Carbohydrates, Lipids, Terminal Respiration, Nitrogen Flashcards
What is the function of the citric acid cycle?
- Common metabolic pathway for all food molecules (carbohydrates, fatty acids and amino acids)
- Produces large amounts of ATP
- Removes electrons from intermediate molecules and passes on to form NADH and FADH2.
What is the products of the citric acid cycle?
Large amounts of ATP, 4CO2 and 4H2O, NADH and FADH2
What molecule is central to the citric acid cycle?
Acetyl CoA
What molecules are found at the start and end of the citric acid cycle?
Citrate (C6) to oxaloacetate (C4)
Where does the citric acid cycle occur?
In the mitochondrial matrix.
Some NADH is in the cytoplasm from glycolysis and needs to be in the mitochondrial matrix. What resolves this issue?
The glycerol-phosphate shuttle, G-3-P
Where does NADH and FADH2 enter the terminal respiration chain?
NADH = first subunit FADH2 = Second sub-unit
How many enzymes are found in the terminal respiration chain?
4 enzyme sub-units
Where is the ubiquinone (Q) carrier located?
Between enzyme II and III.
What is the name of the molecule that transports electrons between complexes III and IV of the electron transport chain?
Cytochrome C
ATPase utilises which mechanism in order to generate ATP?
Binding-change mechanism
Describe how the ATP synthase functions.
Molecular turbine harness energy in the proton gradient (created from the proton motive force) which flow back down gradient into matrix. The energy is stored and the gradient is used to convert ADP and Pi to ATP.
What sub-unit of the ATP synthase does ADP and Pi enter?
Beta subunit
What are the names of the two parts of the ATP synthase?
F0 in membrane
F1 in matrix (catalyst, produces ATP)
What is the function of the ATP synthase?
Pumps in H+ ions into the matrix to form ATP.
What is the function of O2 in terminal respiration?
Acts as the final electron acceptor at enzyme IV to be re-oxidised to H2O.
Monomers of carbohydrates are linked together by what type of bonds?
Glycosidic
Catabolism of 1 mol of glucose to lactate generates how many net moles of ATP?
2 moles
Ingesting alcohol reduces which intermediate, particularly in the liver?
NAD+
What vitamin is not derived from a lipid?
Vitamin C
What vitamins are derived from lipids?
Vitamin A, D, E and K
Excess acetyl CoA from fatty acids gives rise to the formation of what?
Ketones
Which amino acid is central to nitrogen entering the body?
Glutamate
Which cycle is important in nitrogen metabolism?
Glucose-Alanine cycle
What are the main nitrogen containing molecules of the body.
Proteins, nucleic acids and nucleotides, biologically active amines and ahem-containing molecules.
What is the fate of dietary proteins?
Digested to AAs and then used in anabolic pathways
What happens to excess dietary proteins?
Proteins surplus to requirements are catabolised.
Describe the process of protein catabolism.
Amino acids converted to NH4+ of carbon skeletons.
- NH4+ enter urea cycle and produce urea (nitrogen excretion product)
- Carbon skeletons - form alpha-veto acid and enter citric acid cycle to produce glucose for gluconeogenesis, CO2, H2O and ATP.
How is the urea cycle linked with citric acid cycle?
Aspartate-arginine shunt
What are the sources of a steady state of amino acids?
- Digestion of dietary proteins in intestine
2. Degradation of intracellular proteins
How are dietary proteins digested?
- Enzymatically hydrolysed by peptidases in stomach.
- Trypsin and chymotrypsin (release by pancreas to SI) cut proteins into small peptides
- Aminopeptidase and carboxypeptidases A and B degrade peptides to AAs in small intestine.
What is the function of proteases?
Recognise sequence and cleave, produced in Zymogen form until activated.
Describe the role of glutamate in the transfer of nitrogen.
Only AA that can obtain nitrogen directly from NH4 and the only one that can give up nitrogen directly.
What would happen if glutamate did not exist?
Can’t convert N2 to AAs.
What enzyme is involved in the transamination process?
Aminotransferase
Describe the process of transamination.
Transfer of NH4 by glutamate to other amino acids.
What is the general principle of transamination?
- No loss of gain of N2.
- AA1 + ketoacid 2 to ketoacid 1 + AA2 ( readily reversible process.
- alpha- ketoglutarate also involved
Where is excess glutamate metabolised?
In mitochondria of hepatocytes.
Body protein undergoes constant turnover. True or false?
True
How is nitrogen transported through plasma to liver?
- Glutamine (transports ammonia in blood stream)
- Alanine (glutamate donates ammonia to pyruvate to make alanine)
* Glutamate, alpha-ketogluturate and pyruvate, alanine shuttle occur in muscles and liver).
