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Biochemistry > General > Flashcards

General Flashcards

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

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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

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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

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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

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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)
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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

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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

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8
Q

Chronic granulomatous disease

A

Defective NADPH -> inefficient PMN oxidative burst -> increased risk of infection from encapsulated gram + organisms

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9
Q

Nonpolar (hydrophobic) amino acids

A

glycine, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline

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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

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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)

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12
Q

DNA polymerase I

A

Degrades RNA primer and replaces with DNA

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13
Q

DNA polymerase III

A

Elongates strand 5’->3’ synthesis

Proofreads with 3’->5’ exonuclease

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14
Q

What disease is caused by defective single strand nucleotide excision repair?

A

Xeroderma pigmentosum -> prevents repair of pyrimidine dimers from UV exposure

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15
Q

What disease is caused by defective DNA mismatch repair?

A

Hereditary nonpolyposis colorectal cancer (HNPCC)

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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

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17
Q

CDKs

A

Promote cell division, constitutive and inactive

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18
Q

Cyclins

A

Regulatory proteins that control cell cycle; phase specific; Activate CDKs

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19
Q

Cyclin-CDK complex

A

phosphorylates other proteins like Rb to coordinate cell cycle progression

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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

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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)

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22
Q

Where are steroids synthesized?

A

Smooth ER, also site of drug and poison detox and site of G6Pase (last step of gluconeogenesis)

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23
Q

Drugs that act on microtubules

A 
Mebendazole (anti-helminthic)
Griseofulvin (antifungal)
Colchicine (antigout)
Vincristine/Vinblastine (anticancer)
Paclitaxel (anticancer)
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24
Q

What cell type does vimentin stain for?

A

connective tissue

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25
Q

What cell type does desmin stain for?

A

muscle

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26
Q

What cell type does cytokeratin stain for?

A

epithelial cells

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27
Q

What cell type does GFAP stain for?

A

neuroglia

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28
Q

What cell type does neurofilaments stain for?

A

neurons

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29
Q

What is composed of type I collagen?

A

Most common

(Decreased in osteogenesis imperfecta)

Bone
Skin
Tendon
Dentin
Fascia
Cornea
Late wound repair
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30
Q

What is composed of type II collagen?

A

Cartilage (including hyaline), vitreous body, nucleus pulposus

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31
Q

What is composed of type III collagen?

A

Reticulin- skin, blood vessels, uterus, fetal tissue, granulation tissue

Deficient in vascular type of Ehlers-Danlos syndrome

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32
Q

What is composed of type IV collagen?

A

Basement membrane, basal lamina, lens

Defective in Alport syndrome, targeted by antibodies in Goodpasture syndrome

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33
Q

What are the components of collagen?

A

Gly-X-Y (X and Y are proline or lysine), collagen is 1/3 glycine

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34
Q

Which steps of collagen synthesis take place inside the fibroblasts and which take place outside?

A

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:

  1. proteolytic processing- cleave disulfide-rich terminal regions –> tropocollagen (insoluble)
  2. Cross-linking of tropocollagen –> collagen fibrils (defective in Ehlers-Danlos and Menkes disease)
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35
Q

Ehlers-Danlos

A

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)

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36
Q

Menkes disease

A

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
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37
Q

Elastin

A

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

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38
Q

What is identified in Southern, Northern, Western, and Southwestern blots?

A

Southern blot - DNA
Northern blot - RNA
Western blot - protein
Southwestern blot - DNA-binding proteins (transcription factors)

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39
Q

Fragile X syndrome

A

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

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40
Q

Ataxia-telangiectasia

A

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
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41
Q

lac operon regulation

A

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

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42
Q

Down Syndrome

A

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)
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43
Q

Edwards syndrome

A

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
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44
Q

Patau syndrome

A

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
Q

Pyruvate dehydrogenase deficiency

A

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
Q

Prader-Willi syndrome

A

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
Q

Angelman syndrome

A

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
Q

Duchenne muscular dystrophy

A

X-linked, frameshift mutation in DMD gene -> shortened dystrophin protein -> inhibited muscle regeneration; dystrophin helps anchor muscle fibers to ECM

Features: onset

49
Q

Becker muscular dystrophy

A

X-linked, non-frameshift insertion in dystrophin gene -> partially functional

Less severe than Duchenne, presents in adolescence or early adulthood

50
Q

Myotonic type 1 muscular dystrophy

A

AD CTG trinucleotide repeat in DMPK gene -> abnormal expression of myotonin protein kinase

Features:

  • Myotonia
  • Muscle wasting
  • Cataracts
  • Testicular atrophy
  • Frontal balding
  • Arrhythmia
51
Q

Cri-du-chat syndrome

A

Microdeletion of short arm of chromosome 5 (5p-)

Findings:

  • microcephaly
  • retardation
  • high-pitched crying (mewing)
  • cardiac abnormalities- VSD
  • epicanthal folds
52
Q

Williams syndrome

A

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
Q

mitochondrial myopathies

A

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
Q

What is produced by the HMP shunt (pentose phosphate pathway) and what is it used for?

A

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
Q

What are the reactions involved in the HMP shunt?

