MCAT Biochemistry Chapter 12: Bioenergetics and Regulation of Metabolism

ATP energy under standard conditions (ΔG˚) ATP energy under modified standard conditions (ΔG˚') i.e. pH = 7, and with excess magnesium

-55kJ/mol -30.5kJ/mol

Primary source of energy, well-fed vs fasting: liver

AA; FA

Thyroid hormone effect on fats:

accelerate cholesterol clearance from blood

After storing glucose (glycogenesis), the the fate of excess liver glucose is...

acetyl-CoA → putting it into fatty-acid-synth → made in triglycerides → released into VLDL

Why is glucagon not considered a major mobilizer of fats?

because it only acts on THE LIVER to release fats, NOT ON THE ADIPOCYTES (where most fat is stored!)

Enthalpy (ΔH)

change in HEAT of a system; is the same thing = Q at constant P/V

If a rxn at the end has more reactants than products , then the ΔG of the fwd rxn is...

(+)

The sign of ΔG and E (electromotive force) for spontaneous oxidation-reduction reactions are...

(-) & (+)

In one day, a person uses ____% of their body weight in ATP, but at one time possesses only ___g of it

90%, 50g; note this is possible because ATP is constantly recycled

Postabsorptive State (Fasting)? what hormone levels are high? what processes are active?

AKA: - glucagon, cortisol, norepinephrine, & growth hormone oppose the actions of insulin - in the liver, glycogen degradation & the release of glucose into the blood are stimulated - hepatic gluconeogenesis is also stimulated by glucagon, but the response is slower than that of glycogenolysis - whereas glycogenolysis begins almost immediately at the beginning of the postabsorptive state, gluconeogenesis takes about 12 hrs to hit max velocity - the release of amino acids from skeletal muscle & fatty acids from adipose tissue are both stimulated by the decrease in insulin & by an increase in levels of norepinephrine - once carried out in the liver, amino acids & fatty acids can provide the necessary carbon skeletons & amino acids required for gluconeogenesis glucagon/cortisol/epinephrine/norepinephrine up & insulin DOWN → liver, muscle, adipose → NEGATIVE INSULIN'S EFFECTS → liver degrades glycogen (fast); gluconeogenesis begins (slow, after 12h); → FA release from adipose + AA release from muscle (low insulin) and go to liver for GNG/𝛽-ox

Prolonged Fasting (Starvation)? what hormone levels are high? what processes are active?

AKA: - levels of glucagon & epinephrine are markedly elevated - increased levels of glucagon relative to insulin result in rapid degradation of glycogen stores in the liver - as liver glycogen stores are depleted, gluconeogenesis activity continues to play an important role in maintaining blood glucose levels during prolonged fasting - after 24 hours, gluconeogenesis is the predominant source of glucose for the body - lipolysis is rapid resulting in excess acetyl-CoA that is used in the synthesis of ketone bodies - once levels of fatty acids & ketones are high enough in the blood, muscle tissue will utilize fatty acids as the major fuel & the brain will adapt to using ketones for energy - after several weeks of fasting, the brain derives approx. 2/3 energy of ketones & 1/3 from glucose - the shift from glucose to ketones as the major fuel reduces the amount of essential amino acids that must be degraded to support gluconeogenesis, which spares proteins that are vital for other functions - cells that have few, if any mitochondria, like RBCs, continue to be dependent on glucose for their energy epinephrine/glucagon high → glycogen rapidly lost → GNG dominates at 24h → FA release → 𝛽-ox → 𝛽-ox acetyl-CoA used for ketone bodies (spares proteins from going to GNG) → muscles use FA → brain uses 2/3 ketones 1/3 glucose

Body Mass Index (BMI)

BMI = mass/height^2 (kg & m); normal = 18.5-25, 30+ obese

The type of system that smaller biological systems are considered (e.g., cell) are: (open/closed/isolated)

CLOSED (energy change only, no matter lost)

In general, hormones control metabolism by producing/removing...

COVALENT BONDS on enzymes (to phosphates!)

During the fasting state, what are the insulin levels? epi levels? what do these activate? where?