In the urea cycle, what goes in and what goes out?
Ammonia in and urea out.
How is urea formed?
Nitrogen excreted as ammonia and converted to urea in urea cycle.
What is the function of glutaminase?
Removes nitrogen from glutamine and forms urea in mitochondria.
What are the fates of carbon skeletons?
Converted to glucose or oxidised as part of citric acid cycle ie.
- Glucogenic ( fed into gluconeogenesis)
- Ketogenic (fed into acetoacetate or acetyl CoA)
How many enzymes are in the urea cycle?
Five
How do metabolic defects in the urea cycle give rise to clinical problems?
Wherever there is an enzyme, a clinical disorder can arise e.g most common = ornithine transcarbomylase (OTC) deficiency.
What does OTC cause?
Hyperammonaemia (highly toxic, BBB not protected so medical emergency)
NB: typically presents in newborn period.
What defects in amino acids can exist?
- Decrease enzyme activity
- Decrease product
- Increase precursors
What is PKU?
- absence/deficiency in phenylalanine hydroxyls (PAH)
- autosomal recessive
- increase phenylalanine levels (toxic)
How is PKU diagnosed?
“Guthrie card” (decrease in tyrosine and increase in phenylalanine)
*Phe increases once feeding is established in newborn, day 3-4 = irritability and feeding difficulties arise.
What is the treatment for PKU?
Decrease protein in diet and supplement with tyrosine.
What are the clinical features if untreated?
Impaired brain development, musty odour and neurological features.
Define the major carbohydrates of the diet.
Monosaccharide, Disaccharides and Polysaccharides
Give examples of monosaccharides.
glucose, galactose and fructose
Give examples of disaccharides.
Lactose, maltose and sucrose
Describe the structure of disaccharides.
Formed from two monosaccharides linked by glycosidic bonds (between oH of one monomer and anomeric C of another)
What monosaccharides for lactose?
Glucose and galactose
Give examples of polysaccharides.
Glycogen and starch
Describe the structure of polysaccharides.
- Polymers of medium to high molecular weight composed of long chains of monosaccharides bound by glycosidic bonds.
- Can be linear or highly branched
- Homopolysaccharide or heteropolysaccharide
What is the product of hydrolysed polysaccharides?
Monosaccharides and oligosaccharides
What polysaccharide has the most branches?
Glycogen (branched every 8 residues)
What is starch made of?
2 x glucose monomers which form alpha helices
Describe in outline carbohydrate digestion.
Digestion:
Mouth (amylase) - stomach (no digestion) - duodenum (pancreatic amylase) - jejunum (4 x mucosal cell-surface enzymes) - Glucose, Galactose and Fructose.
What are the four enzymes found in the jejunum?
Isomaltase, glucoamylase, sucrose, lactase
Are alpha1-6 bonds branched or unbranched?
Branched
How is glucose absorbed?
- Na+ drives the process and immediately removed from cell by Na+/K+ pump.
- Glutamate proteins recognise glucose and transport.
- Can move against concentration gradient when blood glucose is high.
Once glucose is absorbed into the blood from the intestinal lumen, where does it travel?
Liver (phosphorylated by hepatocytes into glucose-6-phosphate)
How is galactose absorbed?
Similarly to glucose.
How is fructose absorbed?
Binds to channel protein GLUT5 and moves down concentration gradient from gut lumen to blood.
Describe oligosaccharides and give examples.
They Cann’t be absorbed e.g cellulose and hemicellulose.
Discuss the action of glucokinase.
Phosphorylates glucose and ATP to glucose-6-phosphate and ADP.
Where is glucokinase found?
The liver
Compare Km and Vmax of glucokinase and hexokinase.
Glucokinase = High km and high Vmax Hexokinase = Low Km and Low Vmax
Where is hexokinase found?
In muscle and rest of body.
Discuss the action of hexokinase.
Same as glucokinase (Phosphorylates glucose and ATP to glucose-6-phosphate and ADP
Discuss the mechanism of action of glucokinase.
As substrate concentration increases, increased activity i.e faster turnover.
Discuss the mechanism of action of hexokinase.
Initial reaction faster at lower glucose concentration and will ‘grab’ when concentration increases.
What enzyme responds to varying glucose levels.
Glucokinase
Describe the synthesis of glycogen.
- Glycogenin (covalently binds glucose, from UDP-glucose)
- Forms chains of approximately 8 residues
- Glycogen synthase extends glucose chains
- Chains broken down by glycogen-branching enzyme
- Re-attached by alpha1-6 bonds to give branch points.
