Term
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Definition
- Diacylglycerol 3-phosphate
- phosphoglyceride intermediate |
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Term
| location of phosphatidate synthesis |
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Definition
| - ER and outer mito membrane |
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Term
|
Definition
FROM DHAP
1) reduction of DHAP to Glycerol 3-phosphate
2) Addition of 2 Acyl CoA's
From DAG:
Diacylglycerol Kinase = DAG + ATP ->
phosphatidate + ADP |
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Term
| glycerol phosphate acyltransferase |
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Definition
| adds acyl groups from acyl CoA to glycerol 3 phosphate |
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Term
|
Definition
1) + alcohol -> phosphoglyceride
2) Triacylglycerol synthesis |
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Term
|
Definition
LIVER on ER membrane
Triacylglycerol Synthestase Complex
1) phosphatidic acid phosphatase
2) diglyceride acyltransferase |
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Term
| phosphatidic acid phosphatase |
|
Definition
| hydrolyzes phosphatidate to DAG |
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Term
| diglyceride acyltransferase |
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Definition
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Term
| phospholipid synthesis: activated DAG |
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Definition
1) CTP + phosphatidate -> CDP-DAG + 2Pi
2) CDP-DAG + alcohol -> CMP + phospholipid |
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Term
| phospholipids produced by activated DAG pathway |
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Definition
- phosphatidyl inositol
- diphosphatidylglycerol (cardoilipin) |
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Term
| phospholipid synthesis: activated alcohol |
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Definition
1) ATP + alhocol -> phosphoryl alcohol
2) CTP + phosphoryl alcohol ->
2Pi + CDP-Alcohol
3) CDP-Alcohol + DAG ->
phosphatidyl alcohol + CMP |
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Term
|
Definition
- very important phospholipid
- main mode of sythesis = activated alcohol = CDP-choline
- backup mode = methylation of phosphatidylethanolamine |
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Term
| phosphatidylethanolamine methyltransferase |
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Definition
- when not enough dietary choline, liver enzyme used to produce phosphatidyl choline from phosphatidylethanolamine
- uses 3 SAM's as methyl donors (S- Adenosyl methionine) |
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Term
| phosophotidylserine synthesis |
|
Definition
Base Exchange Reaction:
1) phosphatidylcholine + ser ->
phosphatidylserine + choline
2) phosphatidylethanolamine + ser ->
phosphatidylserine + ethanolamine |
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Term
| phospholipids produced by activated alcohol |
|
Definition
- phosphatidylethanolamine
- phosphatidylcholine
- phosphatidylserine, indirectly |
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Term
|
Definition
ceramide
- 18 carbon
- alcohol at C1 and C3
- amino at C2 bound to acyl
- alkene at C4-C5
(sphingosine with an acyl added) |
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Term
|
Definition
palmitoyl CoA + ser + NADPH + H+
+ Acyl CoA + FAD |
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Term
|
Definition
- ceramide substituted at C1 hydroxyl
- component of lipid rafts
- important in signal transduction |
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Term
|
Definition
Sphingolipid with single carbohydrate substitution (Glc or Gal)
- involves UDP-Glc or UDP-Gal |
|
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Term
|
Definition
Sphingolipid with oligosaccharide subsituent
- must have at least one sialic acid = acidic sugar |
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Term
|
Definition
- stepwise addition of UDP-sugar units
- glycosyltransferases determine the sugars added |
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Term
|
Definition
| - ceramide with choline substituent |
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Term
|
Definition
- ceramide + phosphatidylcholine ->
sphingomyelin + DAG |
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Term
| Respiratory Distress Syndrome |
|
Definition
- inability to synthesize a type of phosphatidylcholine found in ECF around alveoli
- needed to prevent lung collapse
- seen in preemies |
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Term
|
Definition
- lack glycosylase to degrade oligosaccharade of ganglioside
- ganglioside-filled lysosomes |
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Term
| Major point of control in Lipid Metabolism |
|
Definition
- phosphatidic acid phosphatase (PAP)
and diacylglycerol kinase
(phosphatidate <-> DAG) |
|
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Term
| Phosphatidic Acid Phosphatidase |
|
Definition
High PAP activity favors DAG and its products:
- TAG
- Phosphatidylthanolamine
- phosphatidylcholine
- phosphatidylserine
Low PAP activity favors phosphatidate and its products:
- Phosphatidylinositol
- Cardiolipin |
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Term
