Pathophysiology: Cell Metabolism

ATP

adenosine triphosphate, the body’s main source of energy largely synthesized from carbohydrates

Glycolysis, Citric Acid Cycle, Oxidative Phosphorylation

What are the three steps of carbohydrate metabolism?

Anabolic Reaction

requires energy (ATP)

-building things up

-sugar → large carbohydrates

Catabolic

release energy (ATP)

-breaking things apart

-large carbs → sugars

energy carrier, third

ATP is an ______ ______. The energy needed to make reactions go are found in the medial oxygen and _____ phosphate in the tail’s third phosphate group.

Enzymes

catalyzes metabolic reactions

-are proteins 99.9% of the times, can also be ribozymes (RNAs)

-structure dictates function

Substrate-specific

The active site of a molecule is ________-_______, meaning one enzyme fits in one specific type of substrate. This is good because it prevents improper functioning of enzymes. The shape of the active site is determined by what amino acids make up the protein.

Activation Energy

the energy required for a reaction to take place

-to reach this in a time-effective manner, you need an enzyme

Small Molecule Binding

Regulates enzymes

-without them, these reactions would occur at random times and drain the cell/body of energy

Cofactors

promote enzyme function by binding to the protein and stabilizing its structure

-ex ions (Mg, Fe) and small molecules

Coenzymes

promote enzyme function

-ex coenzyme A in metabolism

Competitive Inhibitor

binds in the active site, blocking the substrate from binding and halting enzyme function

Non-Competitive (allosteric) Inhibitor

binds outside the active site, changes the shape of the active site and prevents the substrate from binding

Cytoplasm and mitochondria

Production of energy occurs in the _____________ and ___________

stored or used immediately

Glucose must be ________ or _______ ________

Glycogen

stored form of glucose found most often in the liver

Glycolysis

a set of 10 chemical reactions that start with glucose + 2 ATP and ends with pyruvate + electrons + 4 ATP

-net 2 ATP

-electrons are carried by NADH to ETC

Pyruvate, Citric Acid Cycle

The goal of glycolysis is not to produce ATP but rather to produce _________, which is the molecule required to start the ________ ______ ________

Allosteric Regulation

Binding of small molecules outside the active site

-Does the reaction happen?

-At what speed does it happen?

Products

Enzymes in glycolysis are regulated by __________ of glycolysis

Hexokinase

binds to glucose very tightly and is good for generating energy with very little glucose in the body; means cells can still undergo glycolysis if glucose is in low supply

-Answers the question of does glycolysis happen?

Liver Hexokinase

the exception to the role of hexokinase, does not bind well to glucose because glycogen is produced in this organ

PFK

-inhibited by ATP, activated by ADP

-more active when there is less energy in the cell

-ATP binds to allosteric site, blocking PFK and halting glycolysis

-ADP activates PFK and kick starts glycolysis

-Answers the question of “how fast does glycolysis occur”

ATP and acetyl-CoA

Pyruvate kinase is inhibited by?

-done to prevent pyruvate from being turned into lactate and burning muscle, no need to finish glycolysis if these are already in excess

Fat

Glycolysis is sometimes inhibited when ___ can be used as an energy source

-___ metabolism = acetyl CoA production, blocks glycolysis

Oxygen

Glycolysis can also be inhibited by _______

Aerobic Metabolism

will only happen if oxygen is in the cell, proceed to Citric Acid cycle in mitochondrial lumen

Anaerobic Metabolism

no/low oxygen present

proceeds to fermentation or lactic acid production

Fermentation

form of anaerobic metabolism where acetaldehyde is produced and turned into ethanol, releasing CO2

-should not happen in humans

-common in beer and wine making

Lactic Acid Production

form of anaerobic metabolism that is more common in humans, results in the burning of muscles

Recycle electron carriers

The goal of anaerobic metabolism is to _____ ______ ______ that can pick up the electrons produced during glycolysis and eventually get into aerobic respiration

Lactate Dehydrogenase

converts pyruvate to lactate → lactic acid

Alcohol Dehydrogenase

pyruvate → acetaldehyde → ethanol

releases carbon dioxide

Oxygen Debt

not enough oxygen to function through the Citric Acid Cycle

-oxygen required to restore energy stores

-energy to convert lactate back to glucose

Gluconeogenesis

What process helps fight the oxygen debt by converting lactate into glucose within the liver?

