Week 5 metabolism

glycogen

storage form of glucose

red blood cells

where in the body does the TCA cycle not occur?

liver kidney and muscles

Where does the b-oxidation of fatty acids occur?

brain (during prolonged starvation) and muscles mainly

kidney and fat tissue sometimes

Where do ketone bodies get utilized

RBC

Break down of glucose, glycolysis, occurs every where besides?

lactate production, glucose—>lactate

What is produced in muscle cells during exercise and in RBC

primarily in liver and muscle, in brain/kidney/adi tissue

Where does glycogen synthesis and degradation occur

mainly in liver sometimes in kidney

Where does gluconeogensis occur?

CAT glycogen to glucose (breaking down to release energy)

ANA glucose to glycogen (using energy to make)

What counts as a catabolic process vs. what counts as a anabolic process?

availability of substrate, needs fructose to be present for process to be sped up, if none present —> process slows down or halts

Break own of fructose is dependent on?

allosteric activators and inhibitors

Feedback inhibition/activation is known as?

phosphorylation is known as COVALENT MODIFICATION OF ENZYMES can take minutes to hours to occur

What is phosphorylation known as and how long can it take?

Enzymes; enzymes needed for gluconeogensis have short half-life, everytime our body need to perform gluconeogenesis, the body creates those enzymes

What takes the longest to synthesize?

hormones

What regulates gluconeogensis?

in the pancreatic B-cells located in islet of langerhans

Where is insulin made?

Pre-pro insulin goes to ER

pre-pro is cleaved on the N-terminal

make proinsulin, go to Golgi

Insulin+C-peptide

How is insulin synthesized?

disulfide bonds

Alpha and beta chains in insulin are linked by?

it is an indicator that our pancreas are actually making insulin

Why is C-peptide useful even though it is metabolically inert

in type 2 diabetes we can determine that insulin is not being made because we do not see C-peptides in circulation. for people with this disease they usually have to inject themselves with insulin.

What is unique about type 2 diabetes

insulin works as a storage hormone

reduces blood sugar

it does this by inducing the uptake of nutrients into cells for storage to save for

later

What is the function of insulin?

Glycogenolysis

We don't want to break down glycogen because we want to actually make

glycogen stores.

● Gluconeogenesis

we don't want to make any more glucose because we already have glucose

● Ketogenesis

we don't need to make any Ketone bodies for energy because we already have

glucose

● Lipolysis

We already have excess glucose so we make triglycerides (lipogenesis)

therefore we don't need to break down our fats for energy

What process does insulin suppress and why?

Glucose stimulates the secretion of insulin from pancreatic beta cells

What is known as a major activator of insulin?

Activation of insulin by amino acids actually causes hypoglycemia.

■ For example if you were only eating proteins the amino acids in the

proteins will activate insulin release for the storage of amino acids.

Although it is only activated by the amino acids, insulin will also cause the

uptake of remaining glucose (low amount of glucose) in the blood causing

hypoglycemia.

○ Neural input

○ Gut hormones:

■ GLP

■ GIP

Name the minor activators of glucose

epinephrine

What is a minor inhibitor of insulin regulation

glucose uptake

glycogen synthesis

protein synthesis

fat synthesis

What increases due to the metabolic effects of insulin

Gluconeogensis

glycogenlysis

lipolysis

What decreases due to the metabolic effects of insulin

to facilitate the uptake of glucose (sugar) from the bloodstream into cells, particularly muscle and fat cells

What is the primary function of insulin?

receptor tyrosine kinase

What receptor does insulin bind to first to activate?

protein phosphatase-1

Insulin signaling increases __________ which leads to the metabolic effects of insulin

glucagon

What do the alpha-cells in islet of Langerhans make?

hepatic glucose output mediated by glucagon

This is when the liver performs glycogenolysis or gluconeogenesis in order to maintain blood glucose to keep the brain alive

type 1 diabetes (due to a lack of insulin production) and type 2 diabetes (due to insulin resistance).

Diabetes Type 1 vs Type 2

raise blood glucose levels

What is the major function of glucagon

glycogenoLYSIS:

glucagon stimulate the breakdown of glycogen into glucose in the liver. Glycogen is a stored form of glucose, and when glucagon is released, it prompts the liver to convert glycogen back into glucose and release it into the bloodstream.

What does glucagon stimulate

encourages the liver to produce glucose from non-carbohydrate sources, such as amino acids and glycerol. This process is called gluconeogenesis, and it helps raise blood glucose levels when dietary sources of glucose are insufficient.

What does glucagon promote?

Glycolysis is the breakdown of glucose for energy within cells. Glucagon inhibits this process, ensuring that glucose is not excessively used by the cells but is instead made available in the bloodstream for other tissues and organs that need it.

What does release of glucagon inhibit?

brain

What organ does glucagon help the most?

decreases

Does insulin increase or decrease blood glucose levels

brings up blood glucose to a stable level

when blood glucose is low DURING FASTING pancrease releases glucagon

Does glucagon increase or decrease blood glucose levels

glucagon's primary function is to raise blood glucose levels when they are low, in contrast to insulin, which lowers blood glucose levels when they are elevated

How do insulin an glucagon contrast?

activation of protein kinase A

What does glucose stimulate in order to get a cellular response

when blood glucose lvels are low in order to increase it

When is glucagon activated?

G-protein coupled receptor to actiate cyclic-amp

Glucagon binds to a ____________ in order to activate __________

Amino acids stimulate glucagon, glucagon then stimulates the liver to release glucose

What are the major stimulators of glucagon?

insulin causes hypoglycemia because of a protein based diet.

