Week 2 Flashcards
2 monosaccharides that make up sucrose?
Glucose and Fructose
2 monosaccharides that make up lactose?
Galactose and glucose
2 monosaccharides that make up maltose?
2 glucoses
Oligosaccharides?
3-10 monosaccharides
Polysaccharide?
More than 10 monosaccharides
Mostly storage
Linear and branched
What is starch made of and how is it linked?
Glucose
With alpha 1-4 glycosidic bonds
What catabolizes starch?
Amylase
What is glycogen made of and how is it linked?
Glucose
Linear links are alpha 1-4
Branches are alpha 1-6
Where is glycogen stored in humans and animals?
Liver and muscles
What is inulin?
Polymer of fructose
Found in onions and garlic
Water soluble
Not absorbed into blood and not secreted
Inulin is used for?
Determining glomerular filtration rate ie kidney function
Injected into bloodstream
What glycosaminoglycans ie GAGs?
Repeating disaccharide units with acidic sugar(COOH) and an amino Acetyl sugar.
GAGs are found where and one of their functions?
Cell surface or ECM
Long chains found in mucous and fluids around joints
Important structural components
Negatively charged and attract water to provide cushioning for structures
What bond can amylase not digest?
Alpha 1-6 glycosidic bonds
What is a source of glucose during hypoglycemia?
Liver glycogen
Major components of ECM?
Collagen and elastin
Another name for GAGs?
Mucopolysaccharides
List 6 major types of Mucopolysaccharides aka GAGs (glycosaminoglycans)?
Chondroitin Sulfate Hyaluronic Acid Heparin Sulfate Heparin Dermatan sulfate Keratan sulfate
Location of chondroitin sulfate?
Cartilage, bone, aorta, ligaments
Location of hyaluronic acid?
ECM, synovial fluid and vitreous humor
Location of heparan sulfate?
Basement membrane
Location of heparin?
Mast cell granules and anticoagulant
Location of dermatan sulfate?
Skin, blood vessels, and heart valves
Keratin sulfate location?
Cornea, cartilage, bone
2 GAGs involved with Hurler Syndrome?
Heparin and Dermatan sulfate
2 GAGs involved with Hunter Syndrome?
Heparan sulfate and Dermatan sulfate
What are proteoglycans?
Structural polysaccharides located in ECM
They are GAG tails attached to a protein core that is rich in serine and threonine
Each Proteoglycan then attaches to hyaluronan molecule via linker protein
Proteoglycan plus collagen = Cartilage
Cellulose?
Glucose monomers in long chains link by beta 1-4 glycosidic bonds
Found in plants and can’t be digested by humans although they do provide fiber which is useful in our digestion to keep things moving
What is chitin?
Structural poly saccharide found in exoskeletons of Arthropoda and fungal cell walls
4 steps in starch digestion?
Where and what?
- Mouth- Salivary amylase hydrolyzes alpha 1-4 bonds
- Stomach- high acid inactivates amylase and stops carb digestion temporarily
- Duodenum aka top of small intestine pancreatic alpha amylase continues breaking alpha 1-4 bonds
- Upper jenjunum mucosal lining processes the breaking of alpha 1-6 branch link
Lactose digestion?
Remember beta 1-4 linkage of galactose and glucose
Lactase in small intestine
If a person is lactase deficient what happens? Or what happens if any disaccharide reaches large intestine and colon?
They draw water in to intestine colon.
Bacteria break lactose down/ferment it in large intestine producing H2, lactic acid, CO2 and two carbon metabolites like acetic acid.
Gas and diarrhea
What are glucans and fructans?
Polysaccharides made by bacteria using glusosyltransferase or fructosyltransferase
Glucan makes up 10-20% of plaque
What is dextran?
Branched glucan that modulates bacterial adhesion
Aka
Glucans glue other bacteria’s like s mutans to teeth!!!!
What is an important bacterial made polysaccharide other that glucans or dextrans?
