Carbohydrate Metabolism Flashcards
Carbohydrates
Carbon + hydrogen
Most abundant organic molecule
What are the functions of carbohydrates?
Energy in the diet
Storage in the form of energy
Serving as a component of cell membrane
Monosaccharides
Simple sugars
Those with 3-7 physiological importance
Disaccharides
Sucrose, maltose, lactose
Polysaccharides
Glycogen (animals)
Starch (plants)
Cellulose (only animals can metabolize)
What are the most important monosaccharides?
Glucose, fructose and galactose
Glucose
Major mammalian fuel
Wildly distributed in fruits and veggies as monosaccharides, disaccharides and polysaccharides
Why is glucose converted to other carbs?
For storage during catabolism
What diseases are associated with glucose metabolism?
Diabetes mellitus, galactosemia, glycogen storage disease
Galactosemia
Rare, hereditary disorder
Affects the body’s ability to convert galactose to glucose
Glycogen storage disease
Inability to form or degrade glycogen in normal metabolic pathways
Affects miniature dog breeds, cats, horses and primates
Prognosis is poor
What are the types of glycogen storage disease?
Type 1: G6P deficiency
Type 2 and 3: debranching enzyme deficiency
What are glucose transporters called?
GLUT 1-4
SGLT 1 and 2
SGLT glucose transporter
Located in the apical membrane of cells that line the proximal tubule (kindey) and small intestine
SGLT-1
Moves 2 Na with each glucose
Kidney, small intestine
SGLT3 and SGLT 2
Move one Na for each glucose
Kidney
Cells lacking _______ do not respond to insulin
GLUT-4
How is glucose absorbed?
Na-glucose transporter (absorbed from the lumen)
Hyperglycemia
When the GLUT transporter isn’t working
Have high blood glucose
Where is the GLUT-4 transporter located?
When insulin is present
Heart, skeletal muscles and fat
Glycolysis
Embeden-Meyerhoff Pathway (EMP)
To start removing the energy stored in glucose and make ATP the cell can use
Major route for catabolism of glucose, fructose and galactose
First step for respiration
How much glucose is metabolized via EMP?
80-90%
Glycolysis Process
- GLUCOSE enters the cytoplasm from the blood
- 2 ATP are used to energize the glucose
- GLUCOSE splits in 2
- Two 3-CARBON molecules made
- Each 3 CARBON molecule gives HIGH ENERGY ELECTRONS and HYDROGEN to make NADH
- Each 3 C molecule then gives energy to make 4 ATP molecules (2 each side)
- Each 3 C molecule now becomes a molecule of PYRUVATE (3C)
- NADH carries energy to the MITOCHONDRIA to be used in ELECTRON TRANSPORT
Phosphofructokinase deficiency
Clinical significance of glycolysis
Glycogen storage disorder
Breeds: american cocker spaniels, english springer spaniels
Pyruvate kinase deficiency
Enzyme in the last step of glycolysis that catalyzes the conversion of phophoenolypyruvate in ADP and to pyruvate and ATP in glycolysis
Associated with anemia
Breeds: Basenjis, beagles, cairn terriers, west highland white terriers
Anaerobic glycolysis
Glycolysis when oxygen is unavailable for oxidative phosphorylation
Why is anaerobic glycolysis important
Because the release of glycolytic energy to the cells can be lifesaving measure for a few minutes when oxygen is unavailable
What does the formation of lactic acid during anaerobic glycolysis allow?
The release of extra anaerobic energy
Phosphate Dehydrogenase Deficiency
An inherited metabolic disorder affecting Clumber Spaniels
Affected dogs present signs as early as 15 weeks
PDH deficiency symptoms
Exercise intolerance (no more than 5 mins)
Puppy can’t play along with litter
Walk slowly and rest more often
Collapse during exercise/ play
What is another name for Tricarboxylic Acid (TCA) cycle
Kreb’s cycle
TCA cycle
A major integration center for coordinating carbohydrate, lipid and protein metabolism
Produces 2 ATP
What reactions is TCA cycle involved in?
Transamination, deamination, gluconeogenesis from lactate, animo acids and propionate and lipogenesis in the liver
Where in the cell does TCA cycle occur?
