integrated metabolism

what are the metabolic pathways for carbohydrates?

• glycolysis

• tca/etc

• pentose phosphate

• glycogen pathways

what are the metabolic pathways of fat?

• lipolysis with beta oxidation

• tca/etc

• ketogenesis

• fatty acid and cholesterol synthesis

what are the metabolic pathways of protein?

• transamination

• deamination

• gluconeogenesis

• lipogenesis

• ketogenesis

• tca/etc

are all the pathways intertwined and linked together?

yes

what pathway do carbohydrates, fats, and proteins share?

tca and electron transport chain

what do catabolic pathways do?

break down nutrients to release energy

what do anabolic pathways do?

synthesizes compounds and uses energy

what are the three key entry points that these pathways have in common?

• pyruvate

• oxaloacetate

• acetyl coa

if a cell needs energy (catabolic), what occurs to pyruvate?

pyruvate will be converted to acetyl coa and will go to the mitochondria through the tca cycle and electron transport chain

if a cell does not need energy (anabolic), what occurs to pyruvate?

pyruvate is mostly converted to glucose and stored as glycogen or acetyl coa is used for fatty acid synthesis

what is cell homeostasis?

process involved in the maintenance of an internal steady state

enzymes are unidirectional which means what?

their reactions are irreversible

how are enzymes controlled?

respond to cellular signals

what is increased to increase catabolic reactions?

• atp

• acetyl coa

• citrate

what is increased to increase anabolic reactions?

• adp

• amp

• malonyl coa

after a meal, what happens to glucose, fatty acids, and amino acids?

they increase in the bloodstream

after glucose, fatty acids, and amino acids are in the bloodstream, what do cells do?

they take them up and begins to break them down through glycolysis, transamination and deamination, and beta oxidation

what builds up in the cells after these processes?

• atp

• acetyl coa

• citrate

what is important in fatty acid synthesis and beta oxidation after a meal?

acetyl coa and manoyl coa

if energy is not needed after a meal, what happens to acetyl coa?

it is converted to manoyl coa which is the first step of fatty acid synthesis

what do glucose and insulin blood levels in the muscle cells do?

increase the conversion of acetyl coa to manoyl coa which inhibits fatty acid breakdown

what regulates metabolism?

ampk

what does ampk do?

regulates both catabolic and anabolic pathways for all micronutrients

what activates ampk?

its activated through changes in amp to atp ratios in the cellwhat causes

what causes higher amp to atp ratios?

• fasting

• muscle contractions

• metabolic stresses

what does ampk do?

• stimulates cell membrane transporter to glucose uptake into cells

• stimulates glycolysis (particularly in heart muscles)

• inhibits cellular energy from being used for anabolic processes

• stimulate increased fatty acid uptake by cardiac muscles

• inhibits protein synthesis

• stimulates the hypothalamus to increase appetite

what provides the majority of the energy in atp production?

dietary carbohydrates and fat

where is the majority of the protein we eat go to?

protein synthesis

when are proteins used for energy?

when carbohydrate and fat intake are low

what are amino acids precursors for?

glucose or fatty acid synthesis

what can glucose and amino acids be converted to?

pyruvate

once converted to pyruvate, where does it goes?

• can be transported to the mitochondria and converted to acetyl coa

• acetly coa is then oxidized to produce atp

what needs to happen to acetyl coa for fatty acids to be synthesized?

acetyl coa has to be transported out of the mitochondria by combining with oxaloacetate to form citrate

what can glucose be converted to when glycogen storage is maximized?

• glycerol

• fatty acids through acetyl coa

what are the two forms of amino acids?

• glucogenic- produce glucose

• ketogenic

what is allosteric control?

short term

what is hormonal control?

long term

what organs and tissues is fuel sources balanced between?

• liver

• muscle

• adipose tissue

• brain

• blood

• kidneys

what organ plays a central role in metabolism?

liver

what does glucose get converted to?

glucose-6-phosphate

what are the uses of glucose-6-phosphate?