Requires energy

Citric Acid Cycle

occurs in the lumen of the mitochondria, goal is to get electrons to the electron transport chain

-in: pyruvate and acetyl-CoA

-out: electrons, GTP, CoA

-components of this cycle are used elsewhere in the cell, like citrate in semen

Electron Transport Chain

proteins embedded in the inner mitochondrial membrane

-electrons are passed from one protein complex to the next, decreasing energy with each passage

-H+ ions pumped across the membrane, and electrons are accepted by oxygen

-generates 32 ATP

CoQ Deficiency

metabolic disease caused by the lack of coenzyme Q synthesis

-loss of electron shuttle in ETC, preventing the cell from making all of the ATP it needs

-results in the breakdown of skeletal muscles

-can be treated with CoQ supplements or riboflavin

Chronic Lactic Acidosis

metabolic disease caused by a genetic deficiency in ETC subunits, rendering them unable to function

-causes a build-up of lactic acid in tissues due to lack of respiration

-results in tissue acidification

-pH can be regulated by IV fluid

Gluconeogenesis

making new glucose, reverse synthesis of glucose from pyruvate or other intermediates

-while most cells just get their glucose from the blood, some tissues rely heavily on glucose and need to perform this process

ex brain, muscles, liver

Glycogen

storage form of glucose found in the liver, separate stores can also be found in the muscles and brain

-does this to prevent high blood glucose, which can lead to many conditions

-allows for quick glucose mobilization when necessary

Glycogen Synthase

adds new glucose molecule to growing carbohydrate chain

Glucagon

the hormone that mediates the release of glucose from glycogen

Glycolysis, gluconeogenesis, pentose phosphate pathway

Glucose-6-Phosphate has three fates…

Pentose Phosphate Pathway

generates ribose and NADPH, support production of antioxidants and synthesis of other biomolecules like DNA or RNA

Liver and pancreas

What organs regulate blood glucose?

Insulin and glucagon

What hormones regulate blood glucose?

Type 1 Diabetes

diabetics that are unable to produce insulin or an adequate amount of insulin

Type 2 Diabetes

diabetics have no response to insulin

Proteins

_________ can contribute carbons to the Citric Acid Cycle if needed, however, this is a last ditch effort

Lipid Metabolism

occurs in the mitochondria once per two carbons, which go to produce Acetyl CoA through beta oxidation

-also releases electrons for the ETC

-carnitine acts as a carrier across the mitochondrial membrane

FADH2 and NADH

These are also produced via fatty acid oxidation

2 ATP

One molecule of FADH2 results in _ ATP

3 ATP

One molecule of NADH results in _ ATP

Diabetic Ketoacidosis

can occur in Type I Diabetics when their cells don’t get a signal about there being sugar in the blood, preventing them from taking it out of the bloodstream. The cells then switch to fatty acid metabolism, producing ketones

-can cause hyperglycemia, hyperketonemia, acidosis, nausea, vomiting, abdominal pain, swelling of the brain, coma, and death

Glucagon

________ is also in excess in diabetic ketoacidosis, meaning type I diabetics cannot modulate or metabolize glucagon. Their cells use triglycerides or amino acids for energy. Also stimulates conversion of fatty acids to ketones, resulting in the “sweet breath” some diabetics have

Ammonia

an important enzyme substrate converted to glutamate, glutamine, asparagine

-used in amino acid and nucleotide synthesis

Transamination

amines transferred from one molecule to another, substituting for a ketone

-requires a variety of coenzymes like pyridoxine and pyridoxal phosphate

Essential Amino Acids

amino acids that cells cannot synthesize, must be consumed dietarily

Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine

What are the essential amino acids?

conditional amino acids

In times of stress, we must also consume _________ ____ ______ like arginine, cysteine, glycine, and glutamine

Urea Cycle

important for amino acid degradation

-produces urea from ammonia, which is not good for the body

-required to clear ammonia from the blood, typically through urination

-coupled with the TCA cycle