Fatty Acid Synthesis

Question 1

where is fatty acid synthesis

Answer 1

• primarily in the liver and adipose tissue
• also occurs in mammary glands during lactation
• wihtin cells, FAs occurs in the cytoplasm
• *oxidation is mitochondrial

Question 2

what do you need for FA synth and what is the problem

Answer 2

• Acteyl CoA
• HCO3
• NADPH
• ATP
• the problem is that acetyl CoA is made in the mitochondria

Question 3

acetyl CoA is made forom what that comes from what

Answer 3

-made from citrate that comes from the mitochondria

Question 4

acetyl CoA carboxylase

Answer 4

• first makes malonyl CoA
• uses bicarbonate and acetyl CoA as reactants and biotin as a cofactor
• ATP dependent

Question 5

first committed step in FA synthesis

Answer 5

• synthesis of malynoyl CoA

- therefore Acetyl CoA carboxylase is tightly regulates

Question 6

regulation of acetyl CoA carboxylase

Answer 6

• via hormonally regulated phosphorylation
• when in the phosphorylated form, it is inactive
• inactivators: malonyl CoA, palmitoyl coA, and protein kinase
• activators: citrate, protein phosphotase

Question 7

fatty acid synthase

Answer 7

• 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

Question 8

prosthetic groups of FAS

Answer 8

• 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

Question 9

finishing FA synthesis

Answer 9

• synthesis proceeds by two carbon units until 16 carbons

- thioesterase cleaves off C16 palmitate, leaving FAS ready for another cycle

Question 10

sources of NADPH for FA synthesis

Answer 10

-most NADPH comes from pentose phosphate shunt

Question 11

elongases

Answer 11

-add 2 C units from acetyl CoA or malonyl CoA to carboxyl end, followed by reduction and dehydration

Question 12

desaturases

Answer 12

• ass cis double bonds, generally spaced by 3 C’s

- in mammals never closer than omega 7

Question 13

oxygenases

Answer 13

-oxidized polyunsaturated FA’s to create intracellular messengers

Question 14

hydroxylases

Answer 14

-add OH to alpha carbon C2 of some FAs used in nervouse tissue

Question 15

elongation adds to

Answer 15

the carboxyl end, therefore the omega number does not change

Question 16

FA desaturase mechanism

Answer 16

• 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)

Question 17

essential fatty acids

Answer 17

• 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)

Question 18

sources of essential FA’s

Answer 18

linoleic: 20-80% of almost all plant oils

- linolenic: linsee, canola, coybean, walnut (herring oil)

Question 19

what does the absence of glycerol kinase in adipose tissue mean

Answer 19

-that glycolytic products are needed for fat storage

Question 20

what does acyl CoA synthetase do?

Answer 20

activates intracellular long chain fatty acids

Question 21

ketone bodies

Answer 21

• 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

Question 22

under what circumstances to ketone bodies form

Answer 22

• 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

Question 23

ketoacidosis

Answer 23

• 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)

Question 24

why might low carb and high fat/protein diets work?

Answer 24

• 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

Question 25

why might the atkins diet not help?

Answer 25

• consequences of long term ketone-body/gluconeogenic metabolism is unknown
• not any more effective long term than any other restrictive diet

Question 26

NIH recommended diet

Answer 26

• balanced, low cal

- exercise