| Allosteric Regulators of PAP |
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Definition
- stimulatory: CDP-DAG and products of activated phosphatidate pathway
- inhibitory: sphingosines |
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Term
|
Definition
|
|
Term
| Product of Stage I of Cholesterol Synthesis |
|
Definition
isopentenyl pyrophosphate
= activated mevalonate |
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Term
| Product of Stage II of Cholesterol Synthesis |
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Definition
|
|
Term
| Product of Stage III of Cholesterol Synthesis |
|
Definition
|
|
Term
| Location of Chol synthesis |
|
Definition
Stage I - cytoplasm
Stages II and III - ER |
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Term
|
Definition
acetoacetyl CoA + acetyl CoA and H2O ->
CoA + 3 HMG-CoA
HMG-CoA Reductase:
3 HMG-CoA + 2NADPH + sH+ ->
2 NADP+ + CoA + Mevalonate
Mevalonate + 3 ATP ->
Isopentenyl Pyrophosphate + CO2 + 3 ADP + Pi |
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Term
| Committed step of Stage I of Chol Synthesis |
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Definition
| HMG-CoA Reductase = formation of mevalonate |
|
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Term
|
Definition
- involves formation of an allylic isopentene carbocation
- Carbocation is attacked by second isopentenyl pyrophosphatase ->
Geranyl pyrophosphate(C10)
- Geranyl carbocation condenses with 3rd isopentenyl pyrophsophate ->
Farnesyl pyrophosphate (C15)
- Farnesyl carbocation condenses reductively with another farnesyl pyrophosphate ->
Squalene (C30) + NADP+ + PPi |
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Term
|
Definition
- Squalene oxidized (O2 + NADPH) to epoxide
- Oxidosqualene Cyclase: results in cyclic lanosterol
- 19 steps later (3 methyls removed, 1 double bond reduced, 1 double bond migrated) -> Cholesterol |
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Term
| site of cholesterol synthesis |
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Definition
- major site: liver
- intestine |
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Term
| regulation of cholesterol synthesis |
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Definition
| - activity of HMG-CoA Reductase (committed step in isopentenyl pyrophosphate synthesis) |
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Term
| regulation of HMG-CoA Reductase transcription |
|
Definition
- SRE: sterol regulatory element = enhancer of gene for HMG-CoA Reductase (cis-element)
- SREBP: activator of SRE's gene (trans-element)
- SCAP: SREBP cleavage-activating protein = cholesterol sensor within the ER membrane
- Insig = anchors SCAP to ER
If Cholesterol from diet drops:
- SCAP no longer binds Chol
- SCAP escorts SREBP to Golgi
- SREB is cleaved twice: 1) removed from SCAP, 2) regulatory domain is freed to act as transcription factor
if Cholesterol from diet rises:
- SCAP binds Chol
- SCAP binds Insig keeping SCAP-SREBP anchored in ER |
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Term
| regulation of HMG-CoA Reductase translation |
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Definition
| inhibited by mevalonate derivatives |
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Term
| reguation of HMG-CoA Reductase degradation |
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Definition
- HMG-CoA Reductase is bipartite: 1) cytoplasmic domain is catalytic, 2) membrane domain is regulatory
- High sterols lead to HMG-CoA Reductase binding Insigs that are associated with ubiquitinating enzymes. This leads to proteasome degradation. |
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Term
| Regulation of HMG-CoA Reductase activity |
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Definition
| - low Energy Charge: AMP-activated protein kinases turn OFF HMG-CoA Reductase |
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Term
|
Definition
- carry Chol and TAG
- involved in cholesterol homeostasis
- core: lipids
- shell: apoproteins |
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Term
| apoprotein function and production |
|
Definition
- solubilize lipids
- targeting lipids
- made by liver and intestine |
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Term
| lipoproteins in order of increasing density |
|
Definition
chylomicron
chylomicron remnant
VLDL
IDL
LDL
HDL
*low density reflects high TAG constitution |
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Term
| carrying TAG/Chol/lipids from intestine |
|
Definition
Chylomicron:
- 90% TAG
- Apo B48 |
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Term
|
Definition
- hydrolyze TAG's (MAG + FA)carried by chylomicrons
- line blods vessels serving tissues that utilize FA's |
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Term
|
Definition
- cholesterol-enriched
- delivers to the liver |
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Term
| Delivery of lipids from liver |
|
Definition
- liver synthesizes TAG and Chol
- packaged in VLDL with Apo B100 and Apo E |
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Term
|
Definition
- lipases on vessels in serving tissue that utilize TAG
- tissues take up FA leaving behind chol-enriched IDL |
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Term
|
Definition
1) 1/2 taken up by liver
2) 1/2 lose more FA's and are converted into LDL |