Causes decreased levels of insulin and increased epi that activates hormone-sensitive lipase (HSL) in fat cells, allowing fatty acids to be released into circulation HSL is activated when the body needs to mobilize energy stores, and so responds positively to catecholamines, ACTH. It is inhibited by insulin

Primary source of energy, well-fed vs fasting: cardiac muscle

FA; FA/ketones

The levels of thyroid hormones change based on:

NOTHING, they're basically constant

The macromolecule that does not significantly contribute to body weight is? The mass of 2 macromolecules in our body is relatively stable? The macromolecule that contributes most to weight fluctuations is?

Not much contribute = nucleic acids Stable = Carbs and proteins Weight fluctuations = lipids

The type of system biological beings overall are considered are: (open/closed/isolated)

OPEN (exchange matter/energy)

The MAIN level that controls insulin secretion is:

PLASMA LEVELS OF GLUCOSE; above 5.6mM (100mg/dL), insulin secretion PROPORTIONAL to glucose levels

The MAIN level that control glucagon secretion is:

PLASMA LEVELS OF GLUCOSE; hypoglycemia demands it, while hyperglycemia is the opposite (insulin!)

In general, insulin causes adipocytes to do WHAT with fatty acids?

Suppress the release of fatty acids from adipose tissue

How T4 and T3 release

T4 is a precursor; T4 → T3 via deiodonases (de-iodine-ize it!)

The brain's use of glucose/energy compared to rest of body

WAY DISPROPORTIONAL; brain is 2% weight, but takes 15% of blood, 20% of O2, 25% of glucose

As a reaction approaches equilibrium, ΔG approaches...

ZERO; no energy release when there is no reaction occurring!

Glucagon? secreted by what? function?

a peptide hormone secreted by 𝛼-cells of pancreas; signals release of glucose THROUGH SECONDARY MESSENGERS (PRIMARILY OF LIVER HEPATOCYTES) + glycogenolysis, gluconeogenesis & slows unecessary glycolysis & glycogenesis Glucagon, the "hormone of starvation," promotes formation of glucose and fatty acids

Insulin? what is it secreted by? what processes does it activate in terms of glucose?

a peptide hormone secreted by 𝛽-cells of pancreas; signals uptake of glucose + glycolysis, glycogenesis, and slows uneccessary GNG & glycogenolysis Insulin, the "hormone of excess," promotes the storage of glucose, fatty acids, and amino acids

Catecholamines? types? function?

amino acid-derived hormones of the adrenal medulla (NOREPINEPHRINE, EPINEPHRINE): INCREASE glycogenolysis enzymes in liver/muscle, INCREASE lipolysis via HSL for 𝛽-ox and GNG

How RBCs get energy

anaerobic glucose use ALWAYS (never changes) Red blood cells rely on glucose for energy and convert glucose to lactate. The brain uses glucose and ketone bodies for energy. Adipose tissue uses fatty acids and glucose for energy.

Relationship between insulin & glucagon

antagonistic; enzymes phosphorylated/activated by insulin have the opposite done by glucagon; they end up with certain 'feedback' on each other where too high of 1 makes the other secrete in the end

During Weight gain, how does BMR change/not change?

as you gain weight, BMR increases too; this occurs until equilibrium is re-attained and your weight stabilizes One surprising thing about metabolism is this: the more you weigh, the faster your metabolism will be. This happens because your body must work harder to maintain itself. That is also why it is easier to lose weight in the beginning of a fat loss/weight loss program. Since your BMR is closely linked to your lean body mass, any changes will affect the number of calories you burn. ... Conversely, if you lose some lean body mass as a result of going on a strict caloric deficit diet, your BMR will decrease

Respiratory Quotient (RQ) for: carbs = fats = at rest =

carbs = 1.0 fats = 0.7 at rest = 0.8; means carbs (1.0) and fats (0.7) are being consumed The Respiratory Quotient value indicates which macronutrients are being metabolized, as different energy pathways are used for fats, carbohydrates, and proteins. If metabolism consists solely of lipids, the Respiratory Quotient is 0.7, for proteins it is 0.8, and for carbohydrates it is 1.0.

