Endocrinology/Metabolism/Nutrition Flashcards
What does insulin do to the rate of facilitated diffusion of glucose and by what mechanism?
It increases it by increasing the activity and amount of hexokinases and glucokinases.
What does hexokinase/glucokinase do?
Phosphorylation of glucose so it can’t leak back out of the cell during glycolysis
What are the effects of the hormones epinephrine and glucagon on glycogen?
Stimulate glycogen breakdown through activation of phosphorylase and prevent glycogen synthesis by increases cytosolic levels of cAMP
Where is glucagon released from?
Pancreatic alpha cells
Each mole of glucose can produce how much ATP?
38 moles
What are the steps of glycolosis and what are the final products?
Glucose –> glucose-6-phosphate –> fructose-6-phosphate –> fructose 1,6 diphosphate –> DHAP/G3P –> 1,3 - DGP –> 3-PG –>2-PG –> PEP –> pyruvate
Final products:
2 pyruvate
2 ATP
4 H
What are the steps to the Kreb’s Cycle and what are the final products
acetyl coA ->
citrate –> isocitrate –> alphaketogluterate –> succinol coA –> succinate –> fumarate –> malate –> oxaloacetate
Final products:
4 CO2
16 H (NADH and FADH2)
2 ATP
What are the products of oxidative phosphorylation?
30 ATP (by chemiosmotic mechanism)
4 ATP (from NADH and FADH2)
How is cellular respiration regulated? What are 3 mechanisms?
By concentrations of ATP and ADP.
1. Imp enzyme in glycolysis is phosphofruktokinase which is inhibited by ATP and promoted by ADP.
2. Citrate inhibits phosphofructokinase allowing kreb’s cycle to catch up to glycolosis
3. Finate amount of ADP so can overproduce ATP
Why is the pentose phosphate pathway important (2 reasons)?
- It can break down glucose and make energy independent of the enzymes of the Kreb’s cycle.
- Means of producing fat from carbs.
What is a lipoprotein and list 4 types and their differences?
A predominent plasma lipid in the fasting state containing various combinations of triglycerides, cholesterol, phospholipids, and protein.
- VLDL - high triglycerides, moderate cholesterol and phospholipid
- IDL - VLDL but some triglycerides are removed and slightly more cholesterol and phospholipid.
- LDL - Almost all triglycerides removed, high cholesterol and phospholipid
- HDL - high concentration of protein, smaller amounts of cholesterol and phospholipids
What is lipoprotein lipase’s function?
It degrades TG (and phospholipids) in the bloodstream being carried by chylomicrons.
What hormones are secreted by adipose tissue?
leptin and adiponectin
What are the 3 functions of the liver in lipid metabolism?
- Degrade fatty acids for energy use
- Synthesize triglycerides (mainly from carbs but also protein)
- Synthesize other lipids from fatty acids ie cholesterol and phospholipids
What are the three steps that the body uses to form ATP from triglycerides?
- Split (Hydrolyze) TG into fatty acids and glycerol. Glycerol enters the cytoplasm and into glycolosis to form pyruvate.
- Carrier mediated transportation - Fatty acids bind with carnitine to enter the mitochondria.
- Beta oxidation - progressive release of acetyl-CoA and hydrogen ions from fatty acids (with acetyl coA entering into Kreb’s cycle).
Name 3 ketone bodies and explain how we can generate ATP from ketones.
Acetoacetic Acid, beta hydroxybutyric acid, and acetone
After fatty acids are split into acetyl CoA, two molecules condense to form acetoacetic acid which is transported to tissues for energy. They diffuse into tissues where reverse reactions occur and acetyl CoA formed which enter the citric acid cycle.
What are the principle intermediates in converting acetyl CoA into fatty acids?
Malonyl-CoA and NADPH
What hormones regulate fat utilization?
Epinephrine
Insulin
Glucocorticoids
Thyroid Hormone
How does the body downregulate triglyceride metabolism in the presence of high carbs?