Describe the degradation of glycogen.
- Glycogen phosphorylase - removes terminal glucose residues from non-reducing ends to release glucose-1-phosphate
- De-branching enzyme - removes glucose near branch by 2 steps:
a) transferase (removes 3 x Glc residues)
b) glucosidase (removes final Glc)
What is the function of glycogen phosphorylase?
Removes terminal glucose residues from non-reducing ends to release glucose-1-phosphate.
What is McArdle’s syndrome?
Skeletal muscle phosphorylase deficiency, increase muscle glycogen.
What is Von Gierke’s?
Glucose-6-phosphate deficiency, high liver glycogen and low blood glucose.
What is the function of glycogen in muscles?
Energy store, only from muscle.
What is the function of glycogen in the liver?
Maintains blood glucose.
What is the role of glucose-6-phosphatase?
Converts G-6-P to glucose in liver.
Describe glycolysis.
A series of reactions not requiring O2 that splits glucose, glycogen or other carbohydrates into pyruvic or lactic acid while storing a relatively small amount of ATP.
Where does glycolysis occur?
Cytosol
What is the net gain of ATP?
2 x ATP
How many steps are in glycolysis?
10
What are the two main phases of glycolysis?
- Preparatory phase (glucose to fructose-1,6-bisphosphate, 2 x ATP used)
- Pay off phase (G-3-P to pyruvate, 4 x ATP gained)
What co-factor is required throughout glycolysis?
Magnesium
What steps are energy coupled?
Steps 6 and 7 (produced NADH and ATP)
Is glycolysis an exergonic or endergonic?
Highly exergonic.
What enzymes are involved in phosphorylation of glucose at the first stage of glycolysis?
Glucokinase and hexokinase.
When does the pentose phosphate pathway occur?
Between steps 1 and 2 of glycolysis
Give an example of a substrate-level phosphorylation reaction.
Glycolysis
What are the three potential fates of pyruvate?
- 2Acetyl CoA and citric acid cycle
- 2Ethanol + 2CO2 (under hypoxic or anaerobic conditions)
- 2Lactate (under anaerobic conditions- CORI CYCLE)
What enzyme converts pyruvate to 2 x ethanol + 2 x CO2?
Pyruvate decarboxylase
What enzyme converts pyruvate to 2 x Acetyl CoA (aerobic reaction)?
Pyruvate dehydrogenase
What electron carrier is used to produce NADH during the reaction from pyruvate to Acetyl CoA?
NAD+
What enzyme converts pyruvate to 2 x Lactate?
Lactate dehydrogenase
What electron carrier is oxidised to form NAD+ in the reaction of pyruvate to lactate?
NADH + H+
Ingested alcohol reduces which intermediate particularly in the liver?
NAD+
Monomers of carbohydrates are linked together by?
Glycosidic bonds.
Catabolism of 1 mol of glucose to lactate generates how many net moles of ATP?
2
What process forms glucose from 2 x Lactate?
Gluconeogenesis
Where does the cori cycle occur?
Between the liver and muscles (glucose and lactate shuttle)
What are the products of the citric acid cycle?
4CO2 and 4H2O, GTP, NADH and FADH2
What are the three main molecules that produce acetyl coA?
- AA catabolism
- Glycolysis
- Fatty acid oxidation
What is the function of the lactate dehydrogenase reaction?
Converts pyruvate to Lactate while oxidising NADH and H+ to NAD+
What is the function of pyruvate dehydrogenase?
Converts pyruvate to acetyl CoA while reducing NAD+ to NADH.
Under what environment does lactate dehydrogenase work?
Anaerobic
Under what environment does pyruvate dehydrogenase work?
Aerobic
What is the fate of blood lactate?
Lactate is converted in liver to glucose by gluconeogenesis and repays oxygen debt run-up by molecules in the Cori Cycle.
Where does gluconeogenesis occur?
In the liver.
How many reactions of glycolysis are reversible?
7/10, -deltaG prevents other 3 reactions from being reversible.
What is the result of drinking on gluconeogenesis?
Decreases gluconeogenesis.
What electron carrier is required in gluconeogenesis?
NAD+
How are the 3 irreversible reactions of glycolysis side-stepped in gluconeogenesis?
4 reactions catalysed by enzymes
- Pyruvate to Oxaloacetate (pyruvate carboxylase)
- Oxaloacetate to PEP (PEP carboxylase)
- F-1,6-bisphosphate to F-6-P (fructose-1,6-bisphosphatase)
- G-6-P to glucose (glucose-6-phosphatase)
Where does absorbed galactose enter the glycolysis pathway?
At G-6-P.
Where does absorbed fructose enter the glycolysis pathway?