Most tissues use glucose as their primary energy source while well-fed, except for...

cardiac muscle; uses mostly FAs

Entropy (ΔS)

change in disorder/energy dispersion of a system in J/K

When exercise is short-lived, muscle uses this for energy... (2)

creatine phosphate (gives Ps to ADP) & anaerobic respiration via glycogen

Energy amount in fats vs carbs vs proteins vs ketones & the relative space they take up

fats: 9kcal/g, the rest: 4kcal/g; all molecules roughly the same size

Postprandial State (Absorptive/Well-fed)? what processes (catabolism/anabolism) are active? insulin levels? glucagon levels? when is this after eating?

for 3-5h after eating; ANABOLISM is generally active to store fuel: insulin rises → liver, muscle, adipose respond → GLUCOSE ENTRY → glycogen synthesis; FA/triglyceride synthesis; protein synthesis

Counterregulatory Hormones (4):

glucagon, cortisol, epinephrine, norepinephrine; THE 4 HORMONES THAT OPPOSE INSULIN'S ANABOLIC ACTION and are released in the postabsorptive state

The adrenal cortex produces hormones called '______________', whereas the medulla produces ones called '______________'

glucocorticoids; catecholamines

When exercise is moderate exercise (1-3h), skeletal/cardiac muscle use this for energy...

glucose, FAs

Primary source of energy, well-fed vs fasting: adipose tissue

glucose; FA

Primary source of energy, well-fed vs fasting: resting skeletal muscle

glucose; FA/ketones

Primary source of energy, well-fed vs fasting: RBCs

glucose; glucose

Primary source of energy, well-fed vs fasting: brain

glucose; glucose/ketones

In response to insulin, the liver slows glycogenolysis/gluconeogenesis by stopping the enzymes...

glycogen phosphorylase + G-6-Phosphatase

The glycerol phosphate required for triacylglycerol synthesis comes from glucose that is metabolized in adipocytes as an alternative product of ___________

glycolysis

How the 𝛽-cells of pancreas know to secrete insulin:

high levels of blood glucose mean high metabolism of glucose in pancreas → high ATP conc'n → Ca2+ released in cell → signals exocytosis of insulin

Leptin (hormone)? function?

hormone secreted by fat that suppresses orexin (decreases appetite); your genetics determine how much leptin you produce + its receptors, affecting obesity rates

When hypoglycemia (<70mg/dL) is sensed, the brain's ______________ triggers the release of glucagon/epinephrine for glucose

hypothalamus

ATP phosphoryl transfer + coupling (Hess's Law)

if you can add up 2 reactions (ATP hydrolysis + something else) into a total reaction, you can apply Hess's Law and sum up the total ΔG; IF NEGATIVE, THE RXN IS SPONTANEOUS, AND YOU CAN MAKE A NON-SPONT RXN SPONTANEOUS!

Difference b/t when insulin-response & -unresponsive tissues store glucose

if you respond to insulin, you store glucose at HIGH CONC, and if you don't you store it AT ALL CONC's

Thyroid hormone effect on carbs:

increase glucose from intestine, accelerate carb metabolism

Effect of insulin on carbs (liver/muscle/adipose) (4):

increase glucose uptake, most tissues: increase glycolysis, increase glycogenesis, decrease glycogenolysis, decrease gluconeogenesis AKA: The major effects of insulin on muscle and adipose tissue are: (1) Carbohydrate metabolism: (a) it increases the rate of glucose transport across the cell membrane, (b) it increases the rate of glycolysis by increasing hexokinase and 6-phosphofructokinase activity, (c) it stimulates the rate of glycogen synthesis and decreases the rate of glycogen breakdown.

Effect of insulin on fats (liver/adipocytes) (5):

increase triglyceride uptake, increase lipoprotein lipase (takes fat out of blood), increase lipogenesis (i.e. FA synth/trigly synth), decreases lipolysis, decreases ketone formation

Effect of insulin on amino acids (3):

increase uptake in muscles, increases protein synth, decreases proteolysis

Glucagon activates/inhibits these things/enzymes via secondary messengers (5):

increases glycogenolysis (glycogen phosphorylase, inhibits synthase), increases gluconeogenesis (pyruvate carboxylase + PEP carboxykinase, F-1,6-BP), increases ketogenesis, increases lipolysis (HSL in liver), DECREASES lipogenesis

T3 (triiodothyronine)

increases metabolism and basal metabolic rate (BMR) produces a rapid increase in metabolism that is SHORT

When your heart is failing, cardiac metabolism changes by...

increasing glucose use, decreasing FA use

How cortisol causes weight gain

is causes glucose release, but NOT AS MUCH FAT (lipolysis); high glucose ending up in blood causes insulin release → insulin causes adipocyte lipogenesis → fat!