A

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
Q

Glucose-6P dehydrogenase deficiency

A

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
Q

Hexokinase vs glucokinase

A

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
Q

How is fructose-2,6-BP regulated by glucagon and insulin?

A

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
Q

Co-factors required for pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex

A
  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
Q

TCA cycle: irreversible enzymes

A

OAA + Acetyl-CoA –citrate synthase–> citrate

Isocitrate —isocitrate DH–> alpha-KG + CO2 + NADH

alpha-KG –alphaKG DH–> succinyl CoA + CO2 + NADH

61
Q

What reaction in the TCA cycle produces GTP?

A

succinyl-CoA -> succinate + GTP + CoA

62
Q

What are the toxins that affect the electron transport chain?

A

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
Q

What toxin inhibits ATP synthase?

A

Causes an increase in H+ gradient and block of ATP synthesis

Oligomycin —| Complex V (ATP synthase)

64
Q

Pyruvate carboxylase

A

In mitochondria, Pyruvate –> OAA

Requires biotin B7, ATP
(+) acetyl-CoA

65
Q

Phosphoenolpyruvate carboxykinase (PEPCK)

A

cytosol; OAA –> PEP

Requires GTP

66
Q

Fructose-1,6-bisphosphatase

A

Cytosol; F-1,6-BP –> F-6-P

(+) citrate
(-) F-2,6-BP

67
Q

Glucose-6-phosphatase

A

ER; glucose-6-P —> gluocse

68
Q

How can fatty acids contribute to gluconeogenesis?

A

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
Q

Where does gluconeogenesis occur?

A

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
Q

What occurs when oxidative phosphorylation is uncoupled? What can cause uncoupling?

A

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
Q

Essential fructosuria

A

AR defect in fructokinase

Benign, asymptomatic, since fructose not trapped in cells

Symptoms: fructose in blood and urine

72
Q

Fructose intolerance

A

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
Q

Galactokinase deficiency

A

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
Q

Classic galactosemia

A

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
Q

Hyperammonemia

A

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
Q

N-acetylglutamate synthase deficiency

A

Required cofactor for carbamoyl phosphate synthetase I

77
Q

Kozak sequence

A

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
Q

Ornithine transcarbamylase deficiency (OTC)

A

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
Q

Phenylketonuria (PKU)

A

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
Q

Maple syrup urine disease

A

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
Q

What enzyme deficiency causes albinism?

A

tyrosinase: DOPA –x–> melanin

82
Q

What are the types of homocystinuria and what are the associated findings?

A

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
Q

Cystinuria

A

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
Q

How is glycogen regulated by insulin

A

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
Q

How does glucagon regulate glycogen metabolism?

A

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
Q

glycogen metabolism in skeletal muscle

A

Glycogen undergoes glycogenolysis -> glucose 1 phosphate -> glucose6P which is metabolized during exercise (g6P cannot leave cell)

87
Q

Glycogen metabolism in hepatocytes

A

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
Q

fatty acid synthesis

A

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
Q

Fatty acid degredation

A

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
Q

Medium- chain acyl-CoA dehydrogenase deficiency

A

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
Q

What occurs in the fed state (right after meal)

A

Glycolysis and aerobic respiration

Insulin -> (+) storage of lipids, proteins and glycogen

92
Q

What occurs during fasting (between meals)

A

Hepatic glycogenolysis (major)
Hepatic gluconeogenesis
Adipose release of free FA (minor)

Glucagon and epinephrine stimulate use of fuel reserves

93
Q

What occurs in starvation of 1-3 days?

A

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
Q

What occurs in starvation after day 3?

A

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
Q

HMG-CoA reductase

A

rate-limiting step in cholesterol synthesis
HMG-CoA –> mevalonate

(+) insulin, (-) statins

96
Q

LCAT

A

catalyzes cholesterol esterification so that it can be stored

97
Q

Lipoprotein lipase

A

LPL, degrades TGs circulating in chylomicrons and VLDLs

Found on vascular endothelial surface, adipose and muscle cells

98
Q

Hepatic TG lipase

A

Degradation of TGs remaining in IDL

99
Q

Hormone-sensitive lipase

A

degradation of TGs stored in adipocytes

100
Q

Function of ApoE

A

mediates remnant uptake in liver

Found on chylomicron, chylomicron remnant, VLDL, IDL, HDL

101
Q

Function of ApoA-I

A

activates LCAT

Found on Chylomicron and HDL

102
Q

Function of ApoC-II

A

Lipoprotein lipase co-factor

Found on chylomicron, VLDL and HDL

103
Q

Function of ApoB-48

A

Mediates chylomicron secretion from intestine into lacetals

Found on chylomicron, chylomicron remnant

104
Q

Function of ApoB100

A

Binds LDL receptor, synthesized in liver

Found on VLDL, IDL, LDL

105
Q

Chylomicron

A

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
Q

VLDL

A

Secreted by liver. Delivers hepatic TGs to peripheral tissue

107
Q

IDL

A

Formed in degradation of VLDL, delivers TGs and cholesterol to liver

108
Q

LDL

A

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
Q

HDL

A

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

Biochemistry (4 decks)

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