fat metabolism

what are the two ways fat gets to cells?

• directly from food we contain via chylomicrons

• from the liver in the form of VLDLs

what organ is the central organ for fatty acid metabolism?

liver

what VLDLs do?

deliver packaged fat to peripheral tissues

where are VLDLs manufactured?

the liver

what do VLDLs attach to and interact with?

they attach to muscle and fat cells and interact with lipoprotein lipase and triglycerides are taken into the cells

how are LDLs (cholesterol) removed from the blood?

by LDL receptors on the plasma membrane (particularly liver cells- 70 to 80% of LDL is removed by the liver)

what does the liver use cholesterol to produce?

bile and steroid hormones

what happens if there is not enough functioning LDL receptors?

LDL cholesterol cannot be efficiently cleared from the blood

what happens when LDL accumulates in the bloodstream?

leads to hypercholesterolemia

do saturated fats and trans fats increase or decrease the number of LDL receptors?

decreases the number of receptors

• when dietary saturated fat intake is high, it leads to an increase in intracellular cholesterol levels in the liver

• the liver senses this excess cholesterol and responds by reducing the production of LDL receptors

• with fewer receptors available, less LDL is taken up from the bloodstream, leading to higher circulating LDL levels

do fiber and plant sterols increase or decrease the number of LDL receptors?

increase

does obesity increase or decrease the number of LDL receptors?

decreases

• obesity reduces the livers ability to regulate lipid metabolism

• insulin normally helps maintain LDL receptor expression, but when insulin resistance develops, LDL receptor production decreases

• with fewer LDL receptors, the liver clears less LDL from the bloodstream, causing LDL cholesterol to accumulate

does genetic mutations (familial hypercholesterolemia) increase or decrease LDL receptors?

decreases

where is HDL formed?

the bloodstream

what does HDL do?

it picks up excess cholesterol and delivers it to the liver

what is the only organ in mammals that can break down cholesterol and excrete it as bile?

the liver

what does picking up cholesterol require?

several receptors and enzymes

• the final step is when HDL binds with receptors and deposits cholesterol in the liver

the amount of HDL in the blood determines what?

cholesterol levels

what levels of lipids do blood tests measure?

• LDL

• HDL

• triglycerides

• ratio of LDL to HDL

what disease is saturated fat related to?

heart disease

• it is important to decrease saturated fat

• replacing saturated fatty acids with polyunsaturated fatty acids is more beneficial

• replacing saturated fatty acids with carbohydrate may increase CVD risk

what are the metabolic pathways for fat metabolism?

• lipogenesis

• lipolysis

• beta oxidation

• ketogenesis

what is lipogenesis?

synthesis of triglycerides (stored fats)

what is lipolysis?

breakdown of triglycerides to fatty acids

what is beta oxidation?

oxidation of fatty acids for energy

what is ketogenesis?

synthesis of ketone bodies for energy

after LPL hydrolyzes triglycerides, what does the cell do with the fatty acids?

• fatty acids can be metabolized immediately for energy

• fatty acids can be stored as energy by reforming into triglycerides (re-esterification)

• glycerol cant be metabolized by adipose cells and is transported to the liver - glycolytic pathway

• in most cells, fat is continually turning over- being broken down and re-esterified

how does the fat cell know whether to break down or build up fat?

• fat cells regulate fat storage and breakdown in response to a variety of hormonal and metabolic signals

• these processes are tightly controlled by the body’s energy balance, nutritional state, and physiological needs

what happens in the fed state after a meal?

• insulin dominates, promoting fat storage (lipogenesis)

• insulin stimulate lipoprotein lipase to breakdown and bring more fat into the cell from chylomicrons

• simultaneously insulin inhibits hormone sensitive lipase from breaking down stored triglycerides

what is the result after a fed state?

re-esterification of fat to be stored

what promotes fat breakdown in the fasted state?

glucagon, catecholamines, and cortisol

what is the major hormone that regulates lipolysis?

epinephrine

what other factors stimulate lipolysis?

peptides and other hormones

what is the result of lipolysis?

triglycerides are broken down into glycerol and 3 fatty acids

what are stored triglycerides in adipose tissue broken down into?

• free fatty acids are released into the bloodstream

• oxidation of fatty acids occur in the mitochondria - aerobic process

• glycerol is transported to the liver for gluconeogenesis

• this process is regulated by hormones like glucagon, epinephrine, and cortisol

why are fatty acids completely oxidized?

to produce energy known as beta oxidation

what does oxidation of fatty acids generate?

acetyl coa, NADH, FADH2 which are used for energy production

what happens when fatty acids enter the cell?

they are activated by coenzyme a to acyl coa

where is acyl coa transported to?

the mitochondria where beta oxidation occurs

• short chain fatty acids can move directly into the mitochondria

• long chain fatty acids must cross into the mitochondria using a transport system (requires carnitine)

what do fatty acids attach to to form acyl coa?

coenzyme a

where does acyl coa enter to lose 2 carbons?

the mitochondria

when beta oxidation is repeated what happens to the acetyl group?

one is released from the fatty acid each time

when acetyl coa enters the citric acid cycle what does it generate?

NADH and FADH2

what are NADH and FADH2 used for?

used in the electron transport chain to produce ATP

what are the end products of beta oxidation?

shorter chain fatty acids and 1 acetyl coa module

• acetyl coa enters the tca cycle

• remaining fatty acid goes through the beta oxidation cycle again

how much energy does 1 FADH2 produce?

1.5 ATP

how much energy does 1 NADH produce?

2.5 ATP

how much energy does acetyl coa produce?

11.5 ATP

how much total energy is produced from beta oxidation?

15.5 ATP

what is energy metabolism?

carbohydrate, fat, and protein work together to provide the body with energy

• most tissues in the body can metabolize fat for energy

what are ketones?

an alternative source of energy when glucose, fatty acids, and amino acids cannot provide the body with enough fuel

what is the normal level of ketones in the blood?

low

when does blood levels of ketones increase?

• when more fatty acids are in the blood that the tissues can oxidize

• there is not enough glucose available to supply glucose dependent tissues and other energy needed

what does the liver do to excess fatty acids?

converts them to ketones through a process called ketogenesis

what does the body do when glucose is scarce?

the boyd starts breaking down fat into acetyl coa molecules, which then combine in the liver to form ketone bodies (acetoacetate, beta hydroxybutyrate, and acetone)

what happens when insulin is absent?

uncontrollable ketone production leads to ketoacidosis, a dangerous condition in diabetes

what are the 2 drivers for ketogenesis?

• decrease in oxaloacetate

• increase in beta oxidation

what happens to acetyl coa in the liver?

it is shunted in ketogenesis

what do ketone bodies result in?

energy production when they enter the tca cycle via acetyl coa

which enzyme is responsible for getting fatty acids into cells?

lipoprotein lipase

hyperglycemia can result in lipogenesis

true

where does beta oxidation occur?

in the mitochondria

when the number of LDL receptors is low, blood cholesterol level is also low

false

when are ketone bodies produced in large numbers?

prolonged fasting