Levan
How is levan catalyze/made?
And what does it do?
Made by reaction with levansucrase.
Makes plaque by contributing to ecpm aka extracellular polysaccharide matrix
3 examples of complex carbs and what are complex carbs?
Sugars with proteins, lipids, enzymes with diverse functions
- Glycoproteins
- Saliva
- Glycolipids
Alternate name for glycolysis?
Embden-Meyerhof Pathway
Alternate names for citric acid cycle?
Krebs Cycle
TCA (tricarboxylic acid) cycle
Alternate name for Pentose Phosphate Pathway?
Hexose monophosphate shunt
Alternate name for Cori Cycle?
Lactic Acid Cycle
Alternate name for electron transport chain ie ETC?
Respiratory Chain
Livers role in glycogen storage?
Maintains steady blood glucose levels
Glucose is stored in liver during fed state and released from liver between meals
High insulin stimulates storage as glycogen and suppresses glucagon
Insulin also stimulate glucose uptake into muscles, fat cell and kidney etc
Glucagon stimulates breakdown of liver glycogen
Low blood sugar stimulates what to be released from pancreas?
Glucagon which stimulates glycogenolysis in liver
Breakdown of glycogen to glucose to be released in blood
What happens when liver runs out of glycogen to use for glycogenolysis and blood sugar is still low?
Body’s saves sugars for brain and RBCs and makes ketones from lipids via ketogenesis
What stimulates ketogenesis to begin?
Low levels of insulin and glucose
Starving state
What are ketones?
Alternative fuel made from lipids used by muscles and body organs
What is the pancreas’s roll in maintaining blood sugar?
Releases either insulin or glucagon depending on level of glucose in blood
Type one diabetes 5 major characteristics- Age onset Nourishment state at onset Genetic predisposition Defect or deficiency Treatment
- Rapid childhood or puberty
- Often undernourished
- Moderate
- Beta cells destroyed no insulin production
- Always treated with insulin
Type two diabetes 5 major characteristics-
- Age onset
- Nourishment state at onset
- Genetic predisposition
- Defect or deficiency
- Treatment
- After 35, gradually develops
- Usually obese
- Strong genetic link
- Resistant to insulin and beta cells can’t produce enough insulin
- Lifestyle, potentially insulin and other hypoglycemic drugs and blood pressure control
What are beta cells?
Cells in pancreas islets of Langerhans that produce and release insulin
What is GLUT1 function, Km and location?
Basal uptake of glucose
1mM Km aka high affinity
Found in plasma membrane of most cells
Maintains basal or continuous base rate of glucose uptake for cells
GLUT2 transporters function, Km and location?
Found in the liver and pancreatic tissues
Liver they take up and release glucose
Pancreas they function as the beta cells glucose sensor
Km is 15 aka low affinity meaning glucose needs to be high for these to function
GLUT3 transporter location Km and function?
Found in most tissues
1Km = high affinity
Maintains basal rate of uptake and transports glucose in neuronal tissues including brain
GLUT4 transporter location, Km and function?
Skeletal muscles and adipose tissue
5 Km = medium affinity
Insulin stimulated glucose uptake in skeletal muscle and cardiac muscle to store glucose in muscles
Adipose tissues uptake and convert glucose to triglycerides for storage
What are pancreatic alpha cells?
They produce glucagon and are located in the islets of langerhans
How are glucagon and insulin balanced?
The release of insulin from pancreatic beta cells inhibits glucagon release from alpha cells and the pancreas regulates both of them which are released from islets to maintain balance of glucose in blood from either liver and or food intake and needs of the body for glucose
Describe the process of a Pancreatic beta cell exposed to blood glucose from carb rich foods?
