Fatty Acid Synthesis Flashcards
where is fatty acid synthesis
- primarily in the liver and adipose tissue
- also occurs in mammary glands during lactation
- wihtin cells, FAs occurs in the cytoplasm
- *oxidation is mitochondrial
what do you need for FA synth and what is the problem
- Acteyl CoA
- HCO3
- NADPH
- ATP
- the problem is that acetyl CoA is made in the mitochondria
acetyl CoA is made forom what that comes from what
-made from citrate that comes from the mitochondria
acetyl CoA carboxylase
- first makes malonyl CoA
- uses bicarbonate and acetyl CoA as reactants and biotin as a cofactor
- ATP dependent
first committed step in FA synthesis
- synthesis of malynoyl CoA
- therefore Acetyl CoA carboxylase is tightly regulates
regulation of acetyl CoA carboxylase
- via hormonally regulated phosphorylation
- when in the phosphorylated form, it is inactive
- inactivators: malonyl CoA, palmitoyl coA, and protein kinase
- activators: citrate, protein phosphotase
fatty acid synthase
- uses malonyl Coa, acetyl CoA and reduced NADPH to form FA chains
- levels increase by about 70x with a CHO rich meal after a fast
- dimer of two identical polypeptides, each with 7 enzymatically activies and 2 active sulfhydryls for forming thioester bonds
prosthetic groups of FAS
- Cys-SH
- phosphopantetheine
- pant covalently linked via a phosphate ester to a serine OH of the acyl carrier protein domain of FA synthase
- the long flexible arm of the phosphopantetheine helps its thiol to move from one active site to another within the complex
finishing FA synthesis
- synthesis proceeds by two carbon units until 16 carbons
- thioesterase cleaves off C16 palmitate, leaving FAS ready for another cycle
sources of NADPH for FA synthesis
-most NADPH comes from pentose phosphate shunt
elongases
-add 2 C units from acetyl CoA or malonyl CoA to carboxyl end, followed by reduction and dehydration
desaturases
- ass cis double bonds, generally spaced by 3 C’s
- in mammals never closer than omega 7
oxygenases
-oxidized polyunsaturated FA’s to create intracellular messengers
hydroxylases
-add OH to alpha carbon C2 of some FAs used in nervouse tissue
elongation adds to
the carboxyl end, therefore the omega number does not change
FA desaturase mechanism
- located on membrane surface of SER
- uses molecular oxygen, NADH, and cytochrome b5 to yield a double bond, water and NAD+
- double bond generally 3 carbons apart
- human enzymes can only desaturate at omega 7 or greater (further from terminal methyl)
essential fatty acids
- omega 3 and omega 6 are important in membranes as precursors for intracellular signaling molecules (prostaglandins and leukotrienes)
- must get from diet: linolenic (omega 3) and linoleic (omega 6)
sources of essential FA’s
linoleic: 20-80% of almost all plant oils
- linolenic: linsee, canola, coybean, walnut (herring oil)
what does the absence of glycerol kinase in adipose tissue mean
-that glycolytic products are needed for fat storage
what does acyl CoA synthetase do?
activates intracellular long chain fatty acids
ketone bodies
- during fasting glycogen reserves are depleted, glucose levels in the blood are low, and most tissues get energy from FA oxidation
- The blood brain barrier prevents albumin carrying FA’s from entering the brain
- To deal with this, the liver converts FA’s to ketone bodies, which can travel freely through the blood to the brain and other tissues
- there is no human enzyme to convert Acetyl CoA to pyruvate, therefore FA’s can not be used for gluconeogenesis
under what circumstances to ketone bodies form
- when carbohydrate is scarce, TCA cycle slows due to use of OAA in gluconeogenesis
- Acetyl CoA from beta oxidation accumulates in mitochondria and thiolase works in reverse
ketoacidosis
- ketone bodies build up in the blood when they are made faster than they can be used
- occurs in extreme starvation due to depletion of OAA arresting TCA
- also occurs in diabetes due to uncontrolled signal to release unneeded FA’s
- loss of ketone bodies in the urine causes loss of associated NA and K counter ions
- reduces the buffering capacity of the blood, causing a drop in blood pH
- uncontrolled ketoacidosis can result in death, and is a major problem in insulin dependent diabetics (type1)
why might low carb and high fat/protein diets work?
- glucagon stimulates FA release from adipose tissue
- ketone bodies increse and cause a mild ketoacidosis which may curb appetite
- protein intake may provide enough AA’s for gluconeogenesis
- without DHAP from glycolysis, TAG sythesis in adipose is low
why might the atkins diet not help?
- consequences of long term ketone-body/gluconeogenic metabolism is unknown
- not any more effective long term than any other restrictive diet
NIH recommended diet
- balanced, low cal
- exercise
