```
Symptoms:
failure to thrive
jaundice, HSM
infantile cataracts
intellectual disability
```
Treatment: exclude galactose and lactose from diet
75
Hyperammonemia
Can be acquired (liver disease) or hereditary
Causes excess NH4+ -> depletes alphaKG --| TCA
```
Symptoms:
tremor (asterixis)
slurred speech
somnolence
vomiting
cerebral edema
blurry vision
```
Treatment:
- Limit protein in diet
- Lactulose to acidify GI tract and trap NH4+ for excretion
- Rifaximin to decrease ammoniagenic bacteria
- Benzoate or phenylbutyrate to excrete AAs
76
N-acetylglutamate synthase deficiency
Required cofactor for carbamoyl phosphate synthetase I
77
Kozak sequence
Role in initiation of translation-> binding mRNA molecule to ribosomes
purine (G or A) positioned 3 bases upstream from AUG is key factor
Mutation replacing guanine (G) with cytosine (C) in beta-globin gene at this position is associated with thalassemia intermedia
78
Ornithine transcarbamylase deficiency (OTC)
X-linked recessive (other urea cycle enzyme deficiencies are AR)
Presents: usually in first few days of life, but may present later
Excess carbamoyl phosphate -> orotic acid -> orotic acid builds up in blood and urine --> decreased BUN, symptoms of hyperammonemia (tremor, slurring, vomiting etc)
NO megaloblastic anemia (seen in orotic aciduria)
79
Phenylketonuria (PKU)
AR; Deficiency of phenylalanine hydroxylase or tetrahydrobiopetrin (BH4)
Phenylalanine --x--> tyrosine
Tyrosine becomes essential and phenylalanine builds up -> increased phenylketones in urine
Findings:
- intellectual disability
- growth retardation
- seizures
- fair skin
- eczema
- musty body odor (from phenylketones)
Treatment: diet with tyrosine supplementation and restriction of phenylalanine (artificial sweetners), BH4 supplementation
Maternal PKU -> infant findings: microcephaly, intellecutal disability, growth retardation, heart defects
80
Maple syrup urine disease
AR; Deficiency of branched chain alpha-ketoacid dehydrogenase (B1 co-factor) prevents degradation of branched AA -
isoleucine, leucine, valine build up
-increased alpha-ketoacids in blood
Features:
- CNS defects, intellectual disability
- death
Treatment: restrict branch chain AAs in diet, supplement thiamine B1
81
What enzyme deficiency causes albinism?
tyrosinase: DOPA --x--> melanin
82
What are the types of homocystinuria and what are the associated findings?
All AR and all cause excess homocysteine
Methionine cystathionine ---> cysteine
1. Cystathionine synthase deficiency
- Treatment: less methionine, increase cysteine, B12 and folate in diet
2. Decreased affinity of cystathionine synthase for pyridoxal phosphate (B6)
- Treatment: increase B6 and cysteine in diet
3. Homocysteine methyltransferase (methionine synthase) deficiency
- Treatment: increase methionine in diet
```
Findings:
Homocystinuria
intellectual disability
osteoporsis
marfanoid habitus
kyphosis
lens subluxation
thrombosis and atherosclerosis
```
83
Cystinuria
AR defect of renal PCT and intestinal amino acid transporter -> prevents reabsorption of Cysteine, Ornithine, Lysine and Arginine (COLA)
Findings:
cystine stones (hexagonal)
urinary cyanide-nitroprusside test (+)
Treatment:
urinary alkalinization cleaves disulfide bond (potassium citrate, acetazolamide)
chelating agents (penicillamine)
hydration
84
How is glycogen regulated by insulin
High blood glucose -> (+) insulin
- > binds tyrosine kinase receptor (liver and muscle)--> activates protein phosphatase which removes phosphate group:
- > activates glycogen synthase (glucose -> glycogen)
- > inhibits glycogen phosphorylase (inactive when phosphate removed) glycogen -x-> glucose
Overall --> increased glycogen, decreased glycogenolysis
85
How does glucagon regulate glycogen metabolism?