What can too much insulin cause?

glucose and insulin supresses glucagon

What inhibits the regulation of glucagon release?

neural stress can lead to the release of epinephrine and cortisol

What are minor activators of glucagon release?

cortisol stimulates gluconeogensis

cortisol stimulates glucagon to mobilize fatty acids during stress

What is the role of cortisol in stimulating glucagon

IN FED STATE:

people with type 1 diabetes were injected with insulin. the insulin caused drop of blood glucose

those injected with glucagon: ■ There was a immediate/drastic increase of blood glucose levels. This happened because glucagon causes hepatic glycogenolysis and hepatic gluconeogenesis

What does glucagon release in Type 1 diabetes create?

high protein diet causes INSULIN to uptake of amino acids from blood as well as UPTAKE OF GLUCOSE —> low blood glucose hypoglycemia

Amino acids also stimulate GLUCAGON

glucaon release hepatic glucose through two pathways

How do glucagon and insulin work together when stimulated by amino acids (high protein diet)

25% in liver is finite, not much space in livre for glycogen storage

skeletal muscle contins 75%

How much of glycogen do we have stored?

24 hours without excercise

How long does it take to completely be depleted of glycogen stores?

dietary

glycogenolysis

gluconeogensis

What are the three sources of glucose in the blood

low while sleeping and increases a after meals

When is dietary glucose the highest in your body

spikes when dietary glucose is used up, spikes between meals

When is glycogenolysis the highest?

glycogenolysis; stimulated by glucagon

What source of glucose spikes during sleeping/fasting?

glycogenolysis

What does epinephrine simulate in muscle cells to be used by muscle cells

gluconeogensis is high when waking up when cortisol levels are high

When is the production of glucose the highest

increases:

glycogenolysis

gluconogensis

fatty acid oxidation

ketogensis

uptake of amino acid

What are the metabolic effects of glucagon release

glycogenesis

What does glucaon release inhibit/decreases

brain and tissues

What systems use glucose right after being fed/exogenous

blood glucose supplied by glycogen and hepatic gluconeogensis

• glucose used by brain and tissues but not liver or muscles or adipose

What occurs between the hours of 4-16

blood glucose supplied by hepatic gluconeogenesis

and glycogen

What occurs during hour 16-30 of starvation

blood glucose obained by hepatic and renal gluconeogensis

glucose used by brain, RBC and not much by muscles

What occurs between 2-24 days of starvation

uses glucose and ketone bodies

Where does the brain get energy from after days of starvation?

neuroglycopenia symptoms

headache confusion

slurred speech

seizures death and coma

adrenergic symptoms

anxiety palpitation

tremor sweating

What does low blood glucose lead to

insulin and glucose GO UP

glucagon GOES DOWN

What happens when you have a high carb meal

glucaon and nitrogen rise

glucose stays steady

insulin drops

What happens when you eat a high protein meal

glucneogensis as it requires atp to make glucose

Which reaction is favored when theres an abundance of atp

glycolysis

ATP acts an as inhibitor of

gluconeogenesis as this process requires atp to continue

AMP is an negative regulator of

insulin as there is no glucose for uptake

during hypoglycemia what hormone should be supressed

glucose used to

• make glycogen

• acetyl coa to make fatty acids

• amino acids

During the absorbtive state, what happens in the liver

Use glucose to make:

• lactate and ATP

• pentose and NADPH

During the absorbtive state, what happens in RBC

use glucose to make

acetyl COA for the TCA cycle

in this cycle it makes h2o, co2, and ATP

During the absorbtive state, what happens in the peripheral tissues

glucose makes:

Glycogen

● Lactate + ATP

● h2o, co2, and ATP (in TCA)

During the absorbtive state, what happens in skele muscle

glucose makes:

glycerol 3-p

During the absorbtive state, what happens in adipocytes

use glucose to make

acetyl coa for TCA cycle

During the absorbtive state, what happens in pancreas

glucose AND faty acids used to make

acetyl coa for tca cycle

During the absorbtive state, what happens in heart

hepatic blood glucose

what maintains blood glucose when youre fasting

tyrosine kinase

Insulin use what type of receptor

g-coupled protein receptor

what receptor does glucagon use

protein phosphatase 1

insulin stimulates

glucagon adds a phosphate and insulin removes it

what does glucagon and insulin do to phosphates

insulin

What is the main thing that surpresses ketosis

cortisol neural stress and epinephrine

What are the three minor stimulators of glucagon

fatty acids

Glucagon is also known to mobilize what to the brain?

high glucagon low insulin

during periods of fasting we have high ____________ low ___________

glucagon release

When we have high insulin and high glucose it suppresses

up

When we have low insulin and low glucose, glucagon goes

70-100

What is considered normal fasting glucose

gluconeogenesis, make new glucose

glucaon and cortisol promote what?

glycogenolysis, break down of gluse when body needs glucose but no glucose present

what do norepinephrne and glucagon stimulate

gluconeogensis glycogenolysis

Cortisol will very strongly stimulate ____________ but not ___________

glycogenolysis and not gluconeogenesis

Epinephine will very strongly stimulate ____________ but not ___________

glycogen and gluconeogenesis

What are the two ways liver can pump out glucose into the body

glucagon spikes

if injected with insulin what happens in people with type 1 diabetes

glycogen

what form of glucose is finite in the body

glut 4

which glut transporter is insulin sensitive

insulin

pancreas will produce what in response to ingested glucose