lipid metabolism HW

steps/location/O2 requirement for b-oxidation?

4 / mitochondria / aerobic

net reaction for b-oxidation

FA + FAD + NAD+ → Acetyl-Coa + FADH2 + NADH

fate of acetyl coa

local: TCA

global: Ketone bodies

is b-oxidation need state or fed state

need

rate controlling component of b-oxidation

influx of FA-CoA to the mitochondria

steps/location/O2 requirement for FA synthesis?

7 / cytosol / anaerobic

net reaction for FA synthesis

Acetyl-Coa + HCO3- + ATP + NADH → FA + CO2 + ADP + NADP+

what is the fate of FA synth in the liver?

FA → TAG → storage in adipose tissue

is FA synthesis need or fed state

fed

rate controlling component of FA synthesis

ACC (Acetyl-CoA carboxylase)

how do bile acids facilitate the digestion process

they emulsify fat which increases the SA for enzyme degradation

where are bile acids made and stored?

made: liver

stored: gall bladder

what is peristalsis

mechanical movement of the stomach muscles that physically mixes the acids in the stomach

whats the general theme for molecules exiting the GI tract

ONLY monomers exit the GI tract

two roles of FABP

1. increase solubility

2. help facilitated diffusion (FA out > FA in)

what does FABP do on the diagram?

binds black sticks

describe the route of lipids in the blood beginning with chylomicrons

chylomicrons → intestinal lymph → blood → peripheral tissues (size decrease b/c TAGs + Chol. delivered) → cholesterol rich chylomicron remnants → liver uptake by receptor mediated endocytosis

describe the process for uptake of chylomicron remnants and circulation of VLDL particles

remnants (RME) → liver (+ endogenous TAG + cholesterol) → VLDL particles (increase in size b/c + TAG + chol.) → peripheral tissues (decrease in size b/c deliver TAG + chol.)

decribe the pathway FAs must take before it participates in b-oxidation

FA + ATP + CoASH → FA-CoA → FA-carnitine (cyto) → FA-carnitine (mito) → FA-Coa mito

chemistry steps of beta oxidation

oxidation → hydration → oxidation → cleavage

FA FG steps of beta oxidation

alkane → alkene → alcohol → beta-ketothioester

what are acetoacetate and beta-hydroxybutarate

H2O soluble circulating fuel derived from fat (AKA KETONE BODIES)

beginning with excess Acetyl-CoA in the mitochondrion, describe the pathway it must take before it participates in cytosolic FA synth

XS Acetyl-CoA + OAA → citrate (mito) → citrate (cyto) + citrate lyase → Acetyl-Coa + OAA

1. load Acetyl-CoA to FA

2. use ACC to make malonyl-CoA

ACC equation

Acetyl-Coa + HCO3- + ATP → malonyl-CoA (better Nu)

where does acetyl-coa load

KS-Cys-SH part of FA synthase

where does malonyl-coa load

ACP-SH (pantetheine) part of FA synthase

FA synth FG steps

C-C bond formation, ketone → alcohol → alkene → alkane

at what number of carbons do you release your FA

C16

name of C16 fatty acid

palmitic acid

how to make a TAG after C16

C16 saturated FA + ELONGASES → C18/20 + DESATURASES → unsaturated FA

HOW TO MAKE GLYCEROL BACKBONE FOR FA

DHAP is reduced → glycerol-3-phosphate (backbone) → FA load → phospholipids & TAG

how are the production of ketone bodies and cholesterol synthesis related?

HMG-CoA can be used to produce acetoacetate OR if treated with HMG-CoA reductase, it forms cholesterol

need state lipid regulation

PKA active (inhibits ACC) → HORMONE SENSITIVE LIPASE → mobilizes FA to circulate with albumin → once inside cells it is activated (attached to CoASH) and puts on carnitine hat → inside mitochondria it undergoes beta-oxidation

fed state lipid regulation

XS acetyl-CoA in mito → INSULIN SIGNALS dephosphostate → ACC activated → Acetyl-CoA + OAA (mito) → citrate + citrate lyase → Acetyl-CoA + OAA (cyto) → FA synth OR malonyl-CoA formation (via ACC)

beginning with IPP and DMAP, discuss the assembly of cholesterol

IPP + DMAP → C10 + IPP → C15 + C15 → C30 (squalene) → squalene eoxidase + NADPH → lanosterol → 19 steps → cholesterol

what does bHLH domain do

increases transcription of genes for HMG-CoA reductase (RDS of cholesterol synth)

what is the regulatory domain on bHLH

SREBP (sterol regulatory element binding protein)

what is SCAP

SREBP cleavage activating protein

what does S1P protease do in cholesterol regulation

it snips the bond between bHLH and its regulatory domain to make bHLH active

when is S1P protease recruited?

when [cholesterol] is low

what is the normal cholesterol regulation

balance between Uptake (via RME and LDL) and Export (via ACBA1 transporter and HDL)

WHAT does the ABCA1 transporter do

displays XS cholesterol on the surface for HDL pickup

familial hypercholesterolemia

lack of LDL receptors → highly increased circulation of blood cholesterol (300-500 mg/dL)

tangier disease

no export of cholesterol because it is missing ABCA1 transporter, this results in inflammation