Fatty Acid Metabolism Flashcards by Taylor Nunes

Sources of fatty acids

Diet and synthesis in the liver in the fed state

How well did you know this?

Not at all

Perfectly

Major biological roles

post-translational modification, energy, membrane composition, hormones, and intracellular messenger

How well did you know this?

Not at all

Perfectly

Fatty acid and triacylglycerol synthesis occur in:

Cytoplasm (oxidation in the mitochondria)

How well did you know this?

Not at all

Perfectly

The true starting material for fatty acid synthesis

Citrate (TCA cycle intermediate)

How well did you know this?

Not at all

Perfectly

Acetyl CoA is converted to _____ by _____

Malonyl CoA
Acetyl CoA Carboxylase (ACC) - Rate limiting enzyme, irreversible step

Requires NADPH
Regulates fatty acid synthesis

How well did you know this?

Not at all

Perfectly

Malonyl CoA enters

Fatty acid synthase (FAS) which is used to synthesize palmitate form ACP and Vitamin B 5

How well did you know this?

Not at all

Perfectly

Acetly CoA can not be trasnported through the mitochondrial membrane so:

It is converted to citrate

How well did you know this?

Not at all

Perfectly

Citrate shuttle

Acetyl CoA is condensed with oxaloacetate to form citrate in the mito matrix

Citrate travels to the cytosol via citrate shuttle where it is converted back to Acetyl CoA and Oxaloacetate using the enzyme citrate lyase

How well did you know this?

Not at all

Perfectly

Acetyl CoA conversion to MalonylCoA requires:

Acetly CoA carboxylase and

ABC:
ATP
Biotin
CO2

How well did you know this?

Not at all

Perfectly

NADPH comes from:

PPP and malate to pyruvate conversion which requires malic enzyme

How well did you know this?

Not at all

Perfectly

__ NADPH equivalents are required for ____ carbon acetate units added

2, 2

How well did you know this?

Not at all

Perfectly

Fatty Acid Synthase (FAS)

Synthesizes palmitate from Malonyl CoA

It contains Acyl Carrier Protein (ACP)

Has cysteine residues at active site

Requires B5

How well did you know this?

Not at all

Perfectly

Net reaction for FAS cycle

8 acetyl CoA + 7 ATP + 14 NADPH + 14 H+ –> Plamitate + 8 CoASH + 7 ADP + 7 Pi + 14 NADP+ + 6H20

How well did you know this?

Not at all

Perfectly

Elongation

performed by elongases

adds 2 C sequentially

Requires NADPH

How well did you know this?

Not at all

Perfectly

Initial elongation converts _____ to ______

Palmitate to Stearate

How well did you know this?

Not at all

Perfectly

Desaturation

Desaturases

Adds double bonds

Requires O2, NADH and cytochrome b5

How well did you know this?

Not at all

Perfectly

Linoleic and linolenic acids are used to synthesize

Arachidonic acid which is the precursor for eicosanoids

How well did you know this?

Not at all

Perfectly

Allosteric regulation of ACC

Citrate - feed forward activation

Palmitoyl CoA - feed back inhibition

How well did you know this?

Not at all

Perfectly

High AMP levels

Inhibits ACC through phosphorylation using AMPK

How well did you know this?

Not at all

Perfectly

____ and ____ inhibit Acetyl CoA carboxylase (ACC) by ____

Glucagon and epinephrine

Phosphorylation

How well did you know this?

Not at all

Perfectly

_____ deactivates Hormone sensitive lipase by _____

Insulin

activating phosphatase which dephosphorylates Hormone-sensitive lipase

How well did you know this?

Not at all

Perfectly

_____ inhibits carnitine acyltransferase 1 (CAT1)

Malonyl CoA

How well did you know this?

Not at all

Perfectly

Inhibition of Acetyl CoA carboxylase promotes ______ of fatty acids

Oxidation

Deficiency of essential fatty acids causes

Dermatitis and poor wound healing

Excess of fatty acids causes

Resynthesis of triacylglycerol and storage in fat droplets - produces fatty liver