- High amounts of glycerol 3-phosphate (substrate of glycolysis) – binds triglycerides
- Faster fatty acid synthesis than fatty acid degradation
- Acetyl CoA carboxylase (enzyme in lipogenesis) upregulation – upregulation due to high levels intermediates of the citric acid cycle
What are 5 functions of phospholipids?
o Component of blood lipoproteins
o Component of thromboplastin (cephalins)
o Component of nerve sheath (sphingomyelin)
o Donors of phosphate radicals during different chemical processes
o Component of structural elements of cells (mainly membranes)
How is the concentration of cholesterol regulated?
o Daily cholesterol ingestion
o High dietary saturated fat content (especially when combined with obesity) (increases)
o Low dietary unsaturated fat content (decreases)
o Hypoinsulinaemia or hypothyroidism (increases)
o Genetic disorders (increases)
What are the 10 essential amino acids?
Bonus: what is the 11th for cats only?
Argue on a HILL, Met 3, tripped on a Valise of phennel
Arginine
Histadine
Isoleucine
Leucine
Lysine
Methionine
Threonine
Tryptophan
Valine
Phenylalanine
Bonus: Taurine
What are the functional roles of the major types of plasma proteins and where are they made?
Albumin - provides colloid oncotic pressure, made in liver
Globulin - Enzymatic functions and natural/acquired immunity (50-80% made in liver, rest by lymphoid tissue)
Fibrinogen - forms blood clots, made in liver
What are the two steps the body uses to form energy from protein?
- Deamination - the removal of amino groups from amino acids by transamination (transfer of amino group to some acceptor substance)
(ammonia released by deamination) - Oxidation of deaminated amino acids – Conversion of alpha-keto acid to substance that can enter the citric acid cycle, participate in carbohydrate-lipid metabolism (eg. acetyl CoA) or serve as an alternative energy source (eg. ketone bodies)
Where is urea synthesized?
The liver
What is obligatory protein loss?
25-30g/day of protein are degraded and oxidized each day (with the body preferentially using carbohydrates and fat sources as energy substrates unless multiple week starvation occurs)
Which hormones regulate protein metabolism and how?
- Growth hormone – Increases the synthesis of cellular proteins
- Insulin – Necessary for protein synthesis
- Glucocorticoids – Increases breakdown of most tissue proteins
- Testosterone and estrogen – Increases protein deposition in tissues (estrogen lesser extent)
- Thyroxine – Increases metabolism of cells & thus protein metabolism (if inadequate fat-carbohydrate available)
What is the functional unit of the liver and what are its components?
Liver lobule
Central vein
Cellular Plates
Bile Canaliculi
Portal venules
Sinusoids
Hepatic arterioles
Endothelial cells
Kupffer cells
Spaces of Disse
- Portal blood drains through central vein into hepatic veins and vena cava.
- Cellular plates radiate from central vein with bile canaliculi at center which line plates and transport bile to bile ducts.
- Portal venules provide blood from portal vein to sinusoids which transport blood from portal venules to central vein.
- Hepatic arterioles carry blood from systemic circulation to sinusoids
- S of D: Space b/w endothelium and hepatic cells that connect with lymphatic vessels to remove fluid
The liver has (high/low) blood flow and (high/low) vascular resistance.
High
Low
How does cirrhosis cause portal hypertension and what does that result in?
Cirrhosis increases resistance to blood flow and results in excessive fluid loss and increased capillary blood pressure causing ascites.
What cells release what factor to stimulate and terminate liver regeneration?
Stimulate - Hepatocyte growth factor by mesenchymal cells
Terminate - Transforming growth factor (TGF - B) by hepatocytes
What 3 major vitamins have large stores in the liver
Vitamin A
Vitamin D
Vitamin B12
List 3 substances formed in the liver that are used in the coagulation process.
Fibrinogen
Prothrombin
Factor VII (7)
What are the synonyms for Factor I, II, III, and IV? Which of the coagulation factors are vitamin K dependent?
Vitamin K dependent –> 2, 7, 9, 10
Hemolytic anemia results in high (conjugated/unconjugated) bilirubin while biliary obstructions results in high (conjugated/unconjugated) bilirubin?
