Ch. 21 - Lipid Metabolism

triacylglycerol (triglyceride)

main storage form of chemical energy for most organisms

phosphoacylglycerol

key component of biological membranes

lipases

enzymes that use H2O to release the fatty acids from ester bonds, releasing a free glycerol

Describe the 5 steps of how liberation of fatty acids is hormone-dependent—how it’s activated

1. hormone binds to membrane receptor on adipose cell surface

   • conformational change & signal that it’s time to spend triacylglycerols

2. adenylate cyclase turns ATP → cAMP (messenger molecule)

3. cAMP then activates protein kinase

4. kinase activates triacylglycerol lipase by adding phosphate from ATP

5. triacylglycerol lipase + triacylglycerol → DAG lipase + diacylglycerol → MAG + monoacylglycerol (nów 3 free fatty acids)

activation in lipid metabolism

thioester bond formed btw carboxyl group (COOH) of fatty acid & thiol group of CoA-SH

• catalyzed by Acyl-CoA synthetase—needs ATP

• now becomes Acyl-CoA

location of esterification & its ability to cross membranes

cytosol; Acyl-CoA can cross outer mitochondrial membrane but not inner

location of fatty acid oxidation after esterification

mitochondrial matrix

what is the overall rxn for the activation of fatty acid?

• equivalent to using 2 ATP

Carnitine

molecule in fatty acid metabolism that shuttle acyl groups across inner mitochondrial membrane

carnitine acyltransferase—carnitine palmitoyltransferase (CPT-I)

found on cytosol side of inner mitochondrial membrane w/ specificity for acyl groups 14–18 carbons long

carnitine palmitoyltransferase (CPT-II)

found in mitochondrial matrix

How is Acyl-Coa transferred into the mitochondrial matrix if it can’t get past the inner membrane? (3 steps-ish)

1. Acyl-CoA passes outermembrane into intermembrane space and transfers its Acyl group to carnitine by CPT-I

   • carnitine exchanges w/ CoA-SH → Acyl-carnitine

   • free CoA-SH goes back to cytosol & is recycled

2. Acyl-carnitine into matrix by a transferase (CPT-II)

3. Acyl-carnitine recombined w/ CoA-SH → activated acyl-CoA

   • released carnitine goes back to intermembrane space to be recycled

*can now start oxidizing it

saturated fat

single bond between carbons

e.x: butter

β-Oxidation

series of 4 rxns that cleaves off 2-carbon units from COOH end of fatty acid

• named after C_β in fatty acyl-CoA

*we will only focus on even numbered molecules w/ C–C (single bond)

Location of β-Oxidation

mitochondrial matrix

β-Oxidation: Step 1

activated fatty acyl-CoA + FAD → FADH₂ + double-bond carbons in what was acyl-CoA

• catalyzed by Acyl-CoA dehydrogenase

β-Oxidation: Step 2

hydration rxn—add H onto C_⍺ & OH on C_β (L-β-Hydroxyacyl-CoA)

• catalyzed by Enoyl-CoA hydratase

*not redox rxn

β-Oxidation: Step 3

NAD + L-β-Hydroxyacyl-CoA → NADH + H⁺ + β-Ketoacyl-CoA

• catalyzed by L-Hydroxyacyl-CoA dehydrogenase

• OH from C_β → C=O

β-Oxidation: Step 4

β-Ketoacyl-CoA + CoA-SH → Acetyl-CoA + Fatty acyl-CoA

• cleavage

  • broken btw C_β & C_⍺

  • C_⍺ side → acetyl-CoA

  • C_β side → fatty acyl-CoA (shorter by 2 carbons)

    • enter successive cycles until its portion becomes acetyl-CoA

• catalyzed by thiolase

total products from β-oxidation (per cycle)

• 1 NADH = 2.5 ATP

• 1 FADH₂ = 1.5 ATP

• Acetyl-CoA which will enter Krebs → ETC → ox. phos.

all contributing to making more ATP

ratio of ATP:Carbon from glucose

5.3:1

ratio of ATP:Carbon from fats

6.6:1

why fats is better storage of energy

How do ketone bodies come about

when amount of acetyl-CoA is excessive compared to oxaloacetate available to react w/ it

*think of KETO diet or even starvation or diabetic patients’ inadequate intake of carbs

3 compounds that make up ketone bodies

1. acetone

2. β-hydroxybutyrate

3. acetoacetate

Formation of ketone bodies: Step 1 *DON’T HAVE TO MEMORIZE JUST UNDERSTAND :D

2 acetyl-CoA → acetoacetyl-CoA + 2 CoA

• catalyzed by thiolase

  • acetyl group gets “fused” to acetyl-Coa & CoA gets KICKED TF OUT

Formation of ketone bodies: Step 2

addition of H2O + acetyl-CoA onto acetoacetyl-CoA while removing a CoA

• catalyzed by *long ass MF name—don’t need to memorize (HMG-CoA synthase) → product is HMG-CoA

Formation of ketone bodies: Step 3

HMG-CoA → acetoacetate

• cleaves (removes) an acetyl-CoA

  • catalyzed by HMG-CoA lyase

Formation of ketone bodies: Step 4

acetoacetate → acetone + β-Hydroxybutyrate

• acetoacetate SPONT. loses CO2 → acetone

• acetoacetate + NADH + H⁺ → β-Hydroxybutyrate + NAD⁺

  • catalyzed by β-Hydroxybutyrate dehydrogenase