metabolic pathways and ATP production Flashcards
fatty acid metabolism: summarise the pathways for the synthesis and metabolism of fatty acids with respect to the substrates and products, coenzymes used, carrier molecules and their cellular locations; explain how inborn errors of fatty acid metabolism may cause disease
structure of a fatty acid
hydrophilic COO- head and hydrophobic hydrocarbon tail
saturated vs unsaturated fatty acid
saturated have no C=C and are solid; unsaturated have C=C present and are liquid
enzyme for desaturation
fatty acyl CoA desaturase
where is fat obtained
diet, liver (de novo), adipocytes
what does bile do
emulsify fats and increase their digestion and absorption
what is steatorrhea and how is it used to treat obesity
fatty stool; inhibit lipases
where does B-oxidation occur
mitochondria
sources of fatty acids
triacylglycerols, adipose
fatty acid to acyl CoA reaction
fatty acid + ATP + HSCoA → acyl CoA + AMP + PPi
what enzyme catalyses the conversion of fatty acids to acyl CoA, and where in the mitochondria does it act
acyl CoA synthase in outer membrane
how is acyl CoA transported into the matrix
via coupling to carnitine and entering via a translocase membrane
reaction of acyl CoA with carnitine, and enzyme
acyl CoA + carnitine ⇌ acyl carnitine, by carnitine acyltransferases
diagram of translocase
diagram from metabolism 6
acyl CoA → acetyl CoA: first step
acyl CoA oxidised by dehydrogenase enzyme (FAD → FADH2)
acyl CoA → acetyl CoA: second step
hydrated by hydrolase enzyme
acyl CoA → acetyl CoA: third step
oxidised by dehydrogenase enzyme (NAD+ → NADH + H+)
acyl CoA → acetyl CoA: fourth step
cleavage by reacting with HSCoA, catalysed by thiolase enzyme to form acetyl CoA and an acyl CoA
how many fewer carbons does the new acyl CoA have
2
acetyl CoA formation diagram
diagram from metabolism 6
palmitoyl as example of fatty acid: reaction
palmitoyl CoA + 7 FAD + 7 NAD+ + 7 H2O + 7 CoA → 8 acetyl CoA + 7 FADH2 + 7 NADH
how many B-oxidations required for palmitoyl
7 (16C → 8 acetyl CoA as last produces 2x acetyl CoA, as 4C intermediate)
what is the maximum number of ATP molecules produced by palmitoyl B-oxidation
129 ATP as 131 but 2 bonds broken: ATP → AMP+PPi
why can’t glucose be generated via gluconeogenesis in this pathway
pyruvate is not produced when fats are respired, so there is no conversion to oxaloacetate, so [oxaloacetate] decreases; therefore acetyl CoA from B-oxidation only enters TCA if balanced with carbohydrate metabolism
what happens to acetyl CoA when B-oxidation is greater than glycolysis (e.g. when fasting)
converted to ketone bodies in the liver
fat metabolism diagram
diagram from metabolism 9
acetyl CoA → fatty acid (lipogenesis): what enymes are required and where does it occur
acetyl CoA carboxylase and fatty acid synthase (FAS); occurs in cytoplasm
list the components associated with FAS
synthesising, transferring, dehydrating, reducing and hydrolysing; also contains acyl carrier protein (ACP), which is a swinging arm to move molecules (similar to PDH)
acetyl CoA → fatty acid (lipogenesis): first stage
formation of malonyl CoA by acetyl CoA carboxylase (+ HCO3-) and biotin coenzyme; ATP → ADP + Pi
acetyl CoA → fatty acid (lipogenesis): second stage
transfer of malonyl to ACP ro form malonyl-ACP (ACP → HSCoA)
acetyl CoA → fatty acid (lipogenesis): third stage
transfer of acetyl from acetyl CoA to ACP to form acetyl-ACP (ACP → HSCoA)
acetyl CoA → fatty acid (lipogenesis): fourth stage
condensation of malonyl-ACP and acetyl-ACP to form 4C fatty acid acetoacetyl-ACP
acetyl CoA → fatty acid (lipogenesis): fifth stage
reduction of acetoacetyl-CoA to 3-hydroxybutyryl-ACP (NADPH → NADP+)
acetyl CoA → fatty acid (lipogenesis): sixth stage
dehydration of 3-hydroxybutyryl-ACP to crotonyl-ACP
acetyl CoA → fatty acid (lipogenesis): seventh stage
reduction of crotonyl-ACP to butyryl-ACP (NADPH → NADP+)
how many times must stages 4 to 7 be repeated to form 16C palmitoyl-ACP
6
final stage reaction of acetyl CoA → fatty acid (lipogenesis) for palmitate
hydrolysis of palmitoyl-ACP to palmitate and ACP
summary reaction of acetyl CoA → palmitate (lipogenesis)
acetyl CoA (C2) + 7 malonyl CoA (C3) + 14 NADPH + 14 H+ → palmitate (C16) + 7CO2 + 6H2O + 8CoA-SH + 14 NADP+
how many more carbons does the fatty acid have
2
B-oxidation vs lipogenesis reaction sequences
B-oxidation: oxidation, hydration, oxidation, cleavage; lipogenesis: condensation, reduction, dehydration, reduction
diagram showing B-oxidation and lipogenesis differences
diagram from metabolism 6
B-oxidation and lipogenesis: difference in carriers
B-oxidation: CoA; lipogenesis: ACP
B-oxidation and lipogenesis: difference in reducing power
B-oxidation: NADPH; lipogenesis: FAD/NAD+
why is a family of acyl CoA dehydrogenases required
catalyse different lengths of fatty acids (fatty acids pocessed produce acyl CoA with 2 fewer carbons)
inborn disorders of fatty acid oxidation: MCAD deficiency
C6-C12; can’t break down FA beyond C6 so can’t generate acetyl CoA; can be fatal (especially if fasting); treated with a high carb diet and IV glucose
inborn disorders of fatty acid oxidation: primary carnitine deficiency
mutation in gene for carnitine transporter which lowers carnitine uptake; treated with carnitine supplements