The effect of cortisol on nervous tissue (3)(glucose related)

it increases glucose availability to it in 3 ways: 1) inhibits glucose uptake in MOST tissue (muscle/lymph/fat) & 2) increases liver gluconeogenesis from AA + release, 3) enhances glucagon/epinephrine/ norepinephrine/others to release MORE glucose Under stressful conditions, cortisol provides the body with glucose by tapping into protein stores via gluconeogenesis in the liver. This energy can help an individual fight or flee a stressor. However, elevated cortisol over the long term consistently produces glucose, leading to increased blood sugar levels

Why can muscle not release glucose to the blood (/why must it use glycogenolysis glucose itself)?

it lacks G-6-Phosphatase that would chop off that P blocking glucose from exiting into blood; all of it must be used by the muscle itself AKA: Because of its mass, muscle contains almost four times as much glycogen as the liver. Muscle glycogen is not directly available as a source of blood glucose because muscle lacks glucose-6-phosphatase. During muscular activity, glycogen is converted to lactate and then into blood glucose in the liver.

The enzyme ______________ in the capillaries adipose tissue is activated by ______________; it releases fatty acids that are taken up by the adipose tissue, which are then re-esterified

lipoprotein lipase; insulin

The MAJOR zones of the body that perform metabolism & they do so in their own unique ways are (5):

liver, skeletal muscle, cardiac muscle, brain, adipocytes

The 2 types of cells insensitive to insulin

nervous, RBCs

Tissues that DO NOT increase glucose uptake w/ insulin (5)

nervous, kidneys, intestinal mucosa, RBCs, 𝛽-cells of pancreas

How nervous cells get energy

oxidize glucose → CO2 + water in WELL-FED & FASTING STATES (only changes after LONG fast) Just like other cells in the body, brain cells use a form of sugar called glucose to fuel cellular activities. This energy comes from the foods we consume daily and is regularly delivered to brain cells (called neurons) through the blood

After a large meal, most of the energy needs of the liver are met by...

oxidizing excess amino acids How does the liver meet its own energy needs? α-Ketoacids derived from the degradation of amino acids are the liver's own fuel. In fact, the main role of glycolysis in the liver is to form building blocks for biosyntheses. Furthermore, the liver cannot use acetoacetate as a fuel, because it has little of the transferase needed for acetoacetate's activation to acetyl CoA. Thus, the liver eschews the fuels that it exports to muscle and the brain.

What is the ultimate event that happens FIRST when metabolic changes occur?

phosphorylation/dephosphorylation of the enzymes that control metabolism

T4 (thyroxine)

produces a latent increase in metabolism that lasts LONG

Proteins with THIS are well-suited for transporting electrons:

prosthetic groups containing Fe-S

Flavoproteins (structure: 2, uses: 5)

proteins that have 1) a modified vitamin B2 (riboflavin) and are 2) ultimately derived from nucleic acids; e.g., flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN); 1) electron carriers for ETC & chloroplasts, 2) activate other vitamin B derivatives 3) coenzymes in the oxidation of FA, 4) decarboxylation of pyruvate, 5) reduction of glutathione

Tissues that increase glucose uptake w/ insulin:

resting skeletal muscle, adipose Insulin mediates glucose uptake into adipose tissue and skeletal muscle through GLUT4 glucose transporters. Vesicles containing GLUT4 glucose transporters are mobilized to the plasma membrane by insulin stimulation, thereby effecting glucose transport into the cell. The major effects of insulin on muscle and adipose tissue are: (1) Carbohydrate metabolism: (a) it increases the rate of glucose transport across the cell membrane, (b) it increases the rate of glycolysis by increasing hexokinase and 6-phosphofructokinase activity, (c) it stimulates the rate of glycogen synthesis and decreases the rate of glycogen breakdown. (2) Lipid metabolism: (a) it decreases the rate of lipolysis in adipose tissue and hence lowers the plasma fatty acid level, (b) it stimulates fatty acid and triacylglycerol synthesis in tissues, (c) it increases the uptake of triglycerides from the blood into adipose tissue and muscle, (d) it decreases the rate of fatty acid oxidation in muscle and liver. (3) Protein metabolism: (a) it increases the rate of transport of some amino acids into tissues, (b) it increases the rate of protein synthesis in muscle, adipose tissue, liver, and other tissues, (c) it decreases the rate of protein degradation in muscle (and perhaps other tissues).