At F-6-P.
Where does the final step in gluconeogenesis to make glucose occur?
In the lumen of ER.
What is the function of the pentose phosphate pathway?
Produces NADPH and pentoses (5-carbon sugars)
What are pentoses?
5 carbon sugars that are precursors of ATP, RNA and DNA.
What are the two phases of the pentose phosphate pathway?
- Oxidative (irreversible)
2. Non-oxidative (reversible)
What are the 5 major lipid classes?
- Fatty acids
- Triacylglycerides
- Phospholipids
- Glycolipids
- Steroids
Describe fatty acids.
Can be unsaturated (one or more double bonds), saturated (no double bonds and high Tm) or essential (linolenic and alpha-linolenic from omega 3 in plants)
What are “good” fatty acids?
High in polyunsaturated fatty acids.
What are “bad” fatty acids?
High in saturated fatty acids.
What are “really bad” fatty acids?
Trans fatty acids
What is the result of deficiencies in essential FAs?
Growth retardation, reproductive failure, skin lesions, reduced omega 3 = ADHD and depression.
Describe triacylglycerides.
- Esters of FAs and glycerol
- water soluble, neutral uncharged
- major lipid component of adipose tissue
Where are triacylglycerides digested?
In SI by pancreatic lipase to monoacylglycerol and two FAs.
Where are triacylglycerides stored?
in adipose tissue as droplets (‘depot fat’).
How are FAs released from stored TAGs in adipose tissue?
Hormone sensitive lipase.
Describe phospholipids.
- Glycerol bounded by two fatty acids and phosphate group.
- Amphipathic
How are phospholipids digested?
By hydrolysis to FA and lysophospholipid.
Describe glycolipid.
Carbohydrate + lipid, important in nerve myelination and blood group antigens.
Describe steroid.
Ring structure e.g cholesterol (cell membrane component, precursor, made in liver)
How are lipids digested?
- Biles salts emulsify dietary fats in the SI and form mixed micelles
- Intestinal lipase degrades TAGs
- FA and breakdown products taken up by intestinal mucosa and converted to TAGs
- TAGs incorporated with cholesterol and apolipoproteins into CHYLOMICRONS.
- Chylomicrons move through lymphatic system and blood to tissues
- Lipoprotein lipase activated by apoC-II in capillary, converts TAG to FA and glycerol.
- FA enters cells and oxidised as fuel or re-esterified for storage.
How are lipids transported?
Free FAs = complex with serum albumin
Most FAs esterified = carried in lipoproteins
What are chylomicrons?
TAG rich, intestine to tissues
Describe VLDL.
Very low density lipoprotein, TAG rich, liver to tissues.
Describe LDL.
Bad. Cholesterol rich to extra hepatic tissues.
Describe HDL.
Good. Protein/cholesterol rich, tissue to liver for elimination.
What is the product of FA synthesis?
Palmitate
What is the building block for FA synthesis?
Malonyl CoA
Where does FA synthesis occur?
Cytosol in liver
What is the inhibitor of FA synthesis?
Long chain fatty acyl CoA
What is the reductant in FA synthesis?
NADP
What carrier protein is used in FA synthesis?
ACP, citrate carrier of acyl/acetyl groups
Describe the steps in FA synthesis.
Condensation - Reduction - Dehydration - Reduction
Define essential FAs.
Ingested from plants. E.g linoleic from prostaglandins and linolenic from omega 3.
What is the function of the citrate shuttle?
When acetyl-CoA accumulates in the mitochondrial matrix (for example, after a big meal), it must be moved to the cytoplasm where it can be used in fatty acid biosynthesis. Acetyl-CoA cannot pass directly through the inner membrane of the mitochondrion, however, and must be shuttled out of the mitochondrion on the back of oxaloacetate (to form citrate).
What is needed fro fatty acid synthesis?
- 8 Acetyl CoA
- 14NADPH (6 from PPP)
- Acetyl CoA carboxylase
- Fatty acid synthase
What is the commitment step in FA synthesis
Formation of Malonyl CoA
Describe the process of FA synthesis from Acetyl CoA to adipose tissue.
Acetyl CoA - (liver)FA - TAG - VLDL - Adipose tissue
Can FAs be converted to glucose?
No
When does beta-oxidation occur?
Starvation
What is beta-oxidation?
Catabolism/ degrades FAs two carbons at a time
Where does beta-oxidation occur?
Mitochondrial matrix in muscle and liver
What are the products of beta-oxidation?
Acetyl CoA, NADH and FADH2
What is the inhibitor of beta-oxidation?
Malonyl CoA
How are long chain fatty acyl CoA in cytoplasm transferred to the mitochondrial matrix?