Mitochondrial matrix
TCA ________ are not compatible with life
enzyme deficiences
Oxidative Phosphorylation
Metabolic pathway where cells use enzymes to oxidize nutrients, releasing chemical energy to produce ATP (mitochondria)
What does glycolysis produce
2 net ATP
2 NADHs
2 Pyruvates
What does 1 glucose molecule produce
2 ATP from glycolysis
2 ATP from TCA
10 NADH (2+2+6)= 30 ATP
2 FADH2 from 4 ATP
(34 from oxidative phosphorylation)
Total 36-38 ATP
How many ATPs does NADH produce?
2 ATP
Glucneogenesis
Process wehre non-carbohydrate substrates are converted into Gluc-6-P in the liver and kidneys
A route to clear certain metabolites from blood
Stimulated by diabetogenic hormones
What does gluconeogenesis provide?
Plasma glucose to glucose-sensitve tissues such as nerves and RBCs between meals
What leads to hepatic glycogenesis in omnivores?
High hepatic portal glucose after meals
What happens to omnivores between meals?
Hepatic glycogenolysis and gluconeogenesis will dominate
Hepatic glycogenolysis will provide glucose needs for 12-28 hours
Why do ruminants and strict carnivores rely on Gluconeogenesis?
Little or no glucose is absorbed from GI and liver glycogen reserve is limited
so GNG is a continuous process with little or no correlation to food
Cori cycle
The continuous conversion of lactate from muscle to glucose in liver and back to lactate in muscle
From Gerty and Carl Cori
Dog Glycogen Storage Disease (GSD)
Glucose 2-phosphatase deficiency when circulating blood glucose levels cannot be increased
What is the result of Dog Glycogen Storage Disease?
Fasting hypoglycemia
Accumulation of glycogen and fat (liver and kidney issues)
What does the shunting of G6P into alternative metabolic pathway results in?
Lactic acidosis
Hypertriglyceridemia
Hyperuricemia
How much glucose breakdown is not in glycolysis and citric acid cycle?
30%
What does the pentose phosphate shunt do?
Generate NADPH
Provision of ribose for nucleotide and nucleic acid synthesis
What happens when a muscle is deficient in Gluc-6-P dehydrogenase?
Limited hexo-monophosphate shunt and lipid synthetic activity
What dog has G6P D.H. deficiency been reported in?
Weimaraner dogs
What can G6P D.H. deficiency in humans lead to?
Hemolytic anemia
What does NADPH deficiency lead to?
Impaired GSH reduction and hemoglobin oxidized
What is required for hexo-monophosphate shunt ?
MG ++ and thiamine
What does the oxidative phase of hexo-monophosphate shunt produce
It’s irreversible and produces CO2 and NADPH
What are the biosynthetic functions of the uronic acid pathway
Synthesis of sugar moieties for glycoproteins
Participates in heparin and heparan sulfate formation
Production of UDP-glucoronate for various conjugation reactions
L-ascorbate formation (vitamin c)
Minor route for formation of pentoses that can enter HMS
What enzyme of the uronic acid pathway is absent in humans?
Gulonolacton oxidase because we can’t synthesize that enzyme
Also absent in fish, flying mammals and songbirds
Glucokinase
Enzyme in the liver and pancreatic B cell
Inducible in humans but not in ruminant liver because of low glucose absorbed from GI
Hexokinase
Non-indicible
Present in all mammalian cells
Strongly inhibted by Glc-6-P
Activity in RBC declines with age
Responsible for erythrocyte
What is the fate of glucose?
Glucose to G6P by enzyme glucokinase and hexokinase, and ATP, then back to phosphate
Glycolysis
How is glycogen utilized after absorption into cells?
It’s utilized immediately for energy or stored in the form of glycogen
Glycogenesis
Process of glycogen formation
Glucogenolysis
Process of glycogen breakdown to re-form glucose
What are the features of glycoge storage disease?
Exercise intolerance, low blood glucose, hyperlipidemia, ketonemia
GSD: G6P deficiency
Toy dog breeds
GSD: 1,4-glucosidase, acid maltase deficiency
Corriedale sheep, lapland dogs, shorthorn and brashman cattle, japanese quail
GSD debranching deficiency
German shepherds
GSD branch deficiency
Cat, charolaise cattle, quarter horses
GSD: phosphofructokinase deficiency
Egnlish spring spaniels, wachtelhunds
