Lipids in Energy Metabolism - FA & TG Flashcards
Lipid in blood transport
PL & TG: lipoproteins
FA: Bound to plasma proteins
Lipoprotein definition
Spherical lipid droplet containing at least one apoprotein
How are FA stored?
Oil droplets of neutral TG to prevent potential destruction to cell membranes, have high energy density
TG lipoprotein transport issues
Lipases release FA from stored TG
FA transported across membranes
TG resynthesized into TG
TG cycle - Dietary TG (direct step)
Dietary TG –> GI lipase –> FA
TG cycle - liver redistribution to tissues (3 items)
- Endocytoses CMR & releases TG
- Synth TG from FA (from meal glucose)
- Assembly & export of VLDL
Liver & TG
Assembles it into VLDL to be secreted
Only small amount of TG for local use
Adipose & TG
Stores TG in oil droplets for body and releases FA into plasma during fasting for fuel
FA synth from glucose (pathway)
Glucose –> pyruvate –> citrate –> Acetyl CoA – Malonyl CoA –> palmitate –> sat & unsat FA
FA synth from Acetyl CoA (pathway)
Acetyl CoA –> Malonyl CoA –> palmitate –> sat &a unsat FA
ATP Citrate Lyase (ACLY) fx
Citrate –> Acetyl CoA
Acetyl CoA Carboxylase (ACC) fx
Acetyl CoA –> Malonyl CoA
FA synthase fx
Malonyl CoA –> palmitate
Note that NADPH –> NADP at this step
FA synth is upregulated by
insulin
substrate levels
ACC regulation - stimulated by:
Insulin (+)
Citrate (+)
Fructose metabolism
Enters glycolysis after PFK-1 -
Metabolites activate ACC to induce FA synth
TG synth
Glucose –> FA –> acyl CoA
Glycolytic intermed DHAP –> glycerol –> glycerol-3-P
Acyltransferases
Attach an acyl CoA to glycerol-3-P –> TG
VLDL lipoprotein assembly is driven by ______, then immediately _____
Driven by TG, then immediately secreted
HSL definition and action
Hormone sensitive lipase
adipocyte specific lipase releases FAs + glycerol from TG
Fate of FA released from TG
Cellular fuel for muscle and other cells.
Fate of Glycerol from TG
Taken up by liver as substrate for gluconeogenesis
HSL regulation - stimulated by:
Glucagon (+)
Cortisol (+)
EPI (+)
Growth Hormone (GH) (+)
FA B-Oxidation products (2+1 items)
Acyl CoA –> NADH & FADH2
Acyl CoA –> Acetyl CoA
Where is plasma FA converted in acyl CoA for B-Ox?
Cytosol
Carnitine palmitoyl transferase 1 (CPT-1)
Transport Acyl CoA along with the carnitine shuttle into mitochondria for B-Ox
B-Ox enzymes function
Generate acetyl CoA & lots of NADH and FADH2 for ETC
Hepatocytic cytosolic FA are all converted into ____
Acyl CoA
Cytosolic Acyl CoA is transformed into
–> TG
Mitochondrial Acyl CoA is transported in by ____ and undergoes _____ to yield ____
Transported in by CPT-1
–>B-Ox –> ATP
Malonyl CoA inhibits _____ and is formed from ____ by _____
Inhib CPT-1
formed from citrate by ACCC
CPT-1 activity is always _____ unless ______ (inhib, stim) by _____
Always high unless inhibited by malonyl CoA
Acute lipid dysreg leads to
Ketoacidosis
Chronic lipid dysreg leads to
Atherosclerosis
Steatosis
Early form of fatty liver dz (FLD)
Hepatocytes accumulate excess TG
Acute effects unique to hyperglycemia
Hyperosmolar hyperglycemic state (HSS)
Chronic effects unique to hyperglycemia
Microvascular:
Retinopathy
Nephropathy
Neuropathy
Low insulin effect:
High glucagon:insulin ratio –> inc hep VLDL synth w dec conversion to remnants –> Excess VLDL –> Atherosclerosis –> CVD
Excess cytosolic acyl CoA increases
- Inc adipose lipolysis –> Inc hep FA uptake
- Inc hep de novo FA synth
Excess hepatic TG causes
- Excess cytosolic acyl CoA
- Dec assembly/export of VLDL
ACC regulation - inhibited by:
Glucagon (-) Acyl CoA (-)
HSL regulation - Inhibited by:
Insulin (-)
B-Ox enzymes - location
In mitochondria
When is [Malonyl CoA] low?
[Low] during fasting bc glucagon inhib ACC
When is [Malonyl CoA] high?
[High] when fed bc insulin inc ACC
What factors also tie into atherosclerosis?
Hyperglycemia,
HTN
obesity
Excess cytosolic acyl CoA decreases
-Dec hep FA ox
What role do capillaries play in the TG dietary cycle and tissue redistribution?
Lipoprotein lipase (LPL) in capillaries releases FA from TG, leaving CMR
What role does adipose play in TG dietary cycle and tissue redistribution?
Adipose FA uptake and TG synth
Fructose metabolism location
Only in liver
How are Acyltransferases regulated?
subtrate levels
Prognosis of steatosis
Benign, but can progress to steatohepatitis, w hep inflam and hep apoptosis
What role do enterocytes play in the TG dietary cycle?
TG synth and CM assembly
Fructose is uptaken by ____ during metabolism
GLUT5
Fructose metab reg/inhib
no allosteric inhib
Evades (-) feedback reg
FA released from TG is bound to _____
albumin
Pathway of fate of glycerol from TG
Glycerol –> kinase –> glycerol-3-P –> Dehydrogenase –> DHAP
CPT-1 fx
transports Acyl CoA into mitochondria for B-Ox
Steatosis is common with ______
Obesity
TDM
EtOH abuse
What does high [Malonyl CoA] cause?
[High] causes Acyl CoA to stay in cytosol