Carnitine shuttle
What enzymes are required in beta-oxidation?
Carnitine palmitoyl-transferase (CAT-1)
How many ATP molecules are produced during beta-oxidation?
129 ATP
What carrier protein is required in beta-oxidation?
Coenzyme A
What are the steps in beta-oxidation?
Dehydrogenation - hydration - dehydrogenation - thiolysis
When does FA synthesis occur?
After a carbohydrate rich meal.
Describe the structure of cholesterol.
Sterol, ring structure
Where is cholesterol made?
In liver from acetyl CoA
What is the function of cholesterol?
Component of cell membrane and precursors of other substances e.g sterol hormones, fit D, bile salts
What is the function of statins?
Inhibit HMG-CoA reductase (essential in cholesterol synthesis)
When are ketone bodies produced?
During fasting/ starvation (liver flooded with acetyl CoA from fatty acid breakdown)
Describe the synthesis of ketone bodies.
Decrease in glucose, increases acetyl CoA from fat metabolism, converted to ketone bodies for cardiac, skeletal and brain cells which can’t use FAs.
Name 3 ketone bodies.
- Acetoacetate
- Acetone
- Beta-hydroxybuterate
How are ketones transported around the body?
They are water soluble.
There is always a low level of ketone bodies produced by the liver. True or false?
True
Does the liver use ketone bodies?
No the liver makes ketone bodies but doesn’t use them.
What is the result of excessive ketone bodies?
Diabetic ketoacidosis (when insulin absent), ketoemwia, ketonuria and academia results, fruity odour, acidotic
How are ketone bodies transported in blood?
Bound to albumin or lipoprotein.
Define alpha(1-4) linkage.
Glycosidic bond formed by condensation reaction between hydroxy residue on carbon-1 of one monosaccharide and the anomeric carbon-4 on the other monosaccharide. They have LINEAR formation.
Define alpha (1-6) linkage.
BRANCHES in the chains exist. Covalent bond formed between –OH of carbon 1 of one sugar and the –OH of carbon 6 of another sugar. Can be alpha or beta.
Are disaccharides normally present in the urine?
No, the molecules are too big to pass through stomach mucosa. However, if ulcer exists, molecules pass through and not broken down into monomers and released as waste.
Why does farting occur after baked beans (excellent source of plant protein)?
Cellulose and hemicellulose increase faecal bulk and decrease transit time for food to get through the gut. Broken down by gut bacteria yielding CH4 and H2 (where age comes from).
Describe lactose intolerance.
Undigested lactose because membrane lactase enzymes are damaged, the lactose is broken down by gut bacteria (e.g from acute gastroenteritis) causing gas build up and irritant acids. Lactose is osmotically active thus drawing water from the gut into the lumen causing diarrhoea. Enzyme activity returns when gut recovers from gastroeneteritis.
How useful are glucose and FAs to RBCs?
Use glucose to produce lactate and don’t use fatty acids as they don’t have mitochondria. Short lifespan of RBC because of build up of acidity.
How useful are glucose and FAs to skeletal muscle?
Glucose and FAs are both used for fuel. In active muscles, glucose main source as it has large glycogen store and can be converted to glucose-6-phosphate. In resting muscles however, fatty acids are the main energy store.
How useful are glucose and FAs for the brain?
Lacks fuel stores and therefore is provided with a continuous supply of glucose for energy which is mostly used to power transport mechanisms that maintain the Na-K membrane potential. Fatty acids do not provide energy to the brain as they are bound to albumin which cannot cross the BBB. In starvation, ketone bodies produced by the liver replace glucose as fuel for brain.
How is glucose transported into the brain?
Glucose is transported into brain cells by GLUT-3 (has low Km for glucose, therefore saturated most of the time).
What causes “sweet breath”?
Cellulose is broken down by gut flora into volatile fatty acids and not into simple sugars e.g acetic acid which is converted to activated acitate therefore higher amounts of acetyl CoA when it is absorbed, too much in liver, excess transported to muscle etc and formed ketone bodies and exhaled causing the sweet breath
What is brown fat?
Brown fat contains more mitochondria, numerous small lipid droplets (instead of just one found in white fat) and more capillaries
What is the function of brown fat?
It’s primary function is thermoregulation (especially in newborns) as the brown fat produces more energy in the form of heat (ATP) i.e alternative form of heat generation since babaies have a larger ratio of body surface area to body volume, lack of subcutaneous fat, inability to move away from the cold or put on jacket etc. Also the nervous system hasn’t fully developed and therefore, slower to react to cold.
What is the function of white fat?
Stores fat only.