Glucagon's interaction with proteins/amino acids:

secreted in response to HIGH PROTEINS/AAs (especially basic) in blood!

Ghrelin (hormone)? function?

secreted in response to impending meal (SMELL++, sound, taste, sight) increasing appetite; stimulates orexin

ADP energy release compared to ATP? AMP hydrolysis ΔG?

similar values! ADP has P-repulsion and hydrolysis resonates P too -9.2kJ/mol; WAY smaller than ATP & ADP

Which hormone classes act SLOW/LONG? steroid, peptide, or AA?

steroid (e.g., cortisol) & amino-acid derived (e.g., thyroid)

Glucocorticoids? found where? function?

steroid hormones of adrenal cortex (e.g., cortisol) that activate in FIGHT-OR-FLIGHT: stimulate GLUCOSE + FA release Glucocorticoids are secreted in response to ACTH, which is secreted from the anterior pituitary gland during times of stress. Glucocorticoids increase blood glucose levels, which provide readily available energy for your body cells. The adrenal cortex also secretes sex hormones

Orexin (hormone)? function?

stimulated by ghrelin AND hypoglycemia; FURTHER increases appetite; involved in increasing alertness (sleep-wake)

Basal Metabolic Rate (BMR)? factors affecting this?

the amount of energy your body consumes for just existing; can be measured by putting people in a giant calorimeter (expensive so other methods ++) age, growth, height, % lean tissue, fasting, starvation, malnutrition, fever, hormones (thyroxin), sleep

The fuel choice used for active muscle depends on...

the duration of exercise and the type of muscle

Water weight can be rapidly adjusted via...

the endocrine system + kidneys (pee out)

Glucagon's primary target is...

the liver hepatocytes (signals release of glucose)

Internal Energy (U)

the sum of all energies b/t & within atoms in a system (vibration, rotation, linear motion, chemical energy)

Respirometry (biochem)

the technique to measure Respiratory Quotient (RQ) values come from the COMPLETE COMBUSION (oxidization) of a fuel The Respiratory Quotient value indicates which macronutrients are being metabolized, as different energy pathways are used for fats, carbohydrates, and proteins. If metabolism consists solely of lipids, the Respiratory Quotient is 0.7, for proteins it is 0.8, and for carbohydrates it is 1.0.

Why are FAs not used as fuel for the brain?

they cannot cross the blood-brain barrier!

Why some people can eat more but not gain weight

they have a proportional increase in BMR that can make-up for increase intake!

In general when ATP is hydrolyzed, the P usually goes through a ___________ transfer which means?

through a Phosphoryl Group Transfer; i.e. it goes onto another molecule, which ACTIVATES or DEACTIVATES it

RQ for humans changes when? how?

under stress, starvation, exercise The Respiratory Quotient value indicates which macronutrients are being metabolized, as different energy pathways are used for fats, carbohydrates, and proteins. If metabolism consists solely of lipids, the Respiratory Quotient is 0.7, for proteins it is 0.8, and for carbohydrates it is 1.0. During exercise = increases from baseline (0.8) close to 1.0, as glucose metabolism increases (which has RQ = 1)

Which hormone class acts FAST: fat or water soluble? steroid, peptide, or AA?

water-soluble peptides (e.g., insulin)

Why must LARGE changes be made to lose weight, but not gain?

when only small changes are made (small increases in exercise, small decreases in food intake), the body adjust by changing BMR to match! There is a difference threshold for exercise/intake that is LARGER than the needed to gain weight

Insulin triggers adipose tissue to uptake x and release y

x = glucose, y = triglycerides (via VLDL & chylomicrons)

When exercise is LONG (3+ hours), x becomes depleted in skeletal/cardiac muscle and y must be used

x = glycogen, y = fatty acids

ATP turnover in our body is x__________ per day

x1000 The ATP turnover time, as defined as the ratio between ATP content and ATP production

Gibbs-entropy-ethalpy equation

ΔG = ΔH - TΔS; the sign of G predicts the spontaneity of reaction (and actually direction; whether rxn is spont in fwd or rev)

Standard Free Energy (ΔG˚)

ΔG at 1M, 1atm, 25˚C

First Law of Thermodynamics Equation (for biological systems)

ΔU = Q - W, but there is no W since P/V don't change! Therefore ΔU = Q Work = P*V and is the area contained in the PV graph