• 2/3rds of glucose-6-phosphate comes from dietary glucose

• 1/3rd is from gluconeogenesis driven by lactate

what is the primary site of glycogen storage?

liver

what synthesizes in the liver?

• cholesterol

• lipoproteins

• triglycerides

what type of muscles cells require constant supply of energy?

cardiac

what type of muscle cells have low requirements at rest?

skeletal

what type of muscles cells stroe glycogen?

skeletal

what is the primary fuel for skeletal and cardiac cells?

fatty acids when at rest or moderate activity

what else do muscle cells use for fuel?

ketones

what has a large capacity for triglycerides?

adipose cells

what do adipose cells do?

• store fat by re-esterification of fatty acids to triglycerides

• take in glucose and oxidize it for immediate needs and then store the rest as fat

what does lipogenesis require?

NADPH from the pentose phosphate pathway

what is the primary fuel store of the brain?

glucose

what percentage of energy does the brain use?

20-25%

can the brain use ketones?

some but only when necessary

what do red blood cells use as their energy source?

exclusively use glucose

• does not contain mitochondria

• all their energy comes from glycolysis

where does lactate from glycolysis go?

back to the liver and is recycled into more glucose

what percentage of energy do kidneys use?

10%

what do kidneys do?

they filter blood and retain water, nutrients, and glucose

what does the renal medulla use for fuel?

glucose

when do the kidneys do during starvation?

the kidneys ramp up during and may contribute half of blood glucose through

• gluconeogenesis

• conversion of lactate to glucose in the renal cortex

how are the systems multidirectional?

• direction is controlled at the cellular level over the short term

• regulated by hormones for long term control

how long does the fed state last?

up to 3 hours after eating a meal

• characterized by elevated insulin

how long is the postabsorptive state?

3 to 18 hours after a meal

• glucagon begins to rise

how long does the fasting state last?

18 hours to 2 days after a meal without any additional food

• further increases in glucagon levels

how long does the starvation state last?

food deprivation lasting more than 2 days

what do fed and fasted states last?

• activity level

• caloric content of the meal

• nutrient content of the meal

• person’s metabolic rate

• rate of absorption

what happens in a fed state?

• most tissues immediately use some glucose from the rice and vegetables for fuel

• the brain and blood cells use glucose for all their energy needs in the fed state (they don’t have the capacity to store glucose or fatty acids)

• when glucose from the meal exceeds immediate energy needs

• stored as glycogen in the liver and skeletal muscle

• once glycogen capacity is reached, excess glucose can be converted to fat in the liver

• conversion of glucose to fat only occurs in the fed state

after glucose is converted to fat, what happens to the fat in the fed state?

• at the same time fat is also delivered to other tissues

• adipose cells uptake glucose and fatty acids from the rice, vegetables, and chicken

• both glucose and fatty acids are used by adipocytes for immediate energy

• excess glucose or fatty acids is converted to triglycerides and stored

• most fat in the fed state is delivered to adipose tissue from chylomicrons and VLDLs where lipoprotein lipase cleaves fatty acids which are then taken up by the adipocytes and re-esterified

• other cells, except for blood and brain cells, can use fatty acids for energy but have a limited capacity to store fat

what are amino acids doing in the fed state?

• they are being delivered to tissues to synthesize proteins

• some gluconeogenesis occurs during the fed state because lactate from red blood cells glycolysis is recycled to the liver where it is converted to glucose through gluconeogenesis

• excess amino acids are converted to glucose or fatty acids and stored as glycogen or triglycerides

what is occurring in the postabsorptive state?

• dietary sources of fuel nutrients diminish

• must increasingly rely on endogenous sources

• glycogenolysis from the liver becomes the major source of glucose

what are the 3 changes that occur in response to decreased blood levels of glucose?

• glycogen synthesis and fat storage in the liver stop

• lactate continues to be a non-carbohydrate source of glucose

• alanine is converted to glucose in the liver

what are fatty acids doing in the postabsorptive state?