low blood glucose -> (+) glucagon -> binds glucagon receptor in liver -> activates AC -> increase cAMP -> activate protein kinase A -> activates glycogen phosphorylase kinase -> phosphorylation of:
- glycogen phosporylase (activates)-> increase glycogenolysis
- glycogen synthase (inactivates) -> decreased glycogen formation
Overall --> increased glucose, decreased glycogen
86
glycogen metabolism in skeletal muscle
Glycogen undergoes glycogenolysis -> glucose 1 phosphate -> glucose6P which is metabolized during exercise (g6P cannot leave cell)
87
Glycogen metabolism in hepatocytes
Glycogen stored and undergoes glycogenolysis to maintain blood sugar levels
1. Glycogen phosphorylase frees glucose1P residues off branched glycogen until 4 glucose units remain (called limit dextrin)
2. glucanotransferase (debranching enzyme)
3. alpha-1,6-glucosidase (debranching enzyme) cleaves last residue -> release glucose
88
fatty acid synthesis
Mostly takes place in cytosol, of liver, adipose, lactating mammary glands
1. mitochondrial matrix: citrate goes through citrate shuttle to pass through mitochondiral membrane
2. cytoplasm: citrate --ATP citrate lyase--> Acetyl-CoA
3. cytoplasm: rate limiting step Acetyl CoA + CO2 (from biotin) --acetyl CoA carboxylation--> malonyl-CoA
4. cytoplasm
malonyl-CoA + NADPH
--Fatty acid synthase--> palmitate --> fatty acid synthesis
89
Fatty acid degredation
beta oxidation, takes place mostly in mitochondria
1. Cytosol
FA + CoA --FA CoA synthase--> FA-CoA
2. FA-CoA enters carnitine shuttle to pass through mitochondrial membrane into mitochondrial matrix
3. Mitochondria: beta oxidation
FA-CoA --Acyl CoA dehydrogenases--> Acyl CoA
4. Acyl CoA --> ketone bodies or TCA cycle
90
Medium- chain acyl-CoA dehydrogenase deficiency
AR disorder of FA oxidation
Decreased ability to break down fatty acids into acetyl-CoA -->
- accumulation of 8-10C fatty acyl carnitines in blood
- hypoketotic hypoglycemia
Presentation:
- infancy or early childhood
- vomiting
- lethargy
- seizures
- coma
- liver dysfunction
Treat: avoid fasting
91
What occurs in the fed state (right after meal)
Glycolysis and aerobic respiration
Insulin -> (+) storage of lipids, proteins and glycogen
92
What occurs during fasting (between meals)
Hepatic glycogenolysis (major)
Hepatic gluconeogenesis
Adipose release of free FA (minor)
Glucagon and epinephrine stimulate use of fuel reserves
93
What occurs in starvation of 1-3 days?
Glycogen reserves deplete after day 1?
Blood glucose levels maintained:
- Hepatic glycogenolysis
- Adipose release of FFA
- muscle and liver start using FFAs
- Hepatic gluconeogenesis from peripheral tissue (lactate and alanine) and from adipose tissue (glycerol and propionly CoA only TAG components that contribute to gluconeogenesis)
94
What occurs in starvation after day 3?
Adipose stores used (ketone bodies become main source of energy for brain)
After adipose stores depleted -> vital protein degradation accelerates -> organ failure and death
Excess adipose determines survival time
95
HMG-CoA reductase
rate-limiting step in cholesterol synthesis
HMG-CoA --> mevalonate
(+) insulin, (-) statins
96
LCAT
catalyzes cholesterol esterification so that it can be stored
97
Lipoprotein lipase
LPL, degrades TGs circulating in chylomicrons and VLDLs
Found on vascular endothelial surface, adipose and muscle cells
98
Hepatic TG lipase
Degradation of TGs remaining in IDL
99
Hormone-sensitive lipase
degradation of TGs stored in adipocytes
100
Function of ApoE
mediates remnant uptake in liver
Found on chylomicron, chylomicron remnant, VLDL, IDL, HDL
101
Function of ApoA-I
activates LCAT
Found on Chylomicron and HDL
102
Function of ApoC-II
Lipoprotein lipase co-factor
Found on chylomicron, VLDL and HDL
103
Function of ApoB-48
Mediates chylomicron secretion from intestine into lacetals
Found on chylomicron, chylomicron remnant
104
Function of ApoB100
Binds LDL receptor, synthesized in liver
Found on VLDL, IDL, LDL
105
Chylomicron
Highest % TGs and lowest % protein; lowest density
Secreted by intestinal epithelial cells (ApoB48)
Delivers dietary TGs to peripheral tissue
Delivers cholesterol to liver via chylomicron remnant (most TG depleted)
106
VLDL
Secreted by liver. Delivers hepatic TGs to peripheral tissue
107
IDL
Formed in degradation of VLDL, delivers TGs and cholesterol to liver
108
LDL
No ApoE
Formed by hepatic lipase modification of IDL in peripheral tissue.
Delivers hepatic cholesterol to peripheral tissue.
Taken up via receptor-mediated endocytosis (ApoB-100)
109
HDL
Highest density, Highest%protein, lowest%TG
- Secreted from liver and intestine.
- Mediates cholesterol transport from periphery to liver
- Acts as repository for apoC and E (needed for chylomicron and VLDL metabolism)
- Can be repackaged as VLDL or used for bile salts
Alcohol increases synthesis
