Fatty Acids

BIOC13

AMPK

Key enzyme that shuts down many energy-consuming processes and increases energy production

mTORC1

Occurs when nutrients abundant, signalling promotes biosynthesis and proliferation

Lipid digestion step 1

emulsion to create lipid droplets

Lipid digestion step 2

Bile salts make lipid droplets more accessible to lipases

Lipid digestion step 3

Lipases cleave TAGs to glycerol and free fatty acids

Lipid digestion step 4

Fatty acids are carried as micelles for absorption

Insulin effect on lipolysis

Decreases, glucose already being broken down

Glucagon effect on lipolysis

Increases, gluconeogenesis needs energy

Fat storage

Lipid droplets in adipose tissue

Lipid Degradation Step 1

Lipolysis converts TAG into glycerol and free fatty acids

Lipid Degradation Step 2

FAs must be activated and transporter into mitochondria

Lipid Degradation Step 3

Breakdown of FA into acetyl CoA (β-oxidation)

Fate of glycerol

Glycolysis or gluconeogenesis

PKA effect on lipases

Activates for breakdown of TAGs

FA activation

Attachment to CoA by acyl CoA synthase

FA crossing inner membrane

FA is transferred to carnitine by carnitine acyltransferase I then transported by acyl carnitine translocase

FA Oxidation

oxidize fatty acid 2 carbons at a time to produce acetyl-CoA and harvest high energy electrons

FA Oxidation step 1

Oxidation, produces FADH₂

FA Oxidation step 2

Hydration

FA Oxidation step 3

Oxidation, generates NADH

FA Oxidation step 4

Cleavage to form acetyl CoA and FA chain 2 carbons shorter

FA Oxidation energy investment

2 ATP per FA

ATP produced per NADH donating to ETC

2.5

ATP produced per FADH₂ donating to ETC

1.5

Enzyme for odd-numbered double bonds

Enoyl CoA isomerase

Energetic cost of shifting odd-numbered double bond

FADH₂ from first oxidation

enzyme for even-numbered double bonds

2,4-dienoyl CoA reductase

Energetic cost of shifting even-numbered double bonds

Consumes 1 NADPH

Oxidation of odd-numbered FA chains

Last thiolysis generates propionyl CoA, which gets turned into succinyl CoA

Ketone bodies

acetoacetate, acetone, D-3-hydroxybutyrate

Ketone bodies produced when

Excess of acetyl CoA without sufficient oxaloacetate for TCA

Why would there not be enough oxaloacetate

not enough glucose metabolism (low blood sugar, diabetes), too much FA release

Ketone body use

Alternative fuel for low carb availability

Ketogenic acidosis

Ketone bodies are strong acids that can drop blood pH, kidneys can’t maintain pH leading to impaired tissue function, coma and death

FA Synthesis Step 1

Transport of acetyl-CoA as citrate out of mitochondria into cytoplasm

FA Synthesis Step 2

Malonyl CoA synthesized from acetyl CoA by ACC

FA Synthesis Step 3

Acetyl CoA and malonyl CoA attached to ACP

FA Synthesis Step 4

Elongation by 2 carbons at a time

Fatty Acid Synthase Complex

In animals, required enzymes (and ACP) are synthesized as a large polypeptide functioning as a dimer

FA Elongation step 1

Condensation

FA Elongation step 2

Reduction

FA Elongation step 3

Dehydration

FA Elongation step 4

Reduction

Precursor for subsequent rounds of elongation

acyl-ACP

Max # of carbons synthesized by elongation

C16

Enzyme that cleaves elongation

Thioesterase

Electron carrier consumed in FA synthesis

NADPH

Enzyme for introducing double bonds

Desaturase

Enzyme for extending beyond C16

Elongase