Week 9 Flashcards
Metabolism, a part of ADME:
– absorption, distribution, metabolism, excretion
– in other words: intake, transport, processing,
elimination
– and yet another way that the outside world is
embedded into our being
The totality of an organism’s chemical reactions
is called
metabolism
Metabolic pathways
- The totality of an organism’s chemical reactions
is called metabolism - This metabolism is an elaborate road map of the
chemical reactions or transformations - Metabolic pathways alter molecules in a series
of steps - These pathways are terribly complex
Humans derive energy from
the chemicals or
molecules we call food
Very often this energy is released in the form of
moving electrons (often as hydrogens) from one
molecule to the next
Losing/gaining an electron
– Losing an electron is called oxidation (LEO)
– Gaining an electron is called reduction (GER)
Energy released or required is measured in
calories
What other molecules besides glucose
can be used in cellular respiration?
- Other carbohydrates
– Proteins, although they are
not frequently used this
way - Lipids (~2X the calories or
ATP produced versus
same amount carbs or
proteins because they are
less oxidized)
Metabolism
a constant flow or continuous disequilibrium called
the vortex
Vitamin B12
-RBC formation
-Nervous system function
Absorption of
vitamin B12
- Intrinsic factor is made by parietal
cells in stomach - Vitamin B12 comes from diet or
intes6nal bacteria = extrinsic factor - Cell receptor for the intrinsic
factor+vitB12 complex used to
shuttle vitB12 by transcytosis from
the intestinal lumen across the cell
to the blood - Recall pernicious anemia situation
from Lecture 2 that arose from lack
of either the intrinsic or extrinsic
factor
Distribution to the liver!
-Send nutrients absorbed into the blood by the intestine to the liver
-Hepatic portal vein w/ nutrient rich blood -> liver for absoprtion
Liver – metabolism
- Major organ for synthesis, storage, and breakdown
– Produces many plasma proteins - e.g. Albumin, bbrinogen
– Breakdown RBC and hemoglobin - Hemoglobin → bilirubin: a component of bile
– Storage of glucose, iron, and several vitamins - Glucose polymerized into glycogen for storage (triggered by insulin)
- Fat soluble vitamins, iron
– Modify many molecules for excretion - Enzyme-catalyzed modification to make them water-soluble for elimination by kidneys (detox of drugs)
Kidneys – excretion
- Major organ for excretion of water-soluble waste
products
– Filter blood - RBC, platelets, plasma proteins, many lipids are too big to filter and stay in blood
– Reabsorb ‘good’ molecules
– Secrete ‘bad’ molecules
– Net result is urine contains waste and blood is cleansed
– Kidneys are so ekcient they can blter your entire 5L of
blood SIXTY (60) times a day!
What are hormones?
- Regulate metabolism, growth, homeostasis
- Hormones are chemical signals that promote
communication between cells, body parts, and
even individuals - Levels that are too high and too low can
drastically alter development, homeostasis,
metabolism, behavior, gestastion… you name it
Endocrine system
- Mostly comprised of glands e.g. thyroid, adrenal, pancreas
- Secretes hormones that move
through the bloodstream - Target cells have hormone receptors
that transduce the signal - Generally, results in a slow but a prolonged response, as opposed to the virtually instantaneous responses of the nervous system
- Regulates many processes including development, metabolism, and behavior
Regulation of
blood glucose by pancreatic
hormones
- Insulin – secreted when blood
glucose is high
(hyperglycemia) and
stimulates uptake of glucose
by cells (especially muscle,
liver and adipocytes) - Glucagon – secreted when
blood glucose is low
(hypoglycemia = when blood has not enough glucose) and stimulates the breakdown of
glycogen (especially in the liver and fat in adipocytes)
Blood Glucose
- Typical blood level 90-100mg/dL
- < 60mg/dL is hypoglycemia
– Confusion, fainting and loss of consciousness can occur (CNS is very sensitive to inadequate glucose since it does not store any) - > 100mg/dL is level often considered hyperglycemic and under chronic conditons leads to diabetes
- RBC also require glucose
– To make ATP and to keep them metabolically ac6ve and intact
– Have to use anaerobic pathway (fermentation) since they do not have mitochondria
– Also used to keep iron in reduced state (Fe2+) so Hb can keep carrying oxygen
(oxidize glucose to reduce iron)
– Glucose is added to donated blood!
Diagnosis of diabetes via Blood
Another common blood test and management measure for people with diabetes is glycated hemoglobin levels, commonly known as A1C. It gives a longer term measure of blood glucose levels (months) and higher levels are more problematic. (Over 200 = diabetes)
Diabetes Mellitus Epidemiology
- 1/3 to 1/5 people will be diagnosed with
diabetes at some point in their life - 18 million people in the US and 3 million in
Canada have diabetes - Almost 9% of Canadians currently have diabetes and
over a million new cases in the next 10 years in
Canada - Shortens lifespan by ~30%
- National costs associated with condi6on: >$28
Billion per year - Can be triggered in a variety of ways
What is diabetes?
- Inability to control blood glucose levels – chronic hyperglycemia = high blood glucose
- Type 1 = dependent on insulin (deficiency)
- Type 2 = cells fail to respond to insulin but have insulin
Diabetes Symptoms
– Frequent urination (glucose in the urine, also increases water excretion – b/c glucose
is an osmotically active solute) = polyurea
– Higher blood pressure (excess glucose in blood increases water dinusion from cells –
b/c glucose is an osmotically active solute)
– Unexplained change in weight
– Unusual hunger and/or thirst = polydypsia
– Blurred vision (blindness)
– Sores that heal slowly or not at all (gangrene and loss of limbs) (increase risk of infection)
– Excessive fatigue
– Numbness in extremities
-acedosis, more free fatty acids = rapid breathing, low pH, coma
- Metabolism shifts from mainly using glucose to using fats, wherein some of the
metabolic products are ketoacids and this ends up acidifying blood and tissues - Long-term enects are blindness, loss of limbs, nerve deterioration, kidney and
cardiovascular disease
Some major
consequences
of diabetes
Prevention and Treatment of Diabetes
- type I diabetes
– administer enough insulin to maintain normal
carbohydrate, fat, and protein metabolism (insulin therapy) - type II diabetes (lifestyle, meds e.g. metformin, therapies)
– maintain healthy weight, regular exercise
– dieting and exercise are usually recommended in an
attempt to utilize calories and induce weight loss (low glycemic index, high fibre diet)
– drugs may be administered to increase insulin
sensitivity or to stimulate increased production of
insulin by the pancreas - Ozempic (semaglutide) is in this category, which acts like the GLP-1 hormone. It promotes insulin release by pancreas, reduces glucose release by liver, and slows stomach emptying
