Overview Structure long chain of carbons with carboxyl group on one end can have a variable amount of double bonds double bonds make a fat unsaturated naturally in a cis configuration trans fats are unnatural and created via hydrogenation of vegetable oils ↑ risk of atherosclerosis double bonds ↓ melting temperature plant fat (e.g. olive oil) is unsaturated and liquid at room temperature animal fat (eg. butter) is saturated and solid at room temperature nomenclature e.g. palmitic acid C16:0 16 carbons with no double bonds numbered with carboxyl carbon as 1 e.g. linoleic acid C18:2 (9,12) 18 carbons with 2 double bonds (one at the 9th and one at the 12th carbon) omega system count opposite to the numbered system (i.e. carboxyl carbon is counted last) used to number unsaturated fats e.g. linoleic acid omega 6 family double bond at position "12" is 6 in from the opposite side (18 carbons in total) Essential fatty acids (FA) cannot be synthesized examples linoleicacid omega 6 can be used as a precursor for arachidonic acid becomes an essential fatty acid if linoleic acid is absent linolenic acid omega 3 ↓ risk of CV disease remember: omega 3 saves you from triple bypass found in cold water fish, nuts Transport see Lipoprotein topic Synthesis FA synthesis pyruvate (carbohydrate) → acetyl-CoA activated by insulin functions to store excess carbs as fat occurs in the mitochondria via pyruvate dehydrogenase acetyl-CoA + oxaloacetate → citrate shuttled out of mitochondria into cytoplasm citrate shuttle split back to acetyl-CoA and oxaloacetate acetyl-CoA + CO2→ malonyl-CoA catalyzed by acetyl-CoA carboxylase biotin required activated by insulin malonyl-CoA → CO2 + 2 carbons on fatty chain catalyzed by FA synthase requires NADPH humans make palmitic acid (16:0) as stored fat only de novo fat possible for 1 palmitic acid requires 8 acetyl-CoA 7 ATP 14 NADPH Catabolism Break down via β-oxidation occurs in hepatocytes, myocytes, adipocytes neurons cannot use fat as energy FAs do not cross BBB pathway location differs based on length of FAs short/medium (2-12 carbons) diffuse in mitochondria long (14-20 carbons) utilizes carnitine shuttle carnitine added to FA in the intermembrane space of the mitochondria catalyzed by carnitine acyltransferase (CAT) -1 inhibited by malonyl-CoA so as to prevent newly synthesized FAs from being degraded carnitine: FA transported into the matrix catalyzed by the carnitine transporter primary carnitine deficiency caused by carnitine transporter defect presentation lethargy irritability nonketotic / hypoketotic hypoglycemia triggered by catabolic states (e.g., fasting or illness) carnitine exchanged for CoA catalyzed by carnitine acyltransferase (CAT)-2 clinical importance myopathic CAT deficiency presentation myoglobinuria muscle aches/weakness ↑ TG content in muscles unable to use as energy provoked by prolonged use of muscle very long (>20 carbons) oxidized in peroxisome β-oxidation pathway occurs in the mitochondrial matrix reverses FA synthesis removing an acetyl-CoA and producing NADH and FADH2 catalyzed by fatty acyl-CoA dehydrogenase two types long-chain acyl-CoA dehydrogenase (LCAD) medium-chain acyl-CoA dehydrogenase (MCAD) blocked by ackee fruit toxin creates most of the energy used by the liver acetyl-CoA created in liver does not enter the citric acid cycle forms ketones see Ketone bodies topic clinical importance MCAD deficiency presentation non-ketotic hypoglycemia C8-C10 acyl carnitines in the blood liver unable to break FAs down further than C8-C10 no ketone bodies liver unable to produce ketones from β-oxidation fasting hypoglycemia liver unable to produce enough energy from β-oxidation to supply gluconeogenesis symptoms often precipitated by infection or stress treatment low fat diet with frequent meals of high carbs