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Term
|
Definition
- major chol carrier
- core: chol esterified to FA's
- shell: apo B100
- function: delivery Chol to peripheral tissue to suppress their de novo chol synthesis
- primary source of cholesterol for cells outside the liver and intestine |
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Term
|
Definition
- REVERSE CHOLESTEROL TRANSPORT: scavenges chol from macrophages, dying cells, xs cholesterol from membrane turnover
- core: chol esters |
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Term
|
Definition
- liver: delivers scavenged cholesterol for excretion or bile salts
- Chol-synthesizing tissues: used in hormone synthesis and suppresses de novo chol synthesis |
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Term
|
Definition
- Receptor-Mediated Endocytosis:
docking ->
clathrin coated pit ->
coated vesicle ->
endosome (acidification promotes recycling of receptor) ->
lysosome (more acidic, proteins hydrolyzed, cholesterol esters hydrolyzed) ->
unesterified chol released ->
biosynthesis or re-esterified for storage |
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Term
|
Definition
- regulated by SREBP = enhancer
- inhibited by high cholesterol levels |
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Term
| familial hypercholesterolemia |
|
Definition
- nonfunctioning LDL receptor: usually receptor can't transition to closed state, can't recycle back to membrane, degraded within the cell
- xanthomas: nodules of chol in skin and tendons
- foam cells: macrophages engorged on ox LDL, trapped in blood vessels = plaques
- high blood LDL: can't enter liver |
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Term
|
Definition
7 X LA: bind LDL
3 X EFG:
6 X propeller blades: promote LDL release from endosome
glycoprotein-domain: O-linked sugars
keep receptor extended in membrane
Membrane spanning domain
Cytoplasmic Domain: promotes endocytosis |
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Term
| Mechanism of LDL Receptor release of ligand |
|
Definition
2 states:
- Open = in membrane and ready to bind LDL
- Closed = in acidic endosome and ready to release LDL |
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Term
| lipoprotein that protects against atherosclerosis |
|
Definition
HDL
- inhibits foam cell formation by inhibiting oxLDL and taking up chol from macrophages |
|
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Term
| hypercholesterolemia therapies |
|
Definition
1) Liver transplant if homozygous recessive
2) cholestyramine: bind bile salts preventing chol uptake
3) statins: competitive inhibitor of HMG-CoA Reductase = suppress synthesis |
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Term
|
Definition
cholesterol derivative
- polar and detergent
- synthesized in liver, stored in gall bladder
- solubilize dietary lipids: increase exposure to lipases, increase absorption by intestine |
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Term
|
Definition
Progestens (progesterone)
Glucocorticoids (Cortisol)
Mineralocorticoids (Aldosterone)
Androgens (Androstenedioen, Testo)
Estrogens (Estrone, Estradiol) |
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Term
|
Definition
- type of progesten (C21)
- major site of release = corpus luteum
- prepares uterine lining for implantation
- maintains pregnancy
- along with estrogen, regulates menses |
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Term
|
Definition
- C18
- ovary-release
- secondary sex characteristics
- along with progesterone, regulates menses |
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Term
|
Definition
- C21
- Adrenal cortex-released
- stress response
- promote gluconeogenesis and glycogen formation
- promote fat and protein degradation
- inhibit inflammation |
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Term
|
Definition
- C21
- adrenal cortex release
- act on distal tubules
- increase Na+ reabsorption and K+/H+ excretion
- increase blood volume and pressure |
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Term
|
Definition
- C19
- released by testes
- secondary sex characteristics |
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Term
|
Definition
| diffuse through plasma membrane and activate cytoplasmic transcription factors |
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Term
|
Definition
- liver and intestine ER cytochrome
- uses O2 and NADPH to hydroxylate steroids, oxidize toxins for excretion
- NADPH used to reduce Fe3+ to Fe2+ so cytochrome can bind oxygen |
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Term
| carcinogens and cytochrome P450 |
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Definition
| carcinogens are activated by oxidation |
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Term
|
Definition
- precursor to steroid hormones
- C21 = cholesterol minus 6 carbons from tail
- C18 substituent is an acetyl group |
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Term
|
Definition
- calcium and phosphorus metabolism
- processed by the liver and kidneys |
|
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Term
|
Definition
- active Vit D
- 1,23-dihydroxycholecalciferol |
|
|
Term
|
Definition
- childhood Vit D deficiency
- poor calcification of cartilage, bone
- causes: poor sunlight, poor diet |
|
|
Term
|
Definition
- adult Vit D deficiency
- soft/weak bones |
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