Carbohydrate metabolism

Function of carbohydrate

Energy in diet

Storage form of energy

Component of cell membrane & DNA

Monosaccharides

Simple sugars; 3-7C/mol are of most physiological importance - glucose being the most readily absorbed

Disaccharides

Sucrose, lactose, maltose

Broken down into simple sugars

Polysaccharides

Complex sugars

Glycogen - animals

Startch & cellulose - plants

Glucose

Major fuel source; converted to other carbsD

Diseases associated with glucose metabolism

Diabetes mellitus, galactosemia, glycogen storage disease

Glucose transporters

Found throughout the body; transport glucose into the cell; type dependent on cell type

GLUT 4

Insulin dependent glucose transporter; found in the heart, skeletal muscle, and fat

Sodium Glucose Cotransportor (SGLT)

Located in apical membrane of cells lining proximal tubule and small intestines; moves sodium with glucose

SGLT-1

Moves 2 Na+ per glucose

SGLT-2 & SGLT-3

Move 1 Na+ per glucose

Where is glucose first transported?

Liver; to be converted to glycogen

Glycogen pathway

Glycogen > glucose -1-phosephate > glucose-6-phosphate > glycolysis

Glucose-1-phosphate pathway

Glucose -1-phosphate > uridine diphosphate glucose > glycogen

Blood glucose pathway

Blood > glucokinase > glucose-6-phosphate > glycolysis

Glucose-6-phosphate pathway

Glucose-6-phosphate > phosphatase > blood - blood glucose

Embden-Meyerhoff Pathway (EMP)

Scientific credit for glycolysis; same cycle

Major route for catabolism of gluc., fruct., & galac.

How much glucose is metabolized via glycolysis?

80-90%; the remainder is used to produce other molecules (DNA,RNA)

Tricarboxlylic Acid Cycle (TCA/Kreb’s)

Major integration center for coordinating carbohydrate, lipid, and protein metabolism

Transamination

the process of transferring one amino group from an amino acid to a keto acid

Deamination

the removal of an amino group from an amino acid or other compound

Gluconeogenesis

non-carbohydrate precursors are converted into glucose by the liver and kidneys to maintain blood sugar levels, especially during fasting or exercise

Where does gluconeogenesis occur

Liver; mitrochondrial matrix

Why are TCA deficiencies not compatible with life?

lack of ATP production will cause the body to rely only on glycolysis, producing only 2 ATP in comparison to 32 in aerobic glucose metabolism

How many conversions occur in the Kreb’s cycle?

8

Acetyl-CoA is converted to

Citrate via citrate synthase

Citrate is converted to

Isocitrate via aconitase

Isotrate is converted to

alpha-ketogluterate via Isocitrate dehyrdrogenase

Alpha-ketogluterate is converted to

Succiyl-CoA via Alpha-KG dehydrogenase

Succinyl-CoA is converted to

Succinate via Succinate Thiokinase

Succinate is converted to

Fumerate via succinate dehydrogenase

Fumarate is converted to

Malate via Fumerase

Malate is converted to

Oxaloacetate via malate dehydrogenase

Where is Oxaloacetate derrived from?

Pyruvate, during glucolysis

Role of oxidative phosphorylation

O2 acts as a e- acceptor, to continue the production of ATP

What happes to CO2 released from the TCA cycle?

Combines with bicarbonate to maintain pH

How is Oxidative phosporylation powered?

An electron is sent from the TCA cycle to power the conversion.

Total number of ATP generated from 1 glucose molecule

38 mole ATP

2 from glycolysis

2 from citric acid cycle

34 from oxidative phosphorylation

Glycogen

Fasting energy reserve, followed by fat and protein

Hyperglycermia

Too much glucose within the blood

Hypoglycemia

Too little glucose in the blood; body mechanisms cannot be maintained

Gluconeogenesis clears which metabolites from the blood?

Lactate in RBC & muscle cells

What is gluconeogenesis stimulated by?

Diabetogenic hormones - ephinepherine, nonepinepherine, glucogon

Where is glucogon secreted?

pancreas

How does glucogenesis vary by species

Omnivores hepatic glycogenolysis can provde from 12-28 hours

Ruminant & carnivorse rely exclusively on gluconeogenesis with no correlation with food intake

How does gluconeogenesis utilize glycolysis?

Is the reverse of glycolysis and TCA cycles; energy consuming

Why is the conversion of Pyruvate to oxaloacetate non-reversable?

Driven by pyruvatte carboxylase, and PEP carbodykinase; Kinase driven reactions are often non-reverable

The Cori Cycle

The continuous conversion of lactate (mm) > glucose (liver) > lactate (mm)

Lactate is converted to

Pyruvate via lactate dehydrogenase

Dog glycogen storage disease (GDS)

G6Pase deficiency

Blood glucose cannot be raised

Accumulation of glycogen & fat w/i the liver

Shuntin gof G6P into alt. metabolic pathways > lactic acidosis, hypertriglyceridemia & hyperuricemia

Pentose phosphate shunt

up 30% of glucose broken down via this pathway

independent of glycolysis & CAC

Removes 1 carbon to produce CO2 and H+

H+ is sent to Oxidative phos. pathway > ATP

Alt. mechanism for glucose utilization when facing enzymatic abnormalities

What is the main ribose pathway from DNA,RNA, and protein synthesis?

D-Ribose-5-Phosphate

Pentose Phosphate Pathway Equation

Glucose + 12NADP+ + 6H2O = 6CO2 + 12H + 12 NADPH

Function of NADPH

Synthesis of lipids, protein, hormones; GSH production in RBC, lens, and cornea

Ribose function

Nucleotide/nucleic acid synthesis

Where is the Pentose phosphate pathway the most active?

Liver and adipose tissue - does not produce ATP

Hexose Monophosphate Shunt (HMS)

Muscle deficient in G6P dehydrogenase, limiting HMS and lipid synthesis

Deficiency of enzyme common in Weimaraners

IN humans, leads to hemolytic anemia

Uronic Acid Pathway

1. synthesis of sugat moieties for glycoproteins

2. participate in heparin and heparan sultfate formation

3. produce UDP-glucoronate for various conjugation rxn

4. L-ascorbate (vit. c) formation

5. Minor route for formation of pentoses

Does not produce ATP

Glucokinase

Inducible - liver and pancreatic beta-cell specific

Non-inducible in ruminant liver due to low glucose absorption from GI

Hexokinase

Non-inducible

Present in all mammal cells

strongly inhibited by Glc-6-P

activity in RBC declines with age

Respnsible for erthrocyte turnover

Fate of glucose

Glucose > glucokinase (hexokinase) + ATP > Glc-6-P > Glycogen or glycolysis

Formation of Glycogen

large glucose polymer; glycogenesis

glycogenolysis

glycogen breakdown to re-form glucose; not the reverse of glycogenesis

GSD

Inability to form/degrade glycogen in normal metabolic pathways

Affects miniature breed dogs, cats,horses, and primates

many types - I (Glc-6-P deficiency; II- debranching enzyme deficiency)

Manifest as exercise intolerance

Poor prognosis