Unconjugated (RBC rupture releasing hemoglobin which splits into components eventually creating pyrrole which forms biliverdin which is reduced to free bilirubin)
Conjugated (since bile canniculi rupture and bile leaks into vessels)
What portion of the brain is responsible for hunger and satiety?
Where is each center located?
Hypothalamus
Feeding center - lateral nuclei
Satiety Center - ventromedial nuclei
What part of the brain controls the mechanical process of eating
The brainstem, amygdala, and prefrontal cortex
What are three functions of Pro-opiomelanocortin (POMC) & cocaine & amphetamine-related transcript (CART) neurons?
What hormones stimulate these neurons?
DECREASE food intake
INCREASE energy expenditure
PRODUCE alpha-MSH
Hormones: insulin, leptin, CCK
What are three functions of Neuropeptide Y (NPY) & Agouti-related protein (AGRP)?
They are stimulated by which hormone(s)?
INCREASE food intake
DECREASE energy expenditure
Hormone: ghrelin
Are the following hormones anorexigenic or orexigenic?
- Serotonin
- Melanin concentrating hormone
- Norepinephrine
- Endorphins
- Galanin
- Cholecystokinin
- AA – glutamate and gamma aminobutyric acid
- Glucagon like peptide
- Cortisol
- Peptide YY
- ano
- o
- ano
- o
- o
- ano
- o
- ano
- o
- ano
Where is ghrelin produced?
Oxyntic cells of the stomach
What are 5 effects of leptin?
o DEACTIVATES appetite stimulator neurons (NPY & AGRP)
o ACTIVATES appetite suppressor neurons (POMC)
o INCREASES production of corticotropin-releasing hormone
o INCREASES sympathetic nervous system activity which increases metabolic rate and energy expenditure
o DECREASES insulin secretion which decreases energy storage.
What are the synonyms for B vitamins 2, 3, 9, 12?
Thiamine
Riboflavin
Niacin
Folic acid
Cobalamin
What signs would be seen with a thiamine deficiency?
Neuro, cardiac, GI
What does vitamin A deficiency cause?
Night blindness and abnormal epithelial growth
What does a deficiency in folic acid cause?
Macrocytic anemia (similar to pernicious anemia) and can be treated with folic acid alone.
Pernicious anemia and demyelination are caused by a lack of what vitamin?
B12
In which part of the GI does Vitamin D help increase absorption of Ca?
ileum
What does a deficiency in vitamin C cause? (not scurvy)
Weakens collagen fibers throughout the body
Low/high magnesium can cause cardiac arrhythmias?
Low
High can cause neuro depression
carbonic anhydrase, lactic dehydrogenase & peptidases require which mineral to function?
Zinc
During rest there are (low/high) levels of ADP and energy metabolism will be slow. During activity there are (low/high) levels of ADP and energy metabolism will accelerate
Low
High
Explain non-shivering thermogenesis
Stimulation of the sympathetic nervous system where epinephrine and norepinephrine increase metabolic activity and heat generation.
Particularly effective with brown fat where sympathetic stimulation uncouples oxidative phosphorylation resulting in heat as opposed to ATP
What is the percent breakdown of how heat is lost from the skin surface?
- Radiation (60%) – causes heat loss in the form of infrared rays radiated from the body
- Conduction (3%) – heat loss that occurs by direct contact with an object
- Convection (15%) – heat loss that results from air movement carrying conducted heat away from the body
- Evaporation (22%) – can be insensible & results in continual heat loss through the skin, lungs and sweating
Which cytokine is most involved in fever production?
IL-1
What does a kinase do?
Phosphorylate
What are the 3 general classes of hormones?
- polypeptides and proteins secreted for pancreas (insulin/glucagon), anterior and posterior pituitary, parathyroid etc
- steroids secreted from adrenal cortex (aldosterone and cortisol), ovaries, testes
- derivatives of the amino acid tyrosine secreted by thryroid and adrenal medullae (epi/norepi)
What receptors are located on the cell membrane? Cytoplasm? Nucleus?
- Polypeptides, proteins, catacholemines
- steroids
- thryoid hormone
Where are amine hormones derived from?
Thyroid gland and adrenal medulla
What is the first step to a hormone affecting a target tissue?
Formation of a hormone-receptor complex
Describe the mechanism of action of a G protein receptor.
When the hormone binds to the extracellular part of the receptor, conformational changes occur in the receptor that activate the G proteins & induces intracellular signals
Signals either (1) open or close cell membrane ion channels, (2) change the activity of an enzyme in the cytoplasm of the cell, or (3) activate gene transcription
How does an enzyme linked hormone receptor work?
-
o Have their hormone-binding site on the outside of the cell wall & their catalytic or enzyme-binding site on the inside
o When hormone binds to outside, an enzyme immediately inside the cell is activated
What is a hormone response element?
Activated hormone-receptor complex that binds with a specific promoter sequence of the DNA; either activates or represses transcription of specific genes & formation of messenger RNA & protein synthesis
Examples of proteins that use cAMP as second messenger
ACTH, AngII, calcitonin, glucagon, GHRH, PTH, secretin, somatostatic, TSH
What is the mechanism of action of the second messenger phospholipase C?
- This enzyme catalyzes the breakdown of some phospholipids in the cell membrane (PIP2) into 2 different second messenger products (IP3 & DAG)
o IP3 (inositol triphosphate) – mobilizes Ca2+ from mitochondria & ER; Ca2+ has 2nd messenger effect
o DAG – activates protein kinase C which phosphorylates large number of proteins leading to cell’s response; lipid portion of DAG = arachidonic acid
What is the mechanism of action of the calcium-calmondulin second messenger system?
- operates in response to entry of Ca2+ into the cells
- Upon entering the cell, Ca2+ ions bind with the protein calmodulin (4 Ca2+ sites)
o Once sites are bound with Ca2+, calmodulin changes shape & initiates multiple effects inside the cell including activation or inhibition of protein kinases
Steroid hormones increase/decrease protein synthesis.
Increase
Thyroid hormone increases/decreases gene transcription in the cell nucleus?
Increases
What is an alternative name for ADH and what does it control?
Vasopression, rate of excretion of water into the urine.
What does somatostatin do?
Inhibit GH release
What are three metabolic effects of growth hormone?
Increased protein synthesis, decreased glucose utilization (conserve carbs), decrease fat stores (act as protein sparer)3
Under the influence of GH, what is used preferentially for energy?
Fat (instead of carbs or protein)
What is the ketogenic effect of excessive growth hormone?
o Can produce large quantities of acetoacetic acid from the liver & is released into body (ketosis)
o Excessive mobilization of fat from fat tissue frequently causes fatty liver
GH increases/decreases insulin resistance?
Increases
What is an alterate name for insulin like growth factor?
IGF-1?
Somatomedin
Somatomedin C
IGF has a faster/slower duration of action than GH?
Slower
What are some inhibitors of GH?
↑BG, ↑FFAs, aging, obesity, GHIH (somatostatin), GH (exogenous), somatomedins
What are some stimulators of GH?
↓BG, ↓FFAs, ↑blood amino acids, starvation/fasting, protein deficiency, trauma, stress, excitement, exercise, testosterone/estrogen, deep sleep, GHRH, ghrelin
o Signals depicting emotion, stress, trauma = epi, norepi, dopamine, & serotonin
How does GHRH control GH secretion?
- GHRH attaches to specific cell membrane receptors on outer surfaces of the GH cell in the pituitary gland
o Receptors activate adenylyl cyclase system ↑intracellular cAMP ↑Ca2+ transport into the cell GH secretory vesicles fuse with cell membrane & release hormone into blood
What are two important hormones produced by the posterior pituitary gland? Where are they specifically formed?
ADH (supraoptic nuclei) and oxytocin (paraventricular nuclei)
What are neurophysins?
Carrier proteins for hormones in the posterior pituitary
Presence of ADH causes collecting ducts to be permeable/impermeable to water and causes concentrated/dilute urine
permeable
concentrated
What are three stimulators of ADH secretion?
Increased ECF osmolality
Low blood volume
Low blood pressure
Which gland secretes calcitonin?
Thyroid gland
T3 is more/less potent than T4 and exists in tissues longer/shorter than T4?
More potent (x 4)
shorter