• fatty acids are released from adipose tissue and are oxidized through the tca cycle for fuel

• brain and blood cells can’t use fatty acids continue to use available glucose

• in the liver, the glycerol from the breakdown of triglycerides can also be converted to glucose

what increases as glycogen is depleted in the postabsorptive state?

• lactate

• glycerol

• alanine

how does sleep affect the postabsorptive state?

• energy decreases during sleep/rest

• you burn ~50 calories per hour

• if you eat right before you go to sleep- be in a fed state with decreased energy requirements (excess intake is stored)

• brain is a huge consumer of glucose and does not produce lactate which can replenish glucose

how much carbohydrate does the brain need each day?

110 to 145 grams each day

• quickly depletes glycogen stores

• when you sleep all night- your glycogen stores are almost completely exhausted by the morning

what occurs when liver glycogen is depleted in the fasting state?

• increase in gluconeogenesis

• amino acids from muscle breakdown provide the majority of amino acids that are converted into glucose

• lactate from red blood cells and glycerol from lipolysis still provide some additional precursors for glucose

what is a shift to gluconeogenesis stimulated by?

rises in glucagon and cortisol

• all amino acids except leucine and lysine can convert to glucose

• leucine and lysine can only be converted to fatty acids

• increase in nitrogen losses in the urine

what increases during starvation?

• lipolysis

• use of fatty acids for energy in certain tissues

• use of glycerol to make glucose

what happens to muscle cell breakdown during starvation?

it decreases but still occurs with alanine and glutamine in particular still being released to the liver

what do the kidneys do during starvation?

begin to produce some glucose through gluconeogenesis

how much glucose can be produced during starvation?

~80 grams of glucose can be produced through these methods

• amount of carbohydrates in a bagel and a banana

what does survival time with starvation depend on?

• fat stores

• activity level

• presence of illness or other stresses

• level of food deprivation

how long can an average person survive on fat stores?

3 months

how long can obese people survive on fat stores?

possibly up to a year

when does semi-starvation occur?

limited instances where no food could be consumed

• hunger strike

• illness/coma

what are endogenous sources of glucose?

• liver glycogen (send glucose to other tissues)

• muscle glycogen (can only be used in muscle)

• glycerol (breakdown of triglycerides)

• lactic acid (blood)

• glucogenic amino acids (alanine and glutamine are key)

how are cellular and hormonal controls balanced?

mtorc2 pathway at cellular level takes precedence

what do insulin and glucagon do in hormonal control of metabolism?

released from the pancreas in response to blood glucose levels

what does epinephrine do in hormonal control of metabolism?

released from the adrenal medulla in response to stress and increases heart rate and blood pressure

what does cortisol do in hormonal control of metabolism?

released from the adrenal cortex in response to stress with the goal of increasing blood sugar, regulating metabolism, and suppressing the immune system

what does growth hormone do in hormonal control of metabolism?

released from the pituitary gland in response to stress, sleep, exercise, and blood glucose levels

what does adiponectin do in hormonal control of metabolism?

produced and released from adipose cells

what is the primary source of fuel in the fed state?

glucose and fatty acids

what are the primary hormones and metabolic processes in the fed state?

insulin and synthesis through anabolic pathways

what is the primary source of fuel in the postabsorptive state?

glucose and fatty acids

what are the primary hormones and metabolic processes in the postabsorptive state?

glucagon/epinephrine, cortisol- catabolism through catabolic pathways

what is the primary source of fuel in the fasting state?

fatty acids, glucose, and some ketones

what are the primary hormones and metabolic processes in the fasting state?

glucagon, cortisol, and adiponectin- catabolism through catabolic pathways

what is the primary source of fuel in the starvation state?

ketones, fatty acids, and glucose

what are the primary hormones and metabolic processes in the starvation state?

glucagon, growth hormones, and adiponectin- catabolism through catabolic pathways