_____ are the major energy reserve in the body They are never use by these two systems in the body:

Triglycerides Brain and RBCs

Rate limiting step in the oxidation of fatty acids

carnitine palmitoyl-transferase-1 - for palmitate only (carnitine acyltransferase 1) Transports fatty acids to the mitochrondrial matrix for oxidation

beta-oxidation of fattyl acyl CoA produces

Acetly CoA, NADH, FADH2

Fatty acids which requires carnitine to be shuttled into _______

Long chain fatty acid Mitochondria

Fatty oxidation in the _____ is ________

liver, unregulated

The only point of regulation of fatty oxidation with _____ is

hormones | hormone sensitive lipase in the fat cells

The brain adapts to the use of ketone bodies during fasting state by:

Converting them to the to glucose for energy

non ketotic hypoglycemia is caused by

Deficiencies in fatty acid oxidation lead to

Fat metabolism in fasted state General overview

low insulin to glucagon ratio causes fatty acid release from adipose triglycerides are degraded to fatty acids and glycerol (by Hormone-sensitive lipase) and sent to liver and energy requiring tissues Free fatty acids carried to blood stream and bound to albumin FAs dissociate from albumin and are transported into cell

Hormone sensitive lipase allosteric effectors (in triglycerol degradation)

Insulin (-) | Epinephrine, GH (+)

Carnitine shuttle

Transports ≥ 14 C FAs to mito membrane Carnitine acyltransferase I - outer surface of inner membrane of mito (rate limiting) Translocase - transports conjugates across inner membrane Carnitine acyltransferase II - inner surface of inner membrane - carnitine --> fatty acyl CoA

Beta-oxidation is the ______ of synthesis

reversal

beta-oxidation summary:

Palmitoly CoA + 7 CoA + 7 FAD + 7 NAD + 7 H2O --> 8 acetyl CoA + 7 FADH2 + 7 NADH + 7 H+ Palmityl CoA under goes 7 rounds of b-oxidation

ATP produced from beta-oxidation of palmitoyl CoA

106

Major difference betwenn odd and even fatty acid metabolism

succinyl CoA is used as a substrate for gluconeogenesis and Acetyl CoA is not

Very Long Chain Fatty Acids (VLCA)

can not enter the mitochondrial matrix so are oxidized to short and medium chain FAs in the peroxisome

alpha-oxidation of BCFAs

Required for metabolism of plants

Unsaturated fatty acids

Enoyl CoA Isomerase moves cis double bond to trans double bond

MCAD Deficiency

Defect in Medium-chain acyl CoA dehydrogenase MItochondria Dixarboxylic acid build up Vommiting, lethargy, hypoglycemia

Methylmalonyl acidemia

Defect in methylmalonyl CoA mutase and adenosylcobalamin deficiencies Progressive encephalopathy, seizures, ketosis, acidosis

Odd number fatty acid metabolism

Propionyl CoA (propionyl CoA carboxylase - Biotin) > methylmalonyl CoA (methylmalonyl CoA mutase - B12) > Succinyl CoA Met, Ile and Val also feed into thos reaction to form propionyl CoA

Adult refsum disease

Deficiency of phytanoyl-CoA hydroxylase Build up of phytanic acid in peroxisomes Symptoms- neuropathy, cerebellar ataxia, shoretning of 4th toe and hearing loss

Odd chain fatty acid oxidation

Odd chain fatty acid OR Met, Ile, Val --> Propionyl CoA (by propionly CoA carboxylase) --> Methylmalonyl CoA (by methymalonyl CoA mutase) --> Succinyl CoA --> TCA cycle

Even chain fatty acid oxidation

Palmitate --> Acyl CoA (by fatty acyl CoA synthetase) --> Acyl carnitine (by carnitine palmitolyl trasnferase I) --> Acyl CoA (by Acyl CoA dehydrogenase/medium chain Acyl CoA dehydrogenase) --> trans enoyl CoA --> Acetyl CoA --> CO2 or Ketone Bodies

Fatty Acyl CoA synthetase uses:

ATP and Coenzyme A

Carnitine palmitoyl transferase 1 or (CAT 1) uses:

Carnitine

Palmitate is a ___ C FA

Rate limiting step of fatty synthesis and its allosteric effectors

Acetly CoA Carboxylase +Citrate - feed forward activation Activator: Insulin -Palmitoyl CoA - feed back inhibition Inhibitor: Glucagon Epinephrine AMP

Rate limiting step of fatty oxidation and its allosteric effectors

Carnitine Acyl Transferase I Malonyl CoA

Hormone sensitive lipase is important in

triglycerol degradation

_____ activates Hormone sensitive lipase by _____

Norepinephrine and epinephrine phosphorylation

Insulin does what to ACC?

Activates it through dephosphorylation