- GLUT2 transporter (only active in high glucose aka high Km and low affinity) takes up glucose
- Glucose phosphorylated to glu-6-phosphate by Hexokinase IV aka glucokinase
- G6P goes into glycolysis and ETC to make ATP
- ATP used trigger signal pathway to make insulin which is secreted to blood
- Insulin in blood triggers uptake of glucose by muscles and adipose tissues to store it.
What happens when there is a mutation of Hexokinase IV/Glucokinase?
First step in glycolysis in pancreatic beta cells doesn’t happen and-
It doesn’t transfer the signal that glucose is high thus less insulin is made resulting in hypoglycemia…. Happens in Type II diabetes
2 things that normally happen when there is high sugar/carbs?
GLUT2 transporters in both liver and pancreas start to work to uptake glucose.
- Liver stores glucose as glycogen
- Pancreas releases insulin to signal muscles and fat to uptake and store glucose
What happens to monosaccharide sugars in the small intestine/jejunum?
Taken up by transporters
GLUT5- Fructose
SGLT1- Glactose and Glucose
All are the sent to circulation via GLUT2 transporter
What happens to disaccharide sugars in the small intestine/jejunum?
Alpha 1-6 bonds broken down to monosaccharides by brush border disaccharidases.
In what parts of the body is aerobic glucose metabolism important?
Heart, brain, skeletal muscle fibers
Where may glycolysis occur anaerobically?
Erythrocytes and exercising skeletal muscle
Where does glycolysis happen?
In cytosol
3 main fates of pyruvate after glycolysis and 2 minor ones?
Major-
- Most normal Aerobic- Acetyl CoA to Krebs/TCA
- Anaerobic aka exercise when O2 is low in muscles- to Lactate
- in low glucose/fasting state to Oxaloacetate to gluconeogenesis to make glucose for brain
Minor-
- To alanine by transamination to use up excess nitrogen
- To ethanol via fermentation In microorganisms koi
What happens to lactate when it is made in anaerobic exercise conditions?
When NADH is high in muscles, pyr to lac favored
Lactate builds up in muscle causing intercellular pH to drop
Lactate diffuses into blood and goes to liver to make pyruvate and into gluconeogensis
What does pyruvate dehydrogenase complex do and what is it?
Makes pyruvate into Acetyl CoA so it can enter the Citric Acid Cycle or used to make fatty acids, steroids or ketone bodies (lipid metabolism)
It is irreversible
What are cofactors needed for pyruvate dehydrogenase?
Thiamine pyrophosphate Coenzyme A Lipoate (form of Lipoic Acid) FAD NAD+
What happens in arsenic poisoning?
Arsenite binds to lipoic acid and inhibits PDH from making Acetyl CoA
What is another name for thiamine?
Vitamin B1
What is a disease caused by low thiamine?
Beriberi
Which leads Wernicke-Korsakoff syndrome in severe cases
Thiamine needed by PDH complex to convert pyruvate to Acetyl CoA not made
Symptoms of Beriberi
Abnormalities in peripheral nervous system like numbness or reflexes
Painful weak muscles
Enlarged heart
Wernicke-Korsakoff syndrome symptoms?
Apathy
Loss of memory
Rhythmical back and forth with eyes
Confusion->coma-> death
Where do carbs, amino acids and fatty acids converge?
Citric Acid Cycle
What is the main function of the citric acid cycle?
To provide intermediates (GTP, FADH2, NADH)needed for ETC and ATP production
What is a secondary function or the citric acid cycle/krebs?
Provide intermediates for for other reactions such as making amino acids
Krebs cycle score card?
1 glucose = 2 pyruvate = 2 turns of the cycle = 2 GTP, 2 FADH2, 6 NADH
Those are fed into ETC to make a total of 24 ATP
Where does the Citric Acid Cycle take place?
In the mitochondrial matrix
Remember small molecule diffuse across pore in the outer membrane
Inner membrane is tight and has transporters
4 intermediates in TCA cycle page she pointed out and what the do?
