Question

MCAT Biochemistry Tutorial: Fatty Acid Metabolism

Answer 1

\({\bf{Oxidation:}}\)
- triglycerols are broken down into: their FFA (free fatty acid) chains and the glycerol backbone
- glycerol gets degraded w/ glycolysis
- FFA's are bound to albumin and transported to mitochondria
> if C# > 14: series of reactions needed first before transport occurs
1. combine fatty acid with acetyl CoA (uses ATP)
2. exchange of CoA w/ carnitine -> transport across membrane -> exchanges CoA w/ carnitine from the other side

> if FFA is saturated and has even C#: acetyl-CoA groups are "clipped" and oxidized in citric acid cycle
1. add double bond
2. hydrates the double bond by forming beta hydroxyl-acyl CoA
3. oxidize beta hydroxyl bond and form a beta-ketoacyl-CoA
4. beta-ketoacyl CoA is attacked at acetyl-S-CoA
5. CoA-SH is replaced
6. cycle continues until only acetyl-CoA is left

Overall Equation:
palmitoyl-CoA + 7Co-A + 7FAD + 7NAD+ --> 8 acetyl-Co-A + 7FADH2 + 7NADH + 7H+

electron transfer -> 28 ATP + 10*(8 acetyl CoA) = 108 ATP produced

> if FFA has odd #C or is unsaturated:
- double bonds --> enzyme converts FFA to trans form
- odd carbon#: produces propionate-CoA --> conversion to succinyl

> very long/branched FFAs: may be oxidized in perioxisomes

Omega Oxidation: starts in ER --> carbon attack on the omega end --> fatty acids --> combined with acetyl CoA --> oxidation via beta pathway in mitochondria

Answer 2

\({\bf{Ketone~Bodies:}}\) acetone, acetoacetate, beta-hydroxybutyrate
- low carb intake --> metabolism becomes ketone based
- diabetic ketoacidosis: may result in too much acetyl CoA production and too high ketone elevation (results in excessive acidity)
- general mechanism: acetyl CoA --> aceto-acyl CoA --> acetoacetate --> either beta-hydroxybutyrate or acetone are formed

Answer 3

\({\bf{Anabolism:}}\) starts with addition of carboxyl group to acetyl-CoA to make malonyl-CoA

Overall Eqn: 7 malonyl-CoA + acetyl-CoA + 14H+ + 14NADPH --> palmitic acid + 7CO2 + 8CoA + 14NADP+ +7H2O

7 reactions, two C's transferred per cycle

unsaturated fatty acid production: mammals can only desaturate at Δ9 or carbonyl
- essential fatty acids: add double bonds
- linoleic acids: carbon framework for eicosanoid synthesis --> can be used for triacylglycerols + membrane synthesis

Regulation of anabolism:
- anabolism takes place in a different cytoplasm under a different set of enzymes
- hormones like epinephrine and glucagon release FFAs from doplets
- malonyl-CoA inhibits carnitine shuttle
- citrate, palmitoyl-CoA stimulate/suppress synthesis respectively

Answer 4

\({\bf{Cholesterol~Synthesis:}}\)
- combination of 3 acetyl-CoA into HMG CoA
- smooth ER: HMG CoA reductase + nadph --> mevalonate formation
- decarboxylase: converts mevalonate into isoprene (Δ3-isopentyl pyrophosphate)
- condensation --> geranyl PP1 formation -- addition of another Δ3-isopentyl pyrophosphate --> formation of farnesyl PP1
- formation of squalene (uses 18ATP + 13 nadph)
- conversion into 2,3-epoxide by squalene monooxygenase
- collapse of four ring structure into lanosterol

Further Use/Processing of Cholesterol:
- formation of bile acids
- esterification
- transport via apoproteins
- steroid hormone synthesis via oxidases
> forms water
> nadph hydrogen donor
> cytochrome p-450 intermediate

Answer 5

Anyway, that's the end of my tutorial, I hope it was a helpful resource. Source material is the 2nd Edition Barron's Prep book for the new MCAT