Citrate- shuttles Acetyl CoA to cytoplasm for fatty acid synthesis
Succinyl-CoA - used for heme synthesis and activating ketone bodies
Malate- Malate shuttle used to transfer oxaloacetate out of mitochondria during gluconeogenensis
Alpha-ketoglutarate- used for AA synth
What is final product of TCA?
Oxaloacetate
What is the pentose phosphate pathway and it’s purpose?
Uses glucose and run parallel. Makes NADPH (irreversible) and a 5 carbon sugar ribose for nucleotide synthesis (irreversible)
Where does the pentose phosphate pathway take place?
Cytosol
The irreversible pentose phosphate pathway?
Oxidative
Uses glucose-6-phosphate to make NADPH for use in fatty acid synth, glutathione reduction and detoxification reactions
The reversible pentose phosphate pathway?
Non-oxidative
Uses fructose 6 phosphate or glyceraldehyde 3 phosphate to make ribose for nucleotides
Tissues where the pentose phosphate pathway is active?
Liver, adipose, adrenal cortex, thyroid, mammary glands and erythrocytes
Tissues where the ppp is not very active?
Muscle and brain where almost all glucose is used in glycolysis
What is the only source of glutathione in red blood cells and what does it do?
G6PD via the irreversible oxidative PPP pathway
Glutathione eliminates free radicals in RBCs
What is G6PD deficiency and what are the symptoms?
Genetic disorder occurring mostly in males RBCs break down prematurely leading to: Hemolysis Hemolytic anemia Jaundice
What is the Entner-Doudorof Pathway?
Alternative to glycolysis used by bacteria
Gluconeogenesis?
Uses lactate/lactate dehydrogenase or Alanine/ALT (alanine aminotransferase) to make pyruvate to make oxaloacetate to do reverse glycolysis and make glucose for brain in times of low glucose and starvation/fasting state
Also uses glycerol
Where does gluconeogenesis happen?
In the liver
Starts in mitochondria where pyruvate is converted to oxaloacetate
Cori Cycle composition and purposes?
Lactic Acid cycle
Uses lactic acid to connect glycolysis and gluconeogenesis
Rapid source of ATP in muscles during high activity
Prevent lactic acidosis by moving lactate out of muscle into liver
Summarize Cori Cycle reactions?
In muscles:
Glucose-> glycolysis makes 2 ATP
Ends up with 2 pyruvate
Low O2 = no terminal receptor for ETC so makes 2 Lactate
Which diffuse into blood and go to liver
2 Lactate-> 2 pyruvate-> uses 6 ATP to make glucose release back into blood to go back to muscles
Not very efficient!
Glycogenesis and glycogenolysis?
Stores glucose as glycogen and breaks the glycogen down
All happens in liver and muscle
Storage enzyme Glycogen Synthase activated by insulin
Breakdown enzyme phosphorylase inhibit by insulin
Glycogenolysis helps with what?
Immediate energy in muscles during exercise when not enough Glucose and O2 can be delivered by blood
Liver glycogen provides energy during hypoglycemia
Sources of glucose?
Food to blood stream
Glycogen storage in liver and muscles
Gluconeogenesis in liver
Another names for ETC and purpose of it?
Oxidative phosphorylation
Make ATP
Creates a proton gradient uses O2 as final electron acceptor to make ATP
Name 3 inhibitor/uncouplers of ETC/oxidative phosphorylation?
Cyanide- binds irreversibly to cytochrome
CO- binds to cytochrome and hemoglobin and myoglobin less O2 for ETC
Aspirin/ 2-4 dinitrophenol- decreases proton gradient
What happens in ETC oxidative phosphorylation uncoupling?
ATP synth disrupted,
In hypoxia glycolysis increase to meet ATP needs, since no O2 glycolysis makes lactate leading to lactic acidosis
Nerves and cardiac muscles can’t meet ATP needs this way
Disaster! Membrane potential collapses, enzymes leak, lactic acidosis, protein precipitation and coagulation necrosis = myocardial infarction
Von Gierke disease GSD type?
GSD 1
Von Gierke enzymes affected?
1a is glucose 6 phosphatase
1b is glucose 6 phosphate translocase
Both affect glycogen breakdown and lead to low blood sugar
Affects liver and kidneys
Pompe disease GSD type?
Type II
Pompe Disease enzymes affected?
Alpha-glucosidase
Breaks alpha 1-4 glycogen bonds
Leads to build up of glycogen in tissues
Liver heart skeletal muscle lysosomes
Cori disease GSD type?
GSD Type III
Cori Disease enzyme affected?
Mutation in AGL gene which codes for Glycogen Debranching Enzyme for the 1-6 bonds
Causes buildup of glycogen in liver and muscles
Andersen GSD type?
GSD Type IV
Andersen affected enzyme?
Deficiency in glycogen debranching enzyme
Causes glycogen to build up and impairs function of some organs especially the liver and muscles
McArdle disorder GSD type?
Type V
McArdle disease affected enzyme?
Muscle glycogen phosphorylase ie myophosphorylase
Affects breakdown of glycogen in muscles
Hers disease GSD type?
GSD type VI
Hers disease enzyme affected?
Hepatic glycogen phosphorylase
Can’t break down liver glycogen
Name 2 mucopolysaccharide diseases?
Hunter and Hurler syndromes
Hunter versus Hurler severity?
Hunter less severe but more aggressive
Hunter type and affected GAGs?
Mucopolysacchardosis Type II
Affects heparan sulfate and Dermatan sulfate
Hunter clinical features?
Affects young males Macrocephaly Thick lips and gingiva Broad nose and flared nostrils Protruding tongue Abnormal bone skin size No corneal clouding
Hunter inheritance pattern?
X-linked recessive
Hurler inheritance pattern?
Autosomal recessive
Hurler type and affected GAGs?
Mucopolysaccharidosis type I
Affected GAGs heparin sulfate and Dermatan sulfate
Hurler clinical features?
Development delay, cognitive impairment, enlarge tissues and organs from GAGs accumulation in lysosomes, macrocephaly, macroglossia, enlarge liver and spleen, corneal clouding, thicken gingival and flat nasal bridge, flared and upturned nose
Large mouth and lips
Pitted hypoplastic primary teach
Narrow dentinal tubules
Micro gaps in enamel dentin junction
Cyst like lesions that destroy bone of unerrupted permanent teeth
4 Lipid functions?
Cellular structure
Metabolism
Transport of nutrients
Energy storage
3 types of lipids?
Triglycerides aka fat
Phospholipids
Steroids
Components of triglyceride?
Glycerol backbone with 3 fatty acid tails
3 types of lipids in membranes?
Phospholipids, glycolipids, sterols
4 Types of phospholipids and where they are found?
Phosphatidycholine- membrane
Spingomyelin- membrane and nerve tissue
Lecithin-membrane
Cephalins- nerve tissue
Glycolipid function?
Membrane stability
Sterol functions?
Precursor for steroids bile salts sex hormones and vit D
Also membrane fluidity/stability regulation
Differences between trans and cis unsaturated fats and saturated?
Saturated is solid at room temperature
Cis unsaturated has more double bonds and bent tails, liquid at room temp lower LDL and increase HDL
Trans not natural and solid at room temp
Name two essential fatty acids?
Linolenic acid
Linoleic acid
Essential fatty acid function and what a deficit can lead to?
Structural component of cell membrane
Deficiency leads to scaly dermatitis- inability to provide water barrier in skin and loss of water
Linolenic Acid?
Precursor to omega 3
FroM salmon
Reduces TAGs aka triglycerides, prevents blood clots by lowering thromboxane
Linoleic Acid?
Precursor to Omega 6
Found in nuts and seeds
Lowers HDL and LDL
2 conditionally essential fatty acids?
Oleic acid
Arachidonic Acids
Oleic Acid?
Body makes a small amount so must get from food
Arachidonic Acid?
Precursors to prostaglandin synthesis and eicosanoids
Only needed if there is deficiency in linoleic acid or lack of conversion from linoleic to arachidonic
What starts fatty acid synthesis and why?
Citrate transported from mitochondria to cytoplasm via citrate shuttle
In high energy/ATP state step TCA cycle not needed to make products for ETC and Isocitrate dehydrogenase inhibited. This is rate limiting step and slows/stops TCA causing citrate to leave for FA synthesis
2 step in fatty acid synthesis?
Citrate is turned into Acetyl CoA and Oxaloacetate by ATP Citrate Lyase
3rd step in Fatty Acid synthesis?
Acetyl group plus Malonyl group make Palmitate the most common FA
This is what happens to excess carbs in fed state, they get stored as fat
Triglyceride functions?
Energy source
Stores in adipose tissues
Transported in plasma by lipoproteins
Increase in them is linked to atherosclerosis, heart disease and stroke
How are eicosanoids derived?
In response to hormones or cell damage- Phospholipase A2 releases arachidonic acid from plasma membrane phospholipids
What is a major eicosanoid production pathway and what does is make?
COX (cyclooxygenase) pathway
Makes prostaglandins prostacyclin and thrombaxanes
Prostaglandins are involved in what and what inhibits the pathway to make them?
Vasodilation, inflammatory pain
NSAIDs (aspirin, Advil, naproxen) inhibit Cox pathways blocking their formation
Where are bile salts formed?
From cholesterol in liver
What do bile salts do?
Aid in lipid absorption by emulsifying fats
What happens to bile salts?
Reabsorbed in ileum and returned to liver
Extra is stored in gall bladder
What happens to bile salts in CF patients?
Thickening of mucous barrier in intestine blocks bile salt reassorbtion and causes bile salt loss in feces
What else go wrong in CF patients other than bile salts being excreted regarding Lipid metabolism?
Pancreatic ducts get clogged and enzymes can’t reach intestine.
Only digest fats with lingual and gastric lipases
5 classifications of Lipoproteins?
Chylomicron Bad ones- VLDL-Very low density lipoprotein IDL- intermediate density lipoprotein LDL- low density lipoprotein Good one HDL- high density lipoprotein
Steps in fat digestion?
- Triglycerides and cholesterol broken down to free cholesterol and free FAs and monoglycerides
- All those are solubilized by bile salts and transported to microvilli and absorbed
- Reassembled into triglycerides and cholesterol which then are made into chylomicrons
What happens to chylomicron after it is made by intestine mucosa?
- Chylomicrons are secreted to lymph and blood systems
They have apo CII on their surface
2 When they reach tissues like adipose and muscles the Apo CII activates Lipoprotein lipase to break them down
3 Chylomicron remnants get sent to the liver and Te ie Ed by the remnant receptor
What happens in case of Lipoprotein Lipase or Apo CII deficiency?
Chylomicrons accumulate in plasma triglycerides not degraded and increase risk of acute pancreatitis aka inflammation of the pancreas and abdominal pain
How are VLDLs made and what do they do?
Made in liver from chylomicrons remnants or synthesized
Carry endogenous triglycerides to peripheral tissues
Do VLDLs have Apo CII on surface?
Yes when they mature from nascent VLDL into mature one they pick up Apo CII, Apo E and cholesteryl
What happens to VLDLs when they reach tissues?
Apo CII activates LPL (lipoprotein lipase) which releases fatty acids, Apos and phospholipids which can make HDL
Remnant is IDL
Some IDL get picked up by ApoE receptor in liver
Some IDL stays in blood and get broken down to LDL
What happens when there is and imbalance in liver triglycerides synthesis and VLDL synthesis?
Non alcoholic fatty liver
Nonalcoholic fatty liver often happens in what two diseases?
Obesity and type II diabetes
How are LDLs made and what do they do?
Made from remnants of VLDLs and IDLs
They are cholesterol rich and deliver cholesterol to tissues
What happens to LDLs?
1/2 cleared by liver picked up by hepatic LDL receptors and the rest are picked up by scavenger LDL receptors in blood and plasma systems
What happens when cholesterol is high?
Scavenger receptors are NOT down regulated and they pick up cholesterol esters and lead to plaque formation in arteries
2 things HDL does?
- Transports cholesterol from peripheral tissues to other cell, other lipoproteins, or to liver to clear
- Is a circulating reservoir for apo lipoproteins
How is cholesterol made?
Acetyl CoA from beta oxidation make HMG CoA
HMG CoA reductase which is activated by insulin and inhibited by glucagon and statins converts HMG CoA to Mevalonate which then goes through a few more steps to make cholesterol
Where is cholesterol made?
All tissues but mainly liver, intestine and reproductive tissues
What happens when sterol levels are low?
Transcript factor up-regulates HMG CoA reductase synthesis so more cholesterol can be made
How are triglycerides broken down in adipose tissue?
By lipase into glycerol and FAs
Glycerol sent to liver
FAs transported out of adipose tissue to tissues where needed where beta oxidation happens to make Acetyl CoA
What enzymes breaks down glycerol in liver and what does it turn into?
Glycerol kinase makes glycerol 3 phosphate which then is transformed to Glucose 6 Phosphate by plugging it into gluconeogenesis
Another name for beta oxidation?
Fatty Acid Spiral
What does beta oxidation do and when is it active?
Makes Acetyl CoA froM FAs to plug into the Citric Acid Cycle to make energy
It is active in low energy times
Insulin stimulates fatty acid synthesis and storage
How does beta oxidation work?
Free FAs taken up by cells that need energy
They are transformed to Acyl CoA which is transported into mitochondria via the Carnitine shuttle as Acylcarnitine then separated and oxidized to Acetyl CoA
What does the presence of Acetyl CoA from beta oxidation stimulate?
It activates pyruvate dehydrogenase which stimulates gluconeogenesis
3 potential fates of Acetyl CoA?
- TCA cycle and ATP energy
- HMG CoA which can take two different pathways ketone bodies or cholesterol
- Fatty Acid Synthesis and storage via malonyl CoA
2 fates of HMG CoA?
Cholesterol synthesis via HMG CoA lyase
Or Ketone body synthesis with HMG reductase
What conditions trigger ketone body synthesis and what tissues can use them?
Fasting/starving state or diabetes mellitus
Liver makes them from Acetyl CoA
Skeletal and cardiac muscle use them first
After ~3 wks brain will metabolize them and muscles will stop using them as much (small molecules so they can cross blood brain barrier)
3 types of ketone bodies?
Acetoacetate
Can make
Acetone (spontaneous and dead end)or
3-hydroxybutyrate
Acetoacetate and 3-Hydroxybutyrate ketone body fates?
Transported by blood to tissues and converted back to Acetyl CoA and used inTCA cycle
What is spared during ketogenesis and how?
Protein
Pyruvate dehydrogenase blocked
Also no glucose uptake in brain
Ketoacidosis causes?
Low insulin high glucagon and epinephrine
FAs released from adipose tissues and excessive ketone synthesis
Also can be caused by infection or trauma from increased epi
Signs and symptoms of ketoacidosis?
Osmotic dieresis leads to dehydration’s and electrolyte imbalances = excessive thirst and frequent urination
Plasma pH level less than 7.3
Fruity odor on breath due to acetone production
Death
Why can’t liver use ketones for energy?
No thiophorase to convert ketone bodies to Acetyl CoA
Probably to prevent a useles cycle of liver making and using ketones
Name 5 lipid metabolic diseases?
Gauchers Niemann-pick Tay-Sachs Fabry